1. health and fitness
2. disease
3. cancer

September 2012 — Special Issue: Proceedings of the Global Congress on Prostate Cancer
ISSN: 2034-8393
Prostate cancer
From diagnosis to managing
advanced disease
Proceedings of the Global Congress on Prostate Cancer
28-30 June 2012 – Brussels, Belgium
Guest editors
Alex Mottrie, OLV Clinic, Aalst, Belgium
Bertrand Tombal, University Hospital Saint-Luc, Brussels, Belgium
Hein Van Poppel, University Hospitals Leuven, Leuven, Belgium
Gert De Meerleer, Gent University Hospital, Ghent, Belgium
Prostate cancer
From diagnosis to managing
advanced disease
Proceedings of the Global Congress on Prostate Cancer
28-30 June 2012 – Brussels, Belgium
Highlights
Global Congress on Prostate Cancer
Multiple mirrors for better management
28-30 June 2012, Brussels, Belgium
Abstract
Prostate cancer is one of the most important medical problems in older males. It is the most common cancer and the third deadliest cancer
for men in the European Union and the USA, with 323,790 and 186,320 new cases, respectively and 71,027 and 28,660 deaths in 2008 1.
From 28-30 June 2012, a multidisciplinary faculty of almost 50 urologists, radiologists, radiotherapists, medical oncologists and nuclear
medicine specialists gathered in Brussels, Belgium for the Global Congress on Prostate Cancer to discuss state-of-the art diagnosis and
treatment of patients with localised, high-risk non-metastatic (locally advanced), metastatic and metastatic-castration resistant prostate
cancer. Topics covered were:
• screening
• how to improve the current strategy of prostate biopsy decision making
• how to manage patients with localised prostate cancer at low-, intermediate- or high risk of progression taking into account
treatment options such as active surveillance, radical prostatectomy, radiotherapy and brachytherapy
• how to manage patients with locally advanced prostate cancer
• who should have a lymph node dissection and to which extent
• how to manage unfavourable outcomes after radical prostatectomy and recurrence following initial (radical) therapy
• how to treat metastatic castration-resistant prostate cancer anno 2012
• the role of biomarkers and imaging techniques in prostate cancer diagnosis and follow-up
The current issue of the Mirrors of Medicine journal provides the highlights of this congress, also in perspective of the 2012 guidelines of
the European Association of Urology and the American National Comprehensive Cancer Network. In addition, it contains the abstracts
presented at this congress.
Guest editors
Alex Mottrie, OLV Clinic, Aalst, Belgium
Bertrand Tombal, University Hospital Saint-Luc, Brussels, Belgium
Hein Van Poppel, University Hospitals Leuven, Leuven, Belgium
Gert De Meerleer, Gent University Hospital, Ghent, Belgium
Screening for prostate cancer should be
based on individual risk stratification
balancing its benefits and harms
For each prevented PCa
death
Prostate cancer (PCa) is one of the most important medical
problems in older males. It is the most common cancer and the
third deadliest cancer for men in the European Union and the
Less then one man becomes
incontinent
USA, with 323,790 and 186,320 new cases, respectively and
71,027 and 28,660 deaths in 20081 . It is now well known that
more men die with PCa than from PCa and that many cancers are
indolent/insignificant because they are unlikely to impact on the
And 4 more men suffer from
erectile dysfunction
patient’s health status and survival. The goal of early diagnosis is
to detect threatening/significant cancer at a stage when it is still
curable, and to avoid as much as possible the detection of indolent
cancers. As patients with curable threatening disease usually have
not yet developed symptoms, early detection depends on finding
Figure 1. Screening for prostate cancer (PCa) should balance the risk of death due
to PCa and the risk of suffering from (major) complications or side effects during
remaining life-time8
significant cancer in prostate biopsy (Bx) specimens.
Screening is a strategy used to detect a disease in individuals without
signs or symptoms of that disease. PCa screening is performed by
serum prostate-specific antigen (PSA) measurements and digital
rectal examination (DRE). It aims to decrease PCa-specific mortality
(CSM) but the benefits of screening should be balanced against
the potential harms. These include anxiety of the patient and his
family, complications related to Bx, over-diagnosis of insignificant
PCa (as screen/PSA-detected cancers will not lead to symptoms in
17-50% of men due to the long lead-time of around 10 years2,3 or
more specifically 12.3 years in a 55-year old and 6 years in a 75-year
old man4), and over-treatment of insignificant PCa with radical
therapy and its associated complications such a erectile dysfunction
(ED), urinary incontinence (UI) and bowel dysfunction. Of the 3
major screening trials, i.e. the PLCO (Prostate, Lung, Colorectal
and Ovarian)5, ERSPC (European Randomized Study of Screening
for Prostate Cancer) 6 and the Göteborg7 study, the ERSPC and
Göteborg study have shown that screening decreases CSM (by 21%
in the 11-year follow-up of the ERSPC and by 44% after 14 years
Therefore, it is not the question if we should screen but rather how
and who we should screen. Currently most urological guidelines do
not recommend population screening for PCa. Opportunistic or
individual case-finding based on the subject’s risk profile should,
however, be offered to the well-informed man. Risk stratification
is usually based on the subject’s age (or actually life expectancy),
his family history of PCa, DRE outcome, the serum total PSA
(tPSA) level and prostate volume. Several risk calculators,
nomograms and decision support tools are available for this
purpose. One example is the risk calculator based on the ERSPC
trial, which includes DRE, PSA and prostate volume and indicates
the risk of having (significant: Gleason sum ≥ 7 and ≥ stage T2b)
PCa and whether or not a Bx would be recommended 9 . This is
available at http://www.prostatecancer-riskcalculator.com/sevenprostate-cancer-risk-calculators. Similarly, a Bx decision support
model based on the combined recommendations of 12 European
urologists 10 which also takes into account life expectancy is
available at http://mirrorsofmedicine.org.
of follow-up in the Göteborg study) but that the harms cannot be
neglected. For every PCa death prevented, there will be almost 1
man suffering from UI and 4 men from ED (Figure 1) 8 .
4
4highlights
highlights
Incorporating biomarkers and/or imaging
techniques in individual risk stratification
may be the future for identifying significant
prostate cancer
Unfortunately both serum tPSA and DRE have a low positive and
negative predictive value (PPV, NPV), leading to an increased rate
of repeat Bx for men with a persisting elevated PSA after a first
negative Bx. Therefore, there is a great demand for alternative
or additional biomarkers and/or better imaging techniques than
transrectal ultrasound (TRUS) to better identify pre-Bx those men
at high risk of having clinically significant PCa.
Figure 2. At a PCA3 Score cut-off of 25, 50% of repeat biopsy (Bx) could have been
avoided, while missing 2% of Gleason sum ≥ 7 cancers11
Prostate CAncer gene 3
The Prostate CAncer gene 3 (PCA3) urine test is superior to tPSA,
and %free PSA (%fPSA) in detecting PCa in men with an elevated
Prostate-specific antigen Prostate Health Index
PSA, as it shows slight but significant increases in the area under
the curve (AUC) for positive Bx 3 . According to the 2012 guidelines
The PSA Prostate Health Index (phi) is a serum marker which
of the European Association of Urology (EAU), the main current
interprets tPSA, fPSA and [-2]proPSA or p2PSA in one value:
indication of the PCA3 urine test may be to determine whether
(p2PSA/fPSA)x√tPSA. As such it increases, compared to tPSA, the
a man needs a repeat Bx, but its cost-effectiveness remains to be
AUC18 , specificity (to 65% at fixed sensitivity of 89%) and NPV (to
shown . The Food and Drug Administration (FDA) has approved
89% at fixed sensitivity of 89%)19. At a fixed sensitivity of 90%
in February 2012 PCA3 as an additional tool to guide repeat Bx
or 95%, it also misses least Gleason sum ≥ 7 cancers in the Bx
decisions. Although a cut-off of 35 seems to provide the best
(Table 1)20.
3
balance between sensitivity and specificity, lower cut-offs such as
25, put forward by the FDA, will increase the test’s NPV to 90%
and decrease the chance of missing clinically significant PCa .
11
Table 1. In a biopsy (Bx) study including 322 men, PSA phi at a fixed sensitivity of
90-95% missed, compared with other biomarkers, least Gleason sum ≥ 720
In the US study which formed the basis for FDA approval, 50% of
Sensitivity cut-off
466 repeat Bx could have been avoided at a cut-off of 25, while only
95%
No. with Bx Gleason sum ≥ 7
90%
Missed
Detected
missing 2% of Gleason sum ≥ 7 cancers (Figure 2)11. In a European
tPSA (ng/mL)
2.56
2.93
4
6
51
49
first Bx study, 40% of Bx could have been avoided, while only 2%
%fPSA
28.10
22.95
1
2
54
53
of Gleason sum ≥ 7 cancers would have been missed at a cut-off
%p2PSA
0.91
1.05
1
1
54
54
of 20 . Several studies which compared the PCA3 Score with
phi
19.43
22.49
1
1
54
54
radical prostatectomy (RP) specimen pathology indicated that the
fPSA; free prostate-specific antigen; p2PSA: [-2]proPSA; phi: prostate health index;
tPSA: total prostate-specific antigen
12
PCA3 Score correlates with tumour volume 13-16 or extracapsular
extension (ECE)17 but so far this remains controversial.
In 350 patients with localised PCa who underwent RP, PSA phi
levels were significantly higher in patients with pT3 disease,
pathological Gleason sum ≥ 7 and Gleason sum upgrading, and
significantly lower in patients with tumour volume < 0.5 cc 21 .
As such it could easily replace tPSA for better identifying and
selecting men who need a Bx because they are at risk of having
clinically significant PCa. The EAU 2012 guidelines have not yet
assessed PSA phi 3 .
highlights highlights
5
Prostate HistoScanning and multiparametric
magnetic resonance imaging
As ultrasound (US) has a very low resolution, it cannot be used to
reliably detect PCa. Therefore, there is more and more interest in
using alternative imaging techniques such as Prostate HistoScanning
(PHS) and multiparametric magnetic resonance imaging (mpMRI).
PHS is a computer-aided interpretation of prostate 3-dimensional
(3D) US scans. PHS uses unconverted radiofrequency signals
from the US probe that form a distinctive acoustic signature
(due to high tissue vascularisation, variable elasticity, etc),
which allows the software to distinguish non-malignant from
malignant tissue. Malignant tissue is indicated by a red signal
and total HistoScanning tumour volume (THV) is automatically
calculated. Results of PHS studies have so far been reported in
Figure 3. The median Apparent Diffusion Coefficient (ADC) decreases with
increasing Gleason grade/sum
3 full publications 22-24 and several abstracts but the number of
involved patients was limited. In RP specimen pathology studies
The EAU 2012 guidelines indicate that if clinical suspicion for PCa
most tumours at RP were also discovered by PHS . PHS showed
persists in spite of a negative Bx, MRI may be used to investigate
good sensitivity (90%) and NPV (82%) for detecting foci ≥ 0.20 cc.
the possibility of an anterior located PCa, followed by TRUS- or
This increased with tumour stage, grade and volume . In the
MRI-guided Bx targeted to the suspicious area 3 . This is in line with
few Bx studies performed, THV was significantly higher in those
the European Society of Urogenital Radiology (ESUR) guidelines27.
with a positive compared to a negative Bx and it increased with
However, the general use of mpMRI and mpMRI-guided Bx is
the percentage of positive Bx 26 . Future developments will focus
not (yet) recommended 28 . If MRI-guided Bx is used, T2W-MRI
24
25
on PHS-guided Bx and differentiating compression-induced
is sufficient for imaging of the anterior part of the prostate/
tissue density by the probe from malignant tissue. The EAU 2012
transition zone, whereas DW-MRI is better for imaging of the
guidelines have not yet assessed PHS and more studies involving
posterior part of the prostate: AUC is increased from 0.77 with
larger patient numbers are required to establish its value 3 .
T2W to 0.84 with the combination of T2W and DW-MRI 29.
mpMRI combines anatomical/morphological and functional data.
When only anatomical evaluation is required, T2-weighted (T2W)
MRI is sufficient. Diffusion-weighted MRI (DW-MRI) enables
evaluation of tissue cellularity, dynamic contrast-enhanced
MRI (DCE-MRI) evaluation of angiogenesis and spectroscopic
MRI (S-MRI), which is not routinely performed, evaluation of
tissue metabolic activity. Several studies have demonstrated that
the median Apparent Diffusion Coefficient (ADC) at DW-MRI
correlates very well with tumour grade, also in the transition
zone when S-MRI is used. In a meta-analysis, the NPV of mpMR
ranged between 65-97%. MRI-guided Bx is capable of locating
focal spots and significant/high-grade PCa, i.e. differentiating
Gleason grade 3 from 4/5. The median ADC value also decreases
when Gleason grade/sum increases (Figure 3).
Summary box screening and risk
stratification
• Screening decreases CSM but the rate of reduction
varies between studies
• The benefits of screening need to be balanced against
the associated harms
• Based on current evidence most urological guidelines
do not recommend population-based screening for PCa.
However, opportunistic or individual screening should
be offered to the well-informed man
• Screening should be risk-based. Nomograms, risk
calculators and decision support tools, such as the
ERSPC risk calculator and the MiMe Bx decision
support tool, may aid in identifying patients needing a
Bx and cancers that are likely to be clinically significant
• Incorporating biomarkers such as PCA3 and PSA phi
and imaging techniques such as PHS and MRI may
better identify clinically significant PCa in the (near)
future
6
6highlights
highlights
It is questionable whether Gleason 3+3,
and perhaps even Gleason 3+4, represents
significant prostate cancer with metastatic
potential and it may therefore be renamed to
reduce patient anxiety
It is questionable whether Gleason 3+3, and perhaps even Gleason
When analysing Bx specimens, the pathologist in first instance
point of view, it may therefore be advisable to rename low-grade
determines whether they contain non-malignant (benign
(3+3) PCa.
3+4, represents significant PCa with metastatic potential. This is
related to the fact that of 12,000 patients with Gleason sum 6
aged 60-69 years, the 20-year CSM after RP is ≤ 0.2% (despite
significant PSA relapse) (Figure 5)34 . Only 3 out of 9,557 patients
with localised pathological Gleason sum ≤ 6 cancer died of PCa. In
addition, 100 men with low-risk PCa need to be treated to prevent
one death from the disease. From a patient (and family) anxiety
prostatic hyperplasia, atrophy or inflammation), isolated high0
.2
.6 .4
Death Rate
.8
1
0
1
.8
.2
.2
0
.6 .4
Death Rate
.8
1
.2
0
1
.2
.6 .4
Death Rate
.8
1
0
.2
.8
5
0
.2
.6 .4
Death Rate
.8
.2
1
0
1
5
20
20
0
.6 .4 .2
Death Rate
.8
1
0
1
.8
.8
.2
0
10
15
Years after surgery
Survival
.4 .6
.2
10
15
Years after surgery
.2
.6 .4
Death Rate
5
0
0
1
0
20
Age 70-79, Gleason 8
.8
.2
.8
1
.6 .4
Death Rate
20
15
.8
.8
0
.2
1
0
20
Survival
.4 .6
1
.8
15
10
Years after surgery
Survival
.4
.6
.2
10
15
Years after surgery
20
Age 70-79, Gleason 4+3
.6 .4
Death Rate
5
10
15
Years after surgery
Survival
.4 .6
.2
.6 .4
Death Rate
.8
.2
0
.8
1
0
20
Age 60-69, Gleason 8
Survival
.4 .6
10
Years after surgery
10
15
Years after surgery
1
0
.8
0
0
20
.2
5
Survival
.4 .6
1
.8
0
1
.8
5
Age <60, Gleason 8
0
5
Age 70-79, Gleason 3+4
.8
.2
10
15
Years after surgery
1
.6 .4
Death Rate
5
0
20
Survival
.4 .6
1
.8
Survival
.4 .6
.2
0
0
10
15
Years after surgery
Age 60-69, Gleason 4+3
0
Gleason sum is currently 6 (3+3). Patterns 4 and 5 must be considered
0
20
Age <60, Gleason 4+3
in PCa. The modified Gleason grading system, which was introduced
and does no longer contain patterns 1 and 2. Therefore, the lowest
5
Survival
.4 .6
.2
10
15
Years after surgery
0
.6 .4
Death Rate
5
1
Survival
.4 .6
0
referred to as PINATYP), the risk of PCa is increased to 53% and
in 200531, puts more emphasis on the primary/predominant pattern
0
Age 60-69, Gleason 3+4
.2
with multifocal HGPIN. If HGPIN is accompanied by ASAP (also
The Gleason grade/sum is an important factor for risk stratification
0
20
Age <60, Gleason 3+4
3 years in men with unifocal HGPIN and within 1 year in men
early repeat Bx is recommended 30.
.8
.2
10
15
Years after surgery
1
.6 .4
Death Rate
5
Survival
.4 .6
1
.8
Survival
.4 .6
.2
0
0
Therefore, it is recommended to perform repeat Bx between 1 and
0
greater if HGPIN is found in 4 cores as compared to only 1 core.
1
HGPIN, the risk of having PCa is about 30%. The risk is 2.6 fold
Age 70-79, Gleason 6
Age 60-69, Gleason 6
0
Age <60, Gleason 6
.8
acinar proliferation (ASAP) or malignant cells. In men with
1
grade prostatic intraepithelial neoplasia (HGPIN), atypical small
0
5
10
Years after surgery
15
20
even if the extent is minimal (Figure 4). In high-grade cancer, the
low-grade pattern can be ignored if < 5% (Figure 4). The modified
Gleason grading system has led to considerable grade migration in
43% of Bx, with a higher grade in 31% and a lower grade in 12% 32 ,
and a better correlation between Bx and RP grading (from 58% to
72%) . This also implies that nowadays a Gleason 3+4 probably
Figure 5. Long-term prostate cancer-specific mortality (CSM) in men with
Gleason 6 following radical prostatectomy is very low. Reproduced from Eggener
SE, et al.34, with permission from Elsevier Limited
Black area: CSM; grey area: mortality from competing causes
33
has the same biological characteristics as a Gleason 3+3 and that
3 risk categories can be identified: Gleason sum 6, Gleason sum 7
and Gleason sum 8-10 .
3
Even more important than Gleason grade/sum for PCa risk
stratification (i.e. pathological stage pT3 with ECE and/or seminal
vesicle invasion [SVI]) is tumour volume, which is represented
in the Bx by e.g. the number or fraction/% of positive cores 35 .
Bilateral PCa, Gleason 8-10, number/% of positive cores and
intraprostatic perineural invasion are predictive of pT3 vs. pT2
disease 35.
A recent analysis of the ERSPC, which used the specimens of
325 patients undergoing a RP, confirmed that the threshold
for insignificant PCa for the index tumour volume is 0.55 cc 36 .
However, in those with Gleason sum 6, pT2 tumours, the
threshold for the index tumour volume increases to 1.3 cc and
for total tumour volume to 2.5 cc. These are volumes which can
easily be picked up with imaging techniques such as PHS and MRI.
Therefore, in the future, insignificant PCa may be the tumour that
Figure 4. Modified Gleason grading system of 2005 has led to grade migration
31
highlights highlights
cannot be identified with modern imaging techniques.
7
Pre-treatment disease progression risk
stratification based on the D’Amico criteria is
useful for taking treatment decisions
Active surveillance is a valid treatment
option for men with localised low-risk
prostate cancer
Nowadays the risk stratification system developed by D’Amico
One way to reduce the impact of over-diagnosis and to reduce
and co-workers in 1998 still forms the basis to stratify the risk
morbidity associated with over-treatment is the use of active
of disease progression in patients diagnosed with PCa and guide
surveillance (AS) in selected patients with PCa. AS involves
treatment decision. Identification of patients at low, intermediate
active monitoring of the disease course, with the expectation to
or high risk of progression is based on clinical stage, tPSA and
intervene if the cancer progresses 3 . The treatment options are
37
the Gleason sum (at Bx histology) (Table 2). The D’Amico risk
intended to be curative. This is a completely different approach
stratification system has been adopted by the American Urological
than watchful waiting, which was used in the past/pre-PSA era to
Association (AUA). The EAU and National Comprehensive Cancer
wait with palliative treatment until the development of local or
Network (NCCN) have slightly adapted the criteria and also
systemic progression 3 . AS is currently more and more accepted as
identify a very low-risk and very high-risk category (Table 2).
an appropriate treatment choice in men with localised PCa who are
All or some of the Epstein criteria (T1c, PSA density [PSAD]
at low-risk of progression, e.g. those with a Gleason 6 and a tPSA
< 0.15 ng/‌mL/g, < 3 positive cores and < 50% of cancer in a positive
< 10 ng/mL (Table 2). The EAU 2012 guidelines recommend AS for
core)38 are used to identify very low-risk PCa (Table 2). In addition,
patients with T1c-T2a cancer and most other characteristics of
whereas in the D’Amico classification system a cT2c belongs to the
very low-risk PCa: tPSA ≤ 10 ng/mL, Gleason sum 6, ≤ 2 positive
high-risk category, in the EAU and NCCN guidelines the cancer
Bx (out of 10), with ≤ 50% of cancer involvement per positive
needs to have extended the prostatic capsule (i.e. cT3a, previously
core 3 . The NCCN 2012 guidelines consider AS a treatment option
called locally advanced PCa) and they categorize patients with SVI
for patients with very low-risk PCa and a life expectancy < 20
or invasion in other tissues adjacent to the prostate (T3b-T4) as
years or with low-risk PCa and a life expectancy < 10 years 4 .
very high-risk PCa. Nowadays, around 30-40% of patients can be
But perhaps it may be better to integrate comorbidity (Charlson
categorized as having (very) low-risk PCa and still around 20%
score) instead of life expectancy into treatment decision. A recent
of patients, even in screened populations, have high-risk PCa 39,40.
analysis of 19,639 patients > 65 years from the US Surveillance,
Epidemiology and End Results (SEER) Medicare database not
Table 2. Biopsy-based definitions to identify pre-treatment the risk of progression
and related treatment choice in patients diagnosed with prostate cancer
Variable
Very
Low-risk
low-risk
(Epstein38/ (D’Amico37/ Intermediate- Intermediaterisk
High-risk
EAU3/
EAU3/
risk (EAU3/
(D’Amico)37
(D’Amico)37
NCCN4)
NCCN4)
NCCN4)
given curative treatment shows that most men with a Charlson
index ≥ 2 (meaning 2 or more comorbidities) will have died from
competing causes of death at 10 years, in particular those with
HighVery
high-risk
risk
(EAU3/
(EAU3/
NCCN4)c NCCN4)
Clinical
stage
T1ca
AND
T1c-T2a
AND
T2b
OR
T2b-T2c
OR
T2c
OR
T3a
OR
tPSA:
ng/‌mL
< 10
AND
< 10
AND
10-20
OR
10-20
OR
> 20
OR
> 20
OR
PSAD:
ng/‌mL/g
< 0.15b
AND
Gleason
sum
≤ 6
AND
≤ 6
7
7
8-10
8-10
Number
of
positive
cores
< 3
(out of 6)
AND
Cancer
volume/
core
< 50%
low-grade PCa (Figure 6)41. As alternative to the Charlson index,
the re-weighted index developed by Daskivich et al. may be used42 .
T3b-T4
EAU: European Association of Urology 2012 guidelines; NCCN: National Comprehensive Cancer Network 2012
guidelines; PSAD: PSA density; tPSA: total prostate-specific antigen
a: T1c-T2a for EAU 2012 guidelines; b: not indicated in the EAU 2012 guidelines;
c: in the past this was referred to as “locally advanced” disease
Figure 6. In men with T1c prostate cancer (PCa), comorbidity (Charlson index ≥ 2)
has a strong impact on 10-year overall mortality, in particular in patients with
low-grade (Gleason sum 5-7) PCa. PCa-specific mortality is mainly influenced by
tumour grade/Gleason sum41
8
8highlights
highlights
In low-risk patients treated with AS, the 10-year PCa-specific
According to the Toronto protocol, patients on AS need to have
survival (CSS) was 97% with 62% still alive on AS after 10 years .
a confirmatory Bx within 9-12 months. Thereafter, repeat Bx is
Although RP may, according to a Scandinavian trial, be associated
indicated every 3-5 years up to the age of 80 years. The schedule
with reduced CSM compared with watchful waiting (Figure 7) ,
for repeat Bx should be weighed against the associated burden
there appears to be no difference in CSM when data of AS in low-
of complications, infection (potentially resulting in sepsis and
risk patients are superimposed on those in the RP vs. watchful
hospitalization) and RP becoming technically more challenging
waiting trial (Figure 7)45. There is no indication for an increase in
after multiple sets of Bx. If the PSA doubling time (DT) is < 3 years
anxiety or depression in patients receiving watchful waiting vs.
or when there is an increase in cancer volume or a minor element
those receiving RP46 .
of Gleason 4 in the Bx, mpMRI (specifically targeting the anterior
43
44
43
part of the prostate) may be indicated. The NCCN 2012 guidelines
recommend treatment at these occurrences4 . Alternatively, radical
therapy may be initiated if the Bx shows Gleason grade 4 (also
recommended by the EAU 2012 guidelines 3) or an unequivocal
lesion > 10 mm on mpMRI.
In low-risk patients treated with AS and a median follow-up of 6.8
years, 30% of patients received radical therapy because of higher
risk reclassification, i.e. PSA DT < 3 years, Gleason 4+3 and > 50%
increase in cancer volume43 . It should however be noted that there
is no evidence that a PSA DT < 3 years is predictive of adverse Bx or
RP pathology outcome47; it is only a trigger for mpMRI.
Figure 7. Superimposing data with active surveillance in low-risk patients
indicates no increased prostate cancer-specific mortality compared with radical
prostectomy. Reproduced from Klotz L, Thompson I45, with permission from the
Massachusetts Medical Society
The optimal timing for follow-up (based on tPSA, DRE and, most
importantly, repeat Bx) in patients receiving AS is still unclear 3 .
The EAU guidelines 2012 indicate that follow-up should be yearly
or every 2 years3 . In addition, there are several protocols available
(Table 3).
Summary box Gleason grading and
management of localised prostate
cancer with active surveillance
• The modified Gleason grading system of 2005 has
induced considerable grade migration, in particular to
higher Gleason grades/sums
• It is questionable whether Gleason 3+3, and perhaps
even 3+4, represents significant PCa with metastatic
potential
• AS seems to be an appropriate treatment option
for men at (very) low-risk of progression, i.e. those
Table 3. Different protocols for follow-up during active surveillance
Group
tPSA
DRE
Bx
Other
Toronto
Every 3 mo for 2 yrs,
then every 6 mo
Every 6 mo for 2 yrs,
then every 6-12 mo
Within 9-12 mo,
then every 3-5 yrs
up to the age of 80
MRI if PSA DT < 3 yrs
or volume increase
or Gleason 3+4
Canary
Every 6 mo
Every 6-12 mo
At 18 mo,
then every 1-3 yrs
Hopkins
Every 6 mo
Every 6 mo
Every yr
up to the age of 75
NCCN4
Every 6 mo
Every 12 mo
Every 12 mo
with Gleason 6 and a tPSA ≤ 10 ng/mL, and this
also depends on tumour volume in the Bx and life
expectancy/comorbidity (Charlson index)
• Follow-up during AS should be based on the tPSA,
DRE and most importantly repeat Bx. The optimal
timing (yearly or every 2 years) is still unclear. Grade
MRI for all patients
progression in the Bx (Gleason grade 4) could be a
trigger for starting active treatment
Bx: prostate biopsy; DRE: digital rectal examination; mo: months; MRI: magnetic resonance imaging;
(t)PSA (DT): (total) prostate-specific antigen (doubling time); yr(s): year(s)
highlights highlights
9
In patients with localised disease, radical
prostatectomy performs reasonably well
with regard to prostate cancer-specific
mortality: after 15 years, only 19% of high-risk
patients have died from prostate cancer
Biochemical recurrence (BCR)/PSA relapse does not adequately
predict clinical events. Although 30-50% of patients have PSA
relapse after RP, overall survival (OS) and CSS in patients treated
in the PSA era are good. In the Memorial Sloan-Kettering institute
cohort of 12,677 patients who received RP between 1987 and
2005, 15 year OM was 38% and CSM was 12% 48 . CSM ranged from
5% in a low-risk (consisting of 46% of all patients) to 19% in a
high-risk (tPSA > 20 ng/mL or Gleason sum 8-10 or T2c-T3) group.
By multivariate analysis, pre-treatment tPSA and Bx Gleason sum
were pre-operative factors predictive of CSM (Table 4) 48 . Those
with cT3 were at increased risk by univariate analysis (Table 4). RP
Radical prostatectomy can be an option
for selected patients with (very) high-risk
“localised” (cT3-T4) prostate cancer: the
changing treatment paradigm
When high-risk PCa is defined as clinical stage T3-T4 with ECE
(cT3a) or more importantly SVI (cT3b) (Table 2), previously
referred to as locally advanced PCa, RP was not considered an
appropriate local treatment option in the past. Nowadays, several
studies have shown that prognosis in high-risk PCa after RP is
still relatively good (15-year CSM of 19%)48 and that after 10 years
a substantial proportion of high-risk patients is still free from
additional therapy or metastases (Table 5)49.
Table 5. A substantial proportion of high-risk patients is free from additional
therapy or metastases 10 years after radical prostatectomy (RP)49
Estimate of 10-year freedom from
RT
% of high-risk patients
74-86%
specimen primary and secondary Gleason grade 4-5 (Figure 5) and
ADT
41-82%
SVI were post-operative factors predictive of CSM by multivariate
RT or ADT
35-76%
analysis (Table 4)34 . Those with lymph node invasion (LNI) were at
Metastatic disease
72-91%
CSM
89-97%
increased risk by univariate analysis (Table 4) 34 .
ADT: androgen deprivation therapy; CSM: (prostate) cancer-specific mortality; RT: radiotherapy
Table 4. Multivariate analysis shows that pre-treatment total prostate-specific
antigen (tPSA) > 20 ng/mL and biopsy (Bx) Gleason sum 8-10 are important
pre-operative48 and radical prostatectomy (RP) Gleason sum 8-10 and seminal
vesicle invasion (SVI) are important post-operative34 variables predicting 15-year
(prostate) cancer-specific mortality (CSM) following RP
It is also more and more recognized that high-risk PCa represents
a very heterogeneous patient population in terms of prognosis 49.
Further sub-stratification may be required for better predicting
prognosis in individual patients. Briganti, Joniau and co-workers
Mean % 15-year CSM
showed that of 1,366 high-risk (cT3-T4 or Bx Gleason sum 8-10
Pre-treatment tPSA < 4 ng/mL
4
or tPSA ≥ 20 ng/mL) patients, 37% had organ-confined disease at
Pre-treatment tPSA 4-10 ng/mL
9
pathology (i.e. pT2-pT3a, N0, M0) and that these patients had more
Pre-treatment tPSA 10.1-20 ng/mL
11
favourable outcomes in terms of 10-year BCR-free survival and
Pre-treatment tPSA 20.1-50 ng/mL
22
CSS (98% vs. 88%, P < 0.001) than those with non-organ-confined
cT1c
6
disease50. Best disease-free outcomes were noticed in patients with
cT2a
7
cT2b
14
only 1 high-risk factor, and worst but still acceptable outcomes
cT2c
12
cT3
38
Bx Gleason sum 2-6
6
Bx Gleason sum 7
17
Bx Gleason sum 8-10
34
RP Gleason sum ≤ 6
0.2-1.2
These patients, and in particular those with more than 2 positive
RP Gleason sum 3+4
4.2-6.5
nodes, will benefit from adjuvant androgen deprivation therapy
RP Gleason sum 4+3
6.6-11
(ADT) and/or radiotherapy (RT)54,55. Nomograms have also been
RP Gleason sum 8-10
26-37
developed to better predict pre-treatment which cT3a patients will
Organ-confined
0.8-1.5
have N+ disease, i.e. those with Gleason sum 8-10 and tPSA > 50
ECE
2.9-10
ng/mL. In high-risk patients with unfavourable outcomes (positive
SVI
15-27
surgical margins [PSM], ECE and/or SVI) after RP, adjuvant RT has
LNI
22-30
a positive impact on OS after 10 years 56 .
Variable
when all 3 high-risk factors were present 50,51. These investigators
have developed a nomogram to predict which cT3-T4 patients have
pT2 or pT3a (N0, M0) disease50 or pT3b disease. Even patients with
N+ disease can benefit from RP as indicated by improved 10-year
OS rates of 60% vs. 40% (without RP) in German registries 52,53 .
ECE: extracapsular extension; LNI: lymph node invasion
10
10highlights
highlights
Externally validated biomarkers such as microRNA-221 or
Nowadays a surgeon can choose between open (retropubic [RRP]),
algorithms based on multiple genetic markers may in the future
laparoscopic or robotic-assisted RP (RARP) (Figure 8). A final
further help to predict the risk of clinical progression (e.g. CSS) in
question is therefore which type of RP one should use.
high-risk patients and guide individualized treatment .
57
According to the NCCN 2012 guidelines, RP is an appropriate
therapy for any patient with localised PCa with a life expectancy
> 10 years 4 . The EAU 2012 guidelines are more restrictive
and recommend RP only for men with low- or intermediaterisk localised PCa (cT1a-T2b and Gleason sum ≤ 7 and tPSA
≤ 20 ng/‌mL) with a life expectancy > 10 years 3 . They consider RP
optional in selected patients with low volume, high-risk localised
disease (cT3a or Gleason sum 8-10 or tPSA > 20 ng/mL) and in
the context of multimodality treatment also for highly selected
patients with very high-risk localised disease (cT3b-T4, N0 or
any T, N1)3 .
When deciding upon treatment for localised PCa, the abovementioned oncological outcomes should be balanced against
potential complications associated with RP. As indicated before,
the major complications of RP are ED and UI. According to the
EAU 2012 guidelines, ED occurs in 29-100% of patients, slight
stress UI in 4-50%, severe stress UI in 0-15% and urine leak/
fistula in 0.3-15% 3 . Validated health-related quality of life
(HRQoL) questionnaires such as the Short-Form (SF)-36 and
disease-specific QoL questionnaires such as the University of
California-Los Angeles Prostate Cancer Index can provide insight
in the actual impact of RP and other radical therapies on several
QoL domains when used pre- and post-operatively58 . In a study of
Litwin et al. involving 307 men, RP had a considerable impact on
HRQoL, urinary control and sexual function. More specifically,
although physical and mental QoL quickly returned to the baseline
level, many patients had not returned to baseline after 24 months
Figure 8. Development of radical prostatectomy over time
In terms of oncological outcomes laparoscopic or RARP are
probably comparable to RRP 3,4 . Recent recommendations of
the Pasadena Consensus Panel indicate that PSM are at least
equivalent with RARP than with RRP but that firm conclusions
about BCR and other oncological endpoints are difficult to draw
because the follow-up in existing studies is relatively short and
the overall experience with RARP in locally advanced PCa is still
limited 61. RARP is associated with less blood loss and transfusion
rates 61,62 and shorter hospital stay compared to RRP62 and
may offer advantages in post-operative recovery of UI and ED
(although there are methodological limitations in most studies)61.
Complication rates also seem to be lower with RARP than RRP62 .
Experience/a high-volume surgeon seems to strongly predict
better outcomes3,4,61.
for urinary control (40%) or sexual function (60%)58 . Similar data
have been published by other investigators 59,60 . Nerve-sparing
RP showed better recovery in sexual function and UI than nonnerve sparing RP58,59. However, even with nerve-sparing RP only
57% of the typical 60-year old patient with a PSA ≤ 10 ng/mL had
recovery of sexual function 2 years after the surgery59. Older age
contributed negatively to the development of symptoms 59.
highlights highlights
11
Radiotherapy provides comparable
oncological outcomes as radical
prostatectomy in low-risk patients
There are currently no head-to-head RCTs directly comparing
When interpreting external beam radiotherapy (EBRT) results,
RP trials. When EBRT and RP are compared in low-risk patients
it is important to realize that both dose and technology matter.
(which nowadays concerns 30-40% of all patients), there is no
The radiation dose used should be sufficient as it has been
difference in outcomes between EBRT and RP68,69.
demonstrated that only high doses (≥ 72 gray [Gy], but probably
In high-risk patients, RT probably needs to be combined with
even 76-80 Gy 3,63) provide good results 64,65. RT should therefore
long-term (3 years) ADT to optimize oncological outcomes 3,70-73 .
be 3-dimensional conformal (3D-CRT), and, in particular if the
However, it should be realized that most of these trials were
required dose is ≥ 76-78 Gy 3,4 , intensity-modulated (IMRT) 3 and
performed when still suboptimal radiation doses were provided.
EBRT with RP. When making indirect comparisons, it should be
realized that patients included in EBRT trials were usually older,
suffered from more comorbidity, had a higher tPSA and Gleason
sum and had more often high-risk PCa than those evaluated in
preferably also image-guided (IGRT) 3 . A retrospective analysis
involving 376 patients showed that IGRT (at 86.4 Gy) provides
a significant reduction in grade 2 or higher late urinary toxicity
compared with non-IGRT (10.4% vs. 20.0% of patients, P = 0.02)66 .
In addition, high-risk patients had a significant improvement in
BCR-free survival at 3 years.
A simultaneous integrated boost to the dominant intraprostatic
lesion on MRI74 and Cyberknife® robotic surgery, which delivers
very precise beams of high-energy radiation from many angles
outside the body to the tumour, may be promising concepts for
improvement of EBRT oncological and functional outcomes.
Proton therapy may not be the way to go. However, this needs to
A recent randomized controlled trial (RCT) in 414 patients with
T1b-T2, pN0, M0 PCa (1986-1997) has demonstrated that EBRT
(64-68 Gy) performed better than watchful waiting with regard
to 15-year clinical recurrence-free and distant recurrence-free
survival (Table 6)67.
be confirmed in the future by positive long-term follow-up data.
Whereas RP negatively affects urinary control and sexual function,
EBRT negatively affects bowel function and induces rectitis,
eventually bleeding and potentially faecal incontinence 58-60 .
Several nomograms have been developed for predicting the risk
Table 6. External beam radiotherapy (EBRT) is superior to watchful waiting (WW)
in terms of 15-year recurrence-free survival67
of acute and late rectal problems such as bleeding and faecal
incontinence 75,76 . Faecal incontinence is amongst others related
to the dose provided 76 . It seems that genetic factors are also
Oncological outcome
HR (95% CI) for EBRT
(N=207)
HR (95% CI) for WW
(N=207)
P-value
20-yr OS
0.35 (0.25-0.48)
0.31 (0.22-0.42)
0.26
15-yr CSS
0.79 (0.71-0.89)
0.72 (0.63-0.83)
0.31
15-yr distant
recurrence-free survival
0.81 (0.74-0.90)
0.66 (0.57-0.77)
0.022
15-yr clinical*
recurrence-free survival
0.67 (0.58-0.78)
0.40 (0.31-0.51)
<0.001
involved77.
CI: confidence interval; CSS: (prostate) cancer-specific survival; HR: hazard ratio; OS: overall survival; yr: year
* biochemical or local failure or prostate cancer death
12
12highlights
highlights
Brachytherapy is comparable to radical
prostatectomy in terms of 5-year
biochemical recurrence-free survival and can
be an option in low-risk patients
Androgen-deprivation therapy alone is not
indicated for high-risk, non-metastatic
prostate cancer; it can however be used as
adjuvant therapy to local radical therapy
Radiation dose also matters when using brachytherapy (BT): a
In patients with high-risk, non-metastatic (locally advanced)
dose ≥ 130 Gy should be delivered to 90% of the prostate (D90)78
disease, the OS and CSS benefits with ADT alone vs. watchful
and 4-dimensional BT provides a better dose than the Seattle
waiting are only modest 84,85 . Therefore, there is no indication
technique.
for ADT alone in these patients, unless the patients are unfit for
BCR-free survival is 92% in low-risk and 81% in high-risk
patients. The Prostate Cancer Results Study Group evaluated in
radical therapy 3 . In these patients, immediate ADT alone is only
recommended when tPSA > 50 ng/mL or PSA DT is < 12 months 86 .
2012 papers (published between 2000-2010) on radical therapy,
In contrast, immediate and sustained adjuvant ADT in patients
which complied with the following criteria: minimum/median
receiving RT improves OS and CSS 84,85. There is only 1 RCT which
follow-up of 5 years, stratification by low-, intermediate- and
assessed adjuvant ADT following RT in N+ patients; this showed
high-risk groups and minimally 100 patients in each risk group
improved OS 54,55.
(50 for the high-risk group) with BCR-free survival as endpoint .
79
They showed that BT alone may be a good option for low-risk
patients. In high-risk patients, combination therapy of EBRT and
BT, with or without ADT, was superior to BT, RP or EBRT alone.
In a prospective study involving 200 patients, BT appeared to be
comparable to RP in terms of 5 year BCR-free survival: 91.7% vs.
Neoadjuvant standard ADT (i.e. a luteinizing hormone-releasing
hormone [LHRH] agonist or antiandrogen [AA]) before RP has not
been shown to improve OS and CSS 87. However, this may change
upon use of more extensive/aggressive ADT, i.e. a combination of
a LHRH agonist with e.g. dutasteride88 , abiraterone89 or degarelix.
91.0% 80. BT was associated with a higher and longer lasting rate of
urinary irritative disorders and better erectile function than RP.
BT may be in particular useful for (very) low-risk 3 patients with
smaller prostates (size < 60-75 g), a low level of lower urinary
tract symptoms (LUTS; total International Prostate Symptom
Score ≤ 123) who did not recently have a transurethral resection of
the prostate (TURP)3 and have no colitis ulcerosa4 . In combination
with EBRT and/or ADT it may be used in intermediate- to highrisk patients 4 . EBRT in combination with a high-dose rate (HDR)
BT boost may provide best biochemical control and OS when RT
is used 81.
The major complication of BT is LUTS such as weak urinary
stream, straining, urgency, frequency and discomfort with passing
urine due to tissue swelling; urinary retention may also occur in
some patients 3 . The risk of ED and UI are lower with BT than with
RP58-60,82,83 but higher than with EBRT58 . Potency is preserved in
> 80% of patients.
highlights highlights
13
Summary box initial management
of localised prostate cancer with
radical therapy
• RP performs very well with regard to 15-year CSM
ranging from 5% in low-risk to 19% in high-risk
patients
• When deciding on treatment, this oncological outcome
should be weighed against major complications such
as ED and UI. Full recovery within 24 months may not
occur in 40-60% of patients
• RP can be recommended for patients with low- to
intermediate-risk localised PCa (cT1a-T2b and Gleason
sum ≤ 7 and tPSA ≤ 20 ng/mL) with a life expectancy
> 10 years
• Modern EBRT should be given at a sufficient radiation
dose ≥ 72 Gy and, if ≥ 76-78 Gy is required, it should be
intensity-modulated and image-guided
• In low-risk patients, there seems to be no difference in
oncological outcomes between RP and EBRT
• Nomograms can be used to estimate the risk of acute
and late rectal problems such as bleeding and faecal
incontinence following EBRT
• BT is comparable to RP in terms of 5-year BCR-free
survival (around 91%) and can be an appropriate
option in low-risk patients, provided they have a small
Pelvic lymph node dissection should be
extended (removal of ≥ 20 nodes) and be
performed if the risk of lymph node invasion
is ≥ 5%
Computed tomography (CT) and standard MRI have limited
ability (sensitivity around 40%) 91 in detecting LNI because
most metastases in lymph nodes are < 10 mm. Intravenous
injection with ultra small particles of iron oxide (USPIO) using
Ferumoxtran-10 in combination with MRI has a sensitivity of 96%
and specificity of 99% for detecting metastases in lymph nodes
between 5 and 10 mm92; for detecting nodes < 5 mm sensitivity is
41%. Unfortunately, Ferumoxtran is not commercially available
and its alternative Ferumoxytol provides less positive results (AUC
reduced from 0.92 to 0.74). Preliminary results with DWI-MRI are
not good (sensitivity 19%) and the technique is not ready for use
in clinical practice93. Performance of 11C-choline positron emission
tomography (PET)/CT scan for detecting positive lymph nodes pretreatment shows varying results (specificity 90-95%, sensitivity
60-80%) 93 and is not widely available. Therefore, pelvic lymph
node dissection (LND), either open, robotically or laparoscopic, is
still the gold standard for N-staging during RP although there is
still no level 1 evidence for cure 3 .
The questions to ask are in whom to perform LND and to which
extent (limited or extended LND). In recent years, there has been a
prostate, minimal LUTS and have not recently had a
tendency for a reduction in the number of lymph nodes removed 94 .
TURP
• BT can induce LUTS such as weak stream, urgency and
and external iliac artery areas) detects LNI in only around 2-4%
frequency due to swelling of prostatic tissue
• EBRT in combination with a HDR BT boost may provide
best biochemical control and OS when RT is used
• ADT alone is not indicated for patients with localised
However, limited LND (removal of nodes in the obturator fossa
of patients 94 , is associated with a high false-negative rate and
gives away the window for cure. The rate of LNI increases with the
number of removed nodes 95 from 5.6% at removal of 2-10 nodes
to 17.6% at removal of 20-40 nodes (Figure 9) 96 .
disease, also not for those with high-risk PCa (unless
patients are unfit for radical therapy)
• In selected high-risk patients (cT3a or Gleason sum
8-10 or tPSA ≥ 20 ng/mL) RP can be an option and
in highly selected very high-risk patients (cT3b-T4,
N0 or any T N+) RP can be the first treatment in a
multimodality approach including adjuvant RT and/
or adjuvant ADT and lymph node dissection, even in
patients with N+ disease. Adjuvant RT is indicated in
patients with a least 1 unfavourable factor (PSM, ECE
and/or SVI) and a life expectancy > 10 years while
adjuvant ADT is indicated in patients with N+ disease
Figure 9. The lymph node invasion (LNI) rate increases with the number of nodes
removed in 858 patients of whom 88 (10.3%) had LNI96
14
14highlights
highlights
Removal of at least 20 nodes detects lymph node metastases
in 90% of patients 97. Therefore, LND should be extended 3,4 , i.e.
removal of at least 20 nodes97 from at least the obturator fossa and
the external and internal iliac artery and possibly also including
the common iliac artery98 (Figure 10), despite a potential higher
rate of complications (in particular lymphoceles) and a longer
Points
Prostate specific
antigen
0
0
10
5
20
10
95
operating time. It should be noted that the benefit of extended
over limited LND on CSM and OS has not been tested. The impact
of limited vs. extended LND on 5 year progression-free survival
(PFS) is currently investigated in 500 patients with intermediateor high-risk PCa (i.e. tPSA > 10 ng/mL, stage ≥ cT2b and Bx
Gleason sum ≥ 7) by the Deutsche Krebsgesellschaft.
Clinical stage
25
30
50
35
60
40
45
70
80
90
100
80
90
100
50
cT2
cT3
≥4
≤3
Secondary Gleason
grade
≤3
Percentage of
positive cores
0
Probability of LNI
20
40
cT1
Primaruy Gleason
grade
Total points
15
30
≥4
0
10
20
50
0.025
30
40
100
150
0.1
50
60
200
70
250
0.2 0.3 0.4 0.5 0.6 0.7 0.8
300
0.9
350
0.95
Figure 11. Extended lymph node dissection-based nomogram to estimate risk
of N+ disease pre-operatively based on total prostate-specific antigen, clinical
stage, Gleason grades and % of positive cores. Reproduced from Briganti A, et
al.100, with permission from Elsevier Limited
Figure 10. Lymph node dissection should be extended and lymph nodes should be
removed in the following areas: the obturator fossa, the external and internal iliac
artery and possibly also the common iliac artery. Reproduced from Mattei A, et
al.98, with permission from Elsevier Limited
The sentinel lymph node is the hypothetical first lymph node or
group of nodes draining a cancer. In case of established cancerous
dissemination it is postulated that the sentinel lymph node/s is/
are the target organs primarily reached by metastasizing cancer
cells from the tumour. If the sentinel lymph node is negative,
At extended LND, the incidence of LNI is around 10% 96,99,100 but
LND can be stopped. The rationale for sentinel node dissection
this increases from 2% for low-risk, 8% for intermediate-risk
is to retain diagnostic accuracy compared with extended LND
(tPSA 10-20 ng/mL, ≥ cT2b and Bx Gleason sum 7) to 34% for
with a reduction of morbidity and a shorter operating time.
high-risk (tPSA > 20 ng/mL, ≥ cT3 and Bx Gleason sum 8-10)
This technique involves injection of bilobar-filtered sulfur
patients. In this respect, the Gleason sum is probably much more
colloid tagged with 99MTechnetium (at least 200 MBq) to detect
important than tPSA 101. Including the percentage of positive cores
radioactive lymph nodes at pelvic scans which are excised with a
further increases the likelihood of detecting LNI 100. LND should
gamma probe during surgery. SPECT-CT/MRI imaging allows for
be performed if the risk of LNI as assessed in updated/extended
perfect anatomical targeting during surgery. Preliminary studies
LND-based nomograms (Figure 11) is ≥ 5% 3,100, i.e. in patients at
with sentinel node dissection were positive (false-negative rate
intermediate- or high-risk .
6%)102,103 . A recent study performed by Joniau et al. compared
3,4
sentinel node dissection with (super) extended LND. Out of 74
patients at high risk of LNI (57% with pT3 and 43% with Gleason
sum 8-10 cancer), 34 patients (46%) had N+ disease. Sentinel node
dissection correctly staged N+ in 26 out of 33 patients (79%).
However, (super) extended LND outperformed sentinel node
dissection: 32 (33) out of 34 patients were correctly staged.
highlights highlights
15
Summary box lymph node dissection
• LND should be extended and remove at least 20 lymph
nodes in at least the obturator fossa and the external
and internal iliac artery areas and possibly also in the
How to manage patients with unfavourable
pathological outcomes after radical
prostatectomy or recurrence after local
radical therapy?
common iliac artery area (super extended LND)
• LND should not be performed in men with < 5%
Patients who have ECE, PSM, SVI, pN+, pT3b and/or pGleason sum
risk of LNI, i.e. not in men with low-risk PCa
8-10 after a RP are at high risk of “systemic” recurrence and related
(tPSA < 10 ng/‌mL, cT1c-T2, Gleason sum ≤ 7)
death 34 . The question is how to further manage these patients.
• (Super) Extended LND still outperforms sentinel node
dissection in terms of positive LN detection
• The benefit of extended LND vs. limited on CSM and
OS has not been demonstrated
Should one start with immediate adjuvant RT or ADT or should
one wait with salvage therapy until actual BCR? It should also be
taken into account that although 30-50% of patients have BCR/
PSA relapse and 15-25% have local recurrence after RP104 , OS (9290% at 5 and 10 years, respectively) and metastasis-free survival
(92-85% at 5 and 10 years, respectively) are still good. Even after
BCR, OS after 10 years is around 90% and metastasis-free survival
82-87%105.
There is no evidence from RCTs in support of adjuvant vs. salvage
RT. Data from 3 clinical trials with adjuvant RT (SWOG 8794,
N=425106 , EORTC 22911107, N=1,005 and ARO 96-02, N=388108)
show that the metastasis-free survival and OS benefit is largely
due to fewer deaths from competing causes and that the benefit
is mainly noticed in high-risk patients (pT3b or higher and/or in
those with PSM). 10-year follow-up of the EORTC 22911 study
in patients with PSM or pT3 after RP has shown that adjuvant
RT improves BCR-free survival and local control but does not
significantly impact distant metastases or OS109 . In addition,
it has been demonstrated that early salvage RT improves CSM
and that 50% of patients are after 6 years still progression-free
when RT is given at low tPSA level (< 0.5 ng/mL: Figure 12)104,110.
Therefore, it can be concluded that in patients with unfavourable
pathological outcomes after RP, the window of opportunity to cure
is not lost when waiting for a PSA rise. Taking into account that
RT can induce rectal complications, strictures and UI, early (PSA
≥ 0.03 ng/mL or < 0.5 ng/mL) salvage RT at a dose of 64-66 Gy
seems to be the best option for most patients 3,4 . Adjuvant RT is
justified for high-risk patients (Gleason sum 8-10, SVI and/or N+)
or those with PSM.
16
16highlights
highlights
1.0
0.8
0.8
Cancer specifics survival
Proportion free of progression
1.0
0.6
PSA < 0.5 ng/mL
0.4
PSA 0.5-1.00 ng/mL
0.2
PSA 1.01-1.50 ng/mL
PSA > 1.50 ng/mL
2 pN+ (n = 27)
0.6
1 pN+ (n = 47)
0.4
≥3 pN+ (n = 48)
0.2
Log rank <0.001
0
12
24
36
48
60
72
84
96
108 120
0.0
Time from salvage radiotherapy end (months)
0
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20
Time (years)
Figure 12. With early (prostate-specific antigen [PSA] < 0.5 ng/mL) salvage
radiotherapy, around 50% of patients with recurrence after radical prostatectomy
are still progression-free after 6 years. Reproduced from Stephenson AJ, et al.104,
with permission from the American Society of Clinical Oncology
Figure 13. Outcome in patients with few positive lymph nodes after radical
prostatectomy is good. Reproduced from Schumacher MC, et al.112, with
permission from Elsevier Limited
For ADT, the magnitude of the benefit of adjuvant therapy is not
Since it has been shown to increase CSS and OS in locally advanced
impressive for OS, only for metastasis-free survival. Whereas one
disease historically treated with ADT only, the question of local
non-randomized, retrospective study with a median follow-up
and distant RT is now addressed in patients with low burden
of 11.9 years showed a significant improvement in OS, CSS and
metastatic disease, aka oligo-metastastic disease. In a small study
PFS in 98 N+ patients receiving adjuvant ADT54 , a retrospective
involving 24 patients with 49 lesions (22 in the lymph nodes and
analysis of the SEER Medicare database in 731 N+ patients of
27 in bone) who received high-dose RT, ADT was initiated at the
whom 209 received ADT within 120 days after surgery did not
diagnosis of polymetastases (> 3), a tPSA > 50 ng/mL, a PSA DT
. Moreover, CSS in patients with extended LND
< 4 months and/or when symptoms developed. After 2 years,
after RP is quite good in patients with limited node disease
54% of patients were still ADT-free. Patients with asymptomatic
(< 3 positive nodes: Figure 13)
polymetastases should still receive ADT. This concept will be
confirm this
111
112
. Therefore and because ADT can
be associated with side effects such as impaired physical activity,
further investigated in a clinical trial.
sexual dysfunction, sarcopenic obesity, metabolic syndrome and
Nodal recurrence detection after both RP and RT may be improved
osteoporosis, adjuvant ADT should be restricted to patients with
by new imaging techniques, including 11C-choline PET/CT scan.
massive (> 2) positive nodes. Adjuvant ADT may also be considered
11
C-choline PET/CT scan has good sensitivity and specificity
in patients with pT3b and Gleason sum 8-10 disease. Salvage ADT
for detecting positive nodes although it can still miss micro
is questionable when the PSA DT is very low.
metastases (< 5 mm) and is associated with high costs. A positive
PET/CT scan is highly PSA dependent (Figure 14); a cut-off of 1.01.5 ng/mL has shown good discriminative power 113 . However,
around 20-25% of patients with a PSA < 1.0-1.5 ng/mL still have a
positive PET/CT scan. In these patients, a low PSA DT (< 6 months)
is a good predictor of a positive PET/CT scan (Figure 14)114,115.
highlights highlights
17
that salvage RP offers the best oncological outcomes (Table 7)118 , in
particular in patients with a pre-operative tPSA < 4.0 ng/mL119,120
and in Gleason sum ≤ 7120 , but at the expense of a high risk of UI
and bladder neck contracture (BNC)121. The rate of complications
is independent of the type of RP, being open or minimally invasive
surgery (MIS: laparoscopic or robotic), with the exception of a lower
BNC rate with MIS (Table 7).
Figure 14. Still 19% of 358 patients with a total PSA (tPSA) < 1 ng/mL after radical
prostatectomy have a positive PET/CT scan (left)113. In 170 patients with a median
tPSA of 1.25 ng/mL, a PSA doubling time (DT) < 6 months was predictive of a
positive PET/CT scan (right)114
With new imaging techniques allowing earlier identification of
isolated LN recurrence, it is now tempting to offer the patient the
chance of a second-line surgical extirpation of visible tumours.
However, data on salvage LND are rare and conflicting
. In a
after salvage LND116 . However, only 29 patients had not received
ADT; in these patients BCR-free survival after 5 years was only
10% (Figure 15). In another small study in 15 patients, only
1 patient reached the PSA nadir of < 0.1 ng/mL 117. In addition,
cancer control should be balanced against LND morbidity (in
particular lymphorrhea and lymphocele) and should still be
considered as experimental 3 .
10-year BCR-free survival
37%
(95% CI: 31-43%)
10-year metastasis-free survival
77%
(95% CI: 71-82%)
10-year CSS
83%
(95% CI: 76-88%)
Open121
MIS: Laparoscopic/
Robotic121
Rectal injury
0-9%
0-9%
BNC
11-41%
0-17%
Clavien 3-5
0-30%
0-17%
Urinary continence
21-83%
0-80%
BNC: bladder neck contracture; BCR: biochemical recurrence, i.e. total prostate-specific antigen ≥ 0.1 ng/mL;
CI: confidence interval; CSS: (prostate) cancer-specific survival; MIS: minimally invasive surgery
In patients with recurrence after local RT, salvage BT in 37 patients
seemed to have, when indirectly compared, the same oncological
outcomes as RP (10-year BCR-free survival 53.5% and 10-year CSS
Time after surgery
96%)122 . The benefits were higher in those with lower tPSA levels
1 year
3 years
5 years
55.2
(35.6-71)
27.5
(13-44.3)
10.3
(2.6-24.3)
n. at risk
18
8
3
For salvage cryotherapy, the long-term oncological outcomes are
n. of events
11
18
22
limited and the definition of BCR is unclear123 . In a retrospective
% biochemical recurrence-free
survival (95% C.I.)
1.0
RP
(N=404)118
116,117
study in 72 patients, 56.9% reached a PSA nadir of < 0.2 ng/mL
0.9
Table 7. 10-year survival of salvage radical prostatectomy (RP) for recurrence
following local radiotherapy is good and complication rates (after the year 2000)
are not very different for the different types of RP
0.8
(< 6 ng/mL). However, further studies are required to confirm this.
chart review, outcomes with salvage cryotherapy (follow-up
0.7
5.5 years) were also less good than with RP (follow-up 7.8 years):
0.6
0.5
5-year BCR-free survival 21% vs. 61% (P < 0.001) and 5-year OS
0.4
85% vs. 95% (P < 0.001); 5-year CSS was similar (96% vs. 98%)124 .
0.3
In addition, although the complications rate is due to technical
0.2
improvements currently lower than with RP, it is still substantial:
0.1
incontinence in 6-40% of patients, obstruction in 3-21%, perineal
0.0
0
12
24
36
48
60
72
pain in 8-40% and fistula in 0-3%123 .
Time (months)
Following BT, 10-year OS and CSS are very good: respectively 68%
Figure 15. In patients not receiving androgen deprivation therapy (ADT), the
biochemical recurrence-free survival 5 years after salvage lymph node dissection
is only 10%. Reproduced from Rigatti P, et al.116, with permission from Elsevier
Limited
For recurrence after local RT, salvage RP, BT, cryotherapy or High
Intensity Focused Ultrasound (HIFU) may be considered in addition
to ADT. In the absence of proper randomized trials, it is impossible
and 95% in low-risk and 49% and 69% in high-risk patients125 .
Recurrence may be due to the fact that the dose delivered is too
low due to seed migration 126 . Due to their low sensitivity, PSA
and Bx should not be used to assess response to or recurrence
after BT127. Imaging techniques are promising 128,129 but not yet
established. The clinical relevance of salvage therapy after BT is
uncertain.
to compare these approaches. Based on very limited trials, it seems
18
18highlights
highlights
Summary box adjuvant or salvage
therapy after local radical therapy
• Men at high risk of systemic recurrence after RP or
with BCR/PSA relapse still have a good 10-year OS
(around 90%) and metastasis-free survival (around
85%). This outcome as well as potential induced
morbidity should be taken into account when initiating
In PCa, metastases are predominantly found in the bones (63%)
treatment after RP
and lymph nodes (36%) and only rarely in visceral organs such as
◦◦ Adjuvant RT improves biochemical and clinical
recurrence. The benefit on metastasis-free survival
and OS has not been demonstrated in all trials.
Based on retrospective data, it appears that early
salvage RT may be an alternative if administered
at low PSA levels (< 0.5 ng/mL).
◦◦ Taken into account the considerable side effects
of ADT, adjuvant ADT should only be considered
in patients with > 2 positive lymph nodes after
RP, whereas salvage ADT should not be given to
patients with a very short PSA DT
•
Whole-body and axial skeleton MRI has
improved sensitivity and specificity over
the multi-step approach of bone scan with
targeted imaging (X-ray/CT/MRI) in the
detection of metastases
C-Choline PET/CT scan has a good sensitivity/
11
specificity for detecting positive lymph nodes but can
still miss small lesions (< 5 mm). The results are also
PSA dependent; below a cut-off of 1.0-1.5 ng/mL, still
20-25% have positive nodes. In these patients, a PSA
DT < 3 months is predictive of a positive choline PET/
CT scan. The benefit of 11C-choline PET/CT on CSS and
OS has not been demonstrated and it should therefore
still be considered experimental
• The role of salvage LND should also still be considered
experimental
• Recurrence after local RT is from an oncological point
of view still best treated with salvage RP although the
the liver and lungs (6%).
As indicated before extended LND is still the gold standard for
detecting N+ disease in PCa. The gold standard for detecting
bone metastases (except for asymptomatic patients with tPSA
< 20 ng/‌m L and ≤ Gleason 3+4) is bone scintigraphy/scan 3 .
However, it should be realized that it is associated with false
positives as other pathologies to the bones (degenerative disease,
inflammation, trauma, etc.) may also produce “hot spots”.
Therefore, a positive or equivocal bone scan is followed by targeted
imaging by means of a targeted X-ray (TXR), CT scan and/or MRI.
As the skeleton will be later (i.e. months) positive than the bone
marrow, metastases may be picked up earlier with MRI than with
a bone scan. Not surprisingly perhaps that a study in 100 patients
at high-risk for developing metastases comparing the standard
for detecting bone metastases (i.e. bone scan followed by targeted
imaging) with whole-body (WB)-MRI showed better sensitivity
with MRI (Table 8)130. Axial skeleton (AS)-MRI, which is limited
to the axial skeleton (i.e. spine, pelvis, proximal femurs, ribs and
skull), i.e. the areas where PCa metastases can be found, also
outperformed standard of care in 66 patients (Table 8)131.
Table 8. Whole-body MRI (WB-MRI) and axial skeleton MRI (AS-MRI) show
increased sensitivity compared with standard care in detecting bone metastases
in high-risk PCa patients
rate of incontinence and BNC is high. Salvage BT needs
further studies
Standard care (N = 100)*130
WB-MRI (N = 100)
Sensitivity
Specificity
86%
98%
98-100%
98-100%
Standard care (N = 66)*131
83%
100%
AS-MRI (N = 66)131
100%
88%
130
* bone scan followed by a targeted X-ray (and MRI on request if results remained equivocal)
highlights highlights
19
Therefore, from a time, cost, injections, radiation, convenience and
diagnostic accuracy point of view, a single-step AS- or WB-MRI
may be a preferred over the currently recommend sequential
multi-step approach, in particular because it not only visualizes
bone but also lymph node metastases. AS-MRI is also able to
measure and monitor reduction or progression of bone metastases
after treatment in a considerable proportion of patients132 .
The future challenge in managing metastatic
castration-resistant prostate cancer will be
to assess how to best sequence, combine
and/or individualize all new treatment
options (depending on availability/price)
An 11C-choline PET/CT scan for detecting bone metastases is
promising but overall performance remains currently unclear.
ADT with a LHRH agonist (and/or an AA) or antagonist is standard
DW-MRI has been shown to be effective but the technique must
treatment for men with (symptomatic) metastatic PCa 3 . However,
be further optimized.
eventually (after 9-16 months in symptomatic patients 3) these
As indicated before, visceral metastases in e.g. the liver and lungs
are rare at initial diagnosis. Chest XR and a chest/abdominal
CT scan are standard diagnostic techniques used for detecting
visceral metastases.
When post-treatment biochemical recurrence (PSA > 0.2 ng/mL
for 2 consecutive PSA measurements post-RP or PSA 2 ng/mL
above nadir with short PSA DT post-RT) or distant metastases
(early PSA rise, high PSA velocity [> 0.75 ng/mL/yr] and short
PSA DT [< 6 months]) are suspected, the same scheme as for
metastases can be used.
patients will develop metastatic castration-resistant PCa (mCRPC).
Until 2004, mCRPC was uniformly lethal. The field of mCRPC
revolutionized in 2004 when two agents (docetaxel and zoledronic
acid) were introduced.
Zoledronic acid, a third generation biphosphonate, has been
shown to delay the development of skeletal complications of bone
metastases, including fractures, spinal cord compression and
the need for surgical or radiotherapeutic intervention 133 . These
complications are now termed skeletal related events (SREs).
Docetaxel is a taxane that has been shown in two landmarks trials
to improve PSA response, OS, pain control and QoL in patients
with mCRPC134,135.
Summary box detection of
metastases
Since 2010, results of phase III trials with several new agents in
mCRPC have shown positive results (Table 9). These drugs are now
progressively incorporated in current practice.
• Extended LND is still the gold standard for detecting
metastases in the lymph nodes
• The multi-step approach of a bone scan followed by a
targeted X-ray/CT/MRI in those with a positive bone
scan is still the standard for detecting bone metastases.
Table 9. Impact of several new treatments for metastatic castration-resistant
prostate cancer on overall survival (OS)
Trial
N
Novel agent
Comparator
Adjuvant
HR
Median OS
(months)
However, WB-MRI or AS-MRI as a single-step may be
TAX 327
1,006
docetaxel
mitoxantrone
prednisone
0.76
18.9 vs. 16.6
preferred because it is able to measure the extent of the
SWOG 9916
674
docetaxel
mitoxantrone
estramustine/
prednisone
0.80
17.5 vs. 15.6
IMPACT
512
sipuleucel-T
placebo
N/A
0.78
25.8 vs. 21.7
TROPIC
755
cabazitaxel
mitoxantrone
prednisone
0.70
15.1 vs. 12.7
COU-AA-301
1,195
abiraterone
placebo
prednisone
0.65
14.8 vs. 10.9
ALSYMPCA
921
radium-223
placebo
best supportive
care
0.70
14.9 vs. 11.3
AFFIRM
1,199
enzalutamide
placebo
allowed:
prednisone
0.63
18.4 vs. 13.6
metastases and can as such also monitor progression or
reduction following treatment
• A chest X-ray and a chest/abdominal CT scan are
standard diagnostic techniques used for detecting
visceral metastases
HR: hazard ratio; N/A: not applicable
Denosumab (subcutaneous injections of 120 mg every 4 weeks)
is a fully human monoclonal antibody approved by the FDA and
European Medicines Agency (EMA) in 2010 and 2011, respectively,
for the prevention of SREs in patients with bone metastases. One
phase III trial in 1,901 patients with mCRPC and bone metastases
comparing zoledronic acid with denosumab showed that although
there was no difference in OS and time to progression, denosumab
delayed time to first SRE (20.7 months) statistically significantly
more than zoledronic acid (17.1 months) 136 . Whereas twice as
many patients on denosumab had hypocalcaemia (13% vs. 6% of
20
20highlights
highlights
patients) and osteonecrosis of the jaw (2% vs. 1%), patients on
Alpharadin or Radium-223 (6 intravenous injections of 50 kBq/kg,
zoledronic acid required more dose adjustments for renal function
every 4 weeks) is the first bone-targeting radiopharmaceutical
(22% vs. 0%).
to show survival improvement in 809 mCRPC patients with
Sipuleucel-T (intravenous infusions every 2 weeks for a total of 3
bone metastases in a planned interim analysis of the phase III
cycles) is a vaccine-type immunotherapy designed to stimulate
an immune response targeting PCa cells. It has been approved
by the FDA in 2010 for asymptomatic or minimally symptomatic
mCRPC patients who do not have hepatic metastases based on the
phase III trial (IMPACT) in 512 patients137. This trial showed that
at 36 months, still 32.1% on sipuleucel-T were alive as compared
to 23.0% on placebo; OS was 25.8 vs. 21.7 months. EMA approval
is expected in 2013.
Cabazitaxel is a novel taxane-class cytotoxic agent. It has been
approved by the FDA in 2010 and the EMA in 2011 as secondline therapy (25 mg/m2 intravenously every 3 weeks in addition
trial ALSYMPCA compared with placebo 142 . It showed that
radium-223 significantly improved OS in patients with CRPC
with bone metastases compared to placebo (14.9 vs. 11.3 months,
P = 0.00007). It is of note that radium-223 also reduced the
occurrence of SREs and significantly delayed the time to first SRE
(15.6 mo vs. 9.8 mo, P = 0.00037). Radium-223 is associated with a
low incidence of bone marrow suppression compared with placebo
(grade 3 to 4 neutropenia 2.2% vs. 0.7% and thrombocytopenia
6.3% vs. 2%); there was no significant difference in gastrointestinal
disorders compared with placebo. Radium-223 is not yet approved
by the FDA or EMA.
to daily prednisone 10 mg) for patients progressing during or
after first-line docetaxel chemotherapy based on the results of
the phase III TROPIC study in 755 patients138 . It prolonged PFS
and OS statistically significantly more than mitoxantrone. After
24 months, 28% of patients on cabazitaxel as compared to 17%
of patients on mitoxantrone were still alive, i.e. a 30% reduction
in the risk of death, at the expense of more febrile neutropenia
(grade 3-4: 8% vs. 1%) and diarrhoea (grade 3-4: 6% vs. < 1%).
The FIRSTANA trial is currently evaluating whether in chemonaïve mCRPC patients cabazitaxel can be used as first-line
chemotherapy instead of docetaxel.
Summary box metastatic castrationresistant prostate cancer
• ADT with a LHRH agonist is standard treatment for
patients with metastatic PCa
• In 2004, the cyotoxic agent docetaxel was the first
treatment to demonstrate improved OS in patients
with symptomatic mCRPC
• Denosumab, a human monoclonal antibody, is superior
to zoledronic acid in delaying the time to first SRE in
Abiraterone is a selective inhibitor of CYP17, a key enzyme involved
in androgen and oestrogen synthesis. It has been approved in 2011
patients with mCRPC and bone metastases
• Sipuleucel-T, an immunotherapy, is indicated for
by both the FDA and EMA as second line therapy (1,000 mg orally
asymptomatic or minimally symptomatic mCRPC
in addition to daily prednisone 10 mg) for patients progressing
• Patients with mCRPC progression during or following
during or after first-line docetaxel chemotherapy based on the
docetaxel are candidates for treatment with
results of the phase III COU-AA-301 study in 1,195 patients
cabazitaxel, abiraterone and enzalutamide
139
. It
prolonged PFS and OS statistically significantly more than placebo
(14.8 vs. 10.9 months, P < 0.0001). Adverse events associated with
elevated mineralocorticoid levels due to CYP17 blockade (i.e.
fluid retention, oedema, hypertension, hypokalaemia) as well
as cardiac disorders and liver function abnormalities were more
frequent in the abiraterone group compared to the placebo group.
The COU-AA-302 trial investigated abiraterone in 1,088 chemonaïve mCRPC patients. An interim analysis revealed a significant
improvement in radiographic PFS (0.43 [0.35-0.52]; P < 0.0001)
and a strong trend for OS improvement (0.75 [0.61-0.93];
P = 0.0097]140.
Enzalutamide (MDV3100: 160 mg daily) is a new generation AA.
It has been shown in 1,199 patients with progressing mCRPC
following docetaxel in the AFFIRM trial to improve OS compared
with placebo (18.4 vs. 13.6 months, P < 0.0001), reducing the risk
of death by 37%141. The PREVAIL study is currently investigating
enzalutamide in chemo-naïve mCRPC patients. It was very
recently (end of August 2012) approved by the FDA.
highlights highlights
21
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22
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24
24highlights
highlights
Abstracts of the Global Congress on
Prostate Cancer, 1st edition
Brussels, Belgium, 28-30 June 2012
Table of contents
Abstracts accepted for oral presentation main session . . . . . . . . . . . . . . . . . 28-29
Abstracts accepted for oral presentation poster session. . . . . . . . . . . . . . . . 30-44
Abstracts accepted for poster presentation . . . . . . . . . . . . . . . . . . . . . . . . . . 44-66
Authorlist ���������������������������������������������������������������������������������������������������������������� 67
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abstracts ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������� 25
Abstracts accepted for oral
presentation main session
The 4 winning abstracts are presented on Saturday at 12.00
during the main session in Auditorium 1. For detailed
programme see live screens or http://live.prosca.org
1
Primary, secondary, and quality-of-life endpoint results from
the Phase 3 AFFIRM study of MDV3100, an androgen receptor
signaling inhibitor
Sternberg CN1, Scher HI2, Fizazi K3, Saad F4, Taplin ME5, Miller K6, Mulders PFA7, Chi
KN8, Armstrong AJ9, Hirmand M10, Selby S11, de Bono JS12, for the AFFIRM Investigators.
1
Department of Medical Oncology, San Camillo Forlanini Hospital, Rome, Italy; 2Sidney
Kimmel Center for Urologic and Prostate Cancers, Memorial Sloan-Kettering Cancer
Center, New York, NY, United States; 3Department of Cancer Medicine, University of
Paris Sud, Villejuif, France; 4University of Montreal Hospital Center, University of
Montreal, Montreal, QC, Canada; 5Genitourinary Cancer Treatment Center, DanaFarber Cancer Institute, Boston, MA, United States; 6Department of Urology, Charité
- Universitätsmedizin Berlin, Berlin, Germany; 7Department of Urology, Radboud
University Nijmegen Medical Centre, Nijmegen, Netherlands; 8Department of Medical
Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada;
9
Department of Medicine, Duke University, Durham, NC, United States; 10Clinical
Development, Medivation, Inc., San Francisco, CA, United States; 11Department of
Biometrics, Medivation, Inc., San Francisco, CA, United States; 12Drug Development
Unit, Institute of Cancer Research, London, United Kingdom
Background: MDV3100, a novel androgen receptor (AR)
signaling inhibitor (ARSI), inhibits: 1) binding of androgens to
AR, 2) AR nuclear translocation, and 3) association of AR with
DNA. MDV3100 was active in a phase 1-2 trial enrolling pre- and
post-docetaxel castration-resistant prostate cancer (CRPC)
patients. The AFFIRM trial evaluated whether MDV3100 could
provide benefit to men with post-docetaxel metastatic CRPC
(mCRPC).
Methods: In this double-blind, multinational phase 3 study,
mCRPC patients who had received 1-2 lines of therapy, including
prior docetaxel-based chemotherapy were randomized 2:1 to
MDV3100 160 mg/day or placebo. Treatment with
corticosteroids was not required but allowed. Patient
randomization was stratified by baseline ECOG and mean brief
pain inventory score. The primary endpoint was overall survival
(OS). Other efficacy endpoints included radiographic
progression-free survival (rPFS), time to PSA progression
(TTPP), soft tissue objective response (PR+CR), PSA response
(>50% decrease), and quality-of-life (QoL) response (>10 point
improvement in FACT-P global score).
Results: 800 patients were randomized to MDV3100 and 399 to
placebo with respective median treatment durations of 8.3 and
3.0 months. The treatment groups were well-balanced with a
significant proportion of patients having >20 bone lesions
(37.8% MDV3100 vs 37.8% placebo) or visceral liver/lung lesions
(24.5% MDV3100 vs 20.6% placebo). Efficacy results are
presented (Table).
MDV3100
Placebo
HR (95% P-value
CI)
<0.0001
25.1%+3.8% 2.9%+1.0%
0.631
(0.529,
0.752)
0.404
(0.350,
0.466)
0.248
(0.204,
0.303)
-
54.0%
1.5%
-
<0.0001
43.3%
17.8%
-
<0.0001
OS,
median
18.4 months 13.6 months
rPFS,
median
8.3 months
2.9 months
TTPP,
median
8.3 months
3.0 months
PR+CR
PSA
response
QoL
response
<0.0001
<0.0001
<0.0001
The most common MDV3100 adverse events with incidences
higher than placebo were fatigue (34% vs 29%), diarrhea (21%
vs 18%), and hot flush (20% vs 10%). Grade >3 events of interest
were cardiac disorders (0.9% MDV3100 vs 2% placebo), fatigue
(6% MDV3100 vs 7% placebo), seizure (0.6% MDV3100 vs
0% placebo), and LFT abnormalities (0.4% MDV3100 vs 0.8%
placebo).
Conclusions: MDV3100, a novel ARSI, is generally well-tolerated
and significantly prolongs OS, slows disease progression, and
improves QoL in men with mCRPC post-docetaxel.
2
Radium-223 chloride (Ra-223), a first-in-class alphaemitter: product profile and clinical experience in patients
with castration-resistant prostate cancer (CRPC) and bone
metastases
Nilsson S1, Parker C2, Biggin C3, Staudacher K3, Aksnes AK3, Zou J4, Bruland ØS5.
1
Radiumhemmet, Karolinska University Hospital, Stockholm, Sweden; 2Radiotherapy,
The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom; 3Algeta ASA,
Oslo, Norway; 4Bayer HealthCare Pharmaceuticals, Montville, NJ, United States;
5
Oncology, Norwegian Radium Hospital, University of Oslo, Oslo, Norway
Introduction: Ra-223 is a first-in-class alpha-emitter with a
potent, targeted, antitumor effect on bone metastases and a
favorable safety profile. High-energy alpha-radiation induces
double-strand DNA breaks, causing highly localized cytotoxicity
in metastatic cancer cells, sparing other healthy tissue and bone
marrow. Product profile and clinical experience from phase I, II,
and III studies are described.
Methods: Radiation properties of Ra-223 allow for its safe use.
Two open-label phase I trials (n=37) and 3 double-blind phase II
trials (n=255) assessed Ra-223 dosimetry, safety, and efficacy.
Single intravenous doses ranged from 5 to 250 kBq/kg b.w.;
repeated dosage regimens varied. Clinical efficacy and safety were
assessed in a multinational, randomized, double-blind phase III
trial (ALSYMPCA) in 921 CRPC patients with bone metastases
receiving 6 injections of Ra-223 50 kBq/kg b.w. every 4 weeks
plus best standard of care (BSC).
Results: The 11.4-day physical half-life of Ra-223 facilitated
its preparation, distribution, and administration with minimal
shielding requirements. The ultra-short penetration of alphaparticles permits easy handling of Ra-223 and repeated
injections. Treatment was delivered on an outpatient basis with
26 ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������ abstracts
minimal radiation protection restrictions after treatment. As
there is a small component of gamma-radiation with Ra-223
decay, standard contamination monitoring equipment can be
used.
In the phase II placebo-controlled study in 64 patients receiving
BSC plus either Ra-223 or placebo, median survival increased
by 4.5 months (P=0.017), serum bone alkaline phosphatase
decreased significantly, and time to prostate-specific antigen
progression was significantly prolonged with Ra-223. These
findings are consistent with the clinical benefit reported in the
interim analysis of 809 patients in the ALSYMPCA trial (median
overall survival: 14.0 months for Ra-223 vs 11.2 months for
placebo [2-sided P=0.00185; HR=0.695; 95% CI: 0.552, 0.875]).
Ra-223 had a favorable safety profile across these trials. In
ALSYMPCA, there was a low incidence of myelosuppression with
Ra-223 (grade 3/4 neutropenia: 1.8% vs 0.8% in Ra-223 and
placebo groups, respectively).
Conclusions: Ra-223 shows a survival benefit and a favorable
safety profile in CRPC patients with bone metastases. Ra-223 is
easy to use, and few radiation restrictions are required.
3
Extension of lymph node dissection can increase progressionfree survival in patients with intermediate and high risk
prostate cancer
Andrianov AN, Alekseev BY, Nyushko KM, Vorobyev NV. Urology, Moscow Hertzen
Oncology Institute, Moscow, Russian Federation
Introduction & Objectives: Recent clinical data have
established that standard pelvic lymph node dissection (S-PLND)
in prostate cancer (PC) patients is less accurate in assessing
lymph node (LN) metastases than extended (E-PLND). Several
studies have demonstrated that E-PLND could enhance survival,
although this question is on the debate because of absence of
data of randomized studies. The aim of the study was to evaluate
biochemical progression-free survival (PFS) in intermediate and
high risk PC patients who had undergone radical prostatectomy
(RPE) and PLND.
Materials & Methods: Retrospective analysis of a database
from 595 patients after RPE and PLND since 2006 till 2011 in
our institution was performed. 288 consecutive patients with
intermediate and high risk PC (PSA >10 ng/ml, clinical stage
≥T2b, biopsy Gleason score ≥7, percentage of positive biopsy
cores ≥50%) were included for analysis. According to anatomical
regions of PLND performed, patients were divided into 3 groups:
S-PLND was performed in 39 (13.5%) patients; E-PLND – in 137
(47.6%) and super extended PLND (SE-PLND) – in 112 (38.9%)
patients. LN metastases were verified in 2 (5.1%), 26 (18.9%)
and 38 (33.9%) patients respectively (p=0.003). Patients with
LN metastases were excluded from the further survival analysis.
Mean number of LN removed was 13.6±6.9 (4-31); 23.3±7.2
(12-56) and 29.1±7.9 (15-52) respectively (p<0.0001); mean PSA
level was 11.1±5.6 ng/ml; 13.7±9.3 ng/ml and 16.4±10.6 ng/
ml respectively (p=0.04); mean percentage of positive biopsy
cores was 43.4±27.5%; 47.2±23.9% and 55.2±27.3% respectively
(p=0.05). Biopsy Gleason score was significantly more favorable
in the S-PLND group of patients (p=0.0002). Biochemical
recurrence was assessed as elevation of PSA >0.2 ng/ml on 3
consecutive measurements.
in the E-PLND and in 8 (10.8%) patients in the SE-PLND group.
Cumulative 3-year PFS rate was 64.6±10.1% for patients in the
S-PLND group, 84.4±7.7% in the E-PLND group and 81.49±9.9%
in the SE-PLND group (p=0.035). More extended PLND with
removing >20 LN was associated with significantly increasing
PFS rates. Comparing cumulative 38-month PFS in subgroup of
patients with ≤10 and >20 LN removed, PFS rates were 36.9% and
76.5% respectively (p=0.003).
Conclusions: E-PLND and SE-PLND are more accurate for LN
staging in PC patients. S-PLND is associated with worse survival
and should not be performed in cases of intermediate and high
risk PC. Extensive E-PLND and SE-PLND with removing >20 LN
could be recommended in this group of patients to achieve better
PFS.
4
Results of pathohistological examination in clinically high-risk
prostate cancer patients undergoing radical prostatectomy
Musch M1, Roggenbuck U1, Plümmer J2, Klevecka V2, Kröpfl D2. 1Institute of Medical
Informatics, Biometry and Epidemiology, University of Duisburg-Essen, Essen,
Germany; 2Department of Urology, Paediatric Urology and Urological Oncology,
Kliniken Essen-Mitte, Essen, Germany
Objectives: We analyzed the results of pathohistological
examination in patients with clinically high-risk prostate
cancer (PCA) following radical prostatectomy to determine the
proportion of patients eventually presenting overall favorable
tumor characteristics (OFTC) (i.e. pT2a-c and Gleason score ≤7a
and pN0).
Methods: Between 01/06/1997 and 31/10/2011 2346 patients
with biopsy detected PCA underwent radical prostatectomy in
our institution. According to D’Amico criteria 1767 patients
presented low- (n=962) or intermediate-risk (n=805), and
579 high-risk PCA. The pathohistological findings of the
prostatectomy specimens were compared between low-/
intermediate-risk versus high-risk patients, and between
patients with different high-risk factor constellations.
Results: High-risk PCA patients showed significantly more nonorgan-confined PCA (74.8% vs. 36.6%; p<0.0001), prostatectomy
Gleason scores ≥7b (53.0% vs. 13.8%; p<0.0001), lymph node
metastases (28.7% vs. 4.9%; p<0.0001), and positive surgical
margins (50.2% vs. 27.3%; p<0.0001) when compared to low-/
intermediate-risk PCA patients. Accordingly, high-risk patients
were less likely to harbor OFTC (17.3% vs. 58.2%; p<0.0001).
Conversely, that means, however, that nearly every 5th patient
assumed to be at high risk of disease progression following
radical prostatectomy indeed has favorable and most likely
curable PCA. Especially the subgroup of patients with PSA
>20 ng/ml or cT2c-3 tumor as sole high-risk factor showed a
considerable proportion of OFTC in 30.2% and 26.1% of cases,
respectively. Contrary, patients with biopsy Gleason scores 8-10
as sole high-risk factor were associated with OFTC in only 8.6%
of cases. Thus, the latter patients had a likewise low rate of OFTC
as had patients with two (3.7-8.0%) or three high-risk factors
(3.4%).
Conclusions: Nearly every 5th patient assumed to be clinically
at high risk of PCA progression following radical prostatectomy
indeed had OFTC. Particularly patients with PSA >20 ng/ml or
cT2c-3 tumor as sole high-risk factor were misclassified.
Results: Median follow up time was 25 months (3-72 months).
During this period biochemical recurrences were observed in
10 (27%) patients in the S-PLND group, in 13 (11.7%) patients
abstracts ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������� 27
Abstracts accepted for oral
presentation poster session
Minor postoperative complications
Urinary tract infection
N=140 (4%)
Re-cystogram (extravasation)
N=110 (3.1%)
Retention after catheter removal
N=46 (1.31%)
Abdominal pain
N=32 (1%)
Fever
N=20 (0.6%)
Solder pain
N=18 (0.6%)
Constipation
N=17 (0.6%)
Perivesical hematoma
N=15 (0.5%)
5
Asymptomatic lymphocele
N=12 (0.4%)
Scrotal edema
N=10 (0.3%)
Intraoperative and postoperative complications encountered
in patients undergoing robotic-assisted laparoscopic radical
prostatectomy. An analysis of 3500 consecutive cases
Bladder coagel evacuation
N=9 (0.3%)
Allergy
N=9 (0.3%)
Bladder tenismus
N=9 (0.3%)
Arrhythmia
N=8 (0.2%)
Scrotal hematoma
N=6 (0.2%)
Penis edema
N=6 (0.2%)
Port site infection
N=6 (0.2%)
Acute epididymitis
N=6 (0.2%)
Subcutaneous emphysema
N=6 (0.2%)
Materials & Methods: The records of N=3500 men who
underwent RALP from February 2006 to February 2012
were retrospectively reviewed. All patients were assessed
for intraoperative as well as postoperative complications.
Postoperative complications and re-interventions encountered up
to 30 days postoperatively stratified by the Clavien classification
and were characterized as minor (Clavien’s grade I–IIIa) and major
postoperative complications (Clavien’s grade IIIb-IVa). Hemorrhage
was defined as greater than 500 ml blood loss during the operation.
Further parameters analyzed included: age, body mass index
(BMI), prostate size, PSA values, biopsy Gleason score, lymph node
dissection, and pathologic stage.
Hypotension
N=5 (0.1%)
Conjunctivitis
N=5 (0.1%)
Results: The intraoperative complications as well as minor and
major postoperative complications are listed in the Tables. The
median age of the patients was 64.2 years, median BMI was 26.6
kg/m2, median prostate weight was 41.3 gr. and median PSA
value was 10.1 ng/ml. The Gleason biopsy score was Gleason <7 in
65% of cases, Gleason 7 in 34.6% and Gleason >7 in 9.4% of cases.
Lymph node dissection was performed in 75.6% of cases. An organconfined disease was noted in 75.2% of cases and extraprostatic
extension in 24.8%. The overall intraoperative complication rate was
4.9%, the overall minor postoperative complication rate was 16.1%
and the overall major postoperative complication rate was 1.8%.
6
Conclusions: RALP is not free of complications. Nevertheless in
experienced hands it can be considered as a safe surgical procedure
with very low morbidity and mortality.
10 years experience: permanent prostate implant (PPI) and
iodine 125 (I125) seeds
Moderated poster sessions will take place in Auditorium 3 and in
meeting room 4 at the Riverside wing during the lunch breaks on
Thursday and Friday, For detailed programme see live screens or
http://live.prosca.org
Labanaris AP, Zugor V, Wagner C, Witt JH. Urology, Prostate Center Northwest, St.
Antonius-Hospital, Gronau, Germany
Objectives: To assess the intraoperative and postoperative
complications encountered in patients undergoing robot-assisted
laparoscopic radical prostatectomy (RALP) by analysing 3500
consecutive cases.
Intraoperative complications
Anastomosis insufficiency
N=65 (1.85%)
Hemorrhage
N=44 (1.4%)
Technical problems of the system
N=10 (0.3%)
Tearing of the anastomosis suture
N=10 (0.3%)
Small intestine injury
N=8 (0.2%)
Rectum injury
N=7 (0.2%)
Bladder perforation
N=7 (0.2%)
Large intestine injury
N=5 (0.1%)
Tearing of the anastomosis
N=5 (0.1%)
Defect robot arm
N=5 (0.1%)
Ureter injury
N=1 (0.03%)
Obturator nerve injury
N=1 (0.03%)
Major postoperative complications
Re-operations (Overall)
Hematoma
Intestine lesions
N=46 (1.31%)
N=18 (0.51%)
N=7 (0.2%)
Abscess
Port site hernia (0.2%)
Windowing of lymphocele
Dehiscence of the fascia with closure
Nephrostomy
N=4 (0.1%)
N=6 (0.2%)
N=4 (0.1%)
N=4 (0.1%)
N=2 (0.05%)
Secondary rupture of the anastomosis
N=18 (0.51%)
Acute renal failure
N=3 (0.1%)
Adult respiratory distress syndrome
N=2 (0.05%)
Stroke
N=2 (0.05%)
Myocardial Infarct
N=2 (0.05%)
Cardiac arrest
N=1 (0.03%)
Burette R1, Bourgois N1, Corbusier A 2, Germeau F2, Hamal M1,3, Audia S1,3, Van Leer P2.
1
Radiotherapy, CHIREC, Brussels, Belgium; 2Urology, CHIREC, Brussels, Belgium;
3
Physics, CHIREC, Brussels, Belgium
Purpose: Since 2000, we prospectively record our experience
with I125 seeds PPI Mt Sinaï Real-Time° method proctoring as
these were available in Europe. The aim of this study is to report
the clinical results, benefit and side effects, the progresses made
in the technology of various types of I125 seeds retrospectively
compared still using Real-Time° method. Dose constraints aimed
at increasing V100p D90p and reducing V150p D30u. Better CTV
coverage and OAR shielding were to enhance disease control and
decrease urinary and sexual dysfunction.
Materials & Methods: From September 2000, 512 low-risk
and intermediate-risks patients were treated by PPI in various
institutions. 408 home patients were followed and 391 (95.8%)
28 ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������ abstracts
were evaluable for bFFF survival (PSA <1 ng/ml). For some
patients, QoL through IPSS score, QLQ-C30, CTAC AE were
retrospectively analyzed at 1 year. Dosimetrical optimized
data were correlated with clinical evolution. ABS-ESTRO
recommendations were matched pre and post operatively by a
US-CT scan at 1 month, some cases at 3-6 months. Migration of
seeds was tracked by seed finder fusion software at the same time
in order to quantify contributions to dose constrains with these
different seeds.
Results: Improvement of V100p from a mean of 95% to more
than 98% confirmed better post planning dose coverage of
prostate CTV volume significantly due to more peripheral
implantation of seeds. All the patients had a minimum D90p of
more than 155 Gy with a mean of 175.3 Gy. Reduction of V150p
from a mean of 65% to 52 % as D30u from a mean 195 Gy to less
than 175 Gy (11%) was also correlated with additional effect of
more peripheral positioning and reduction of seeds migrations in
the central area.
Rectal wall sparing was confirmed by V100r systematically
inferior to 1.30 cc with a mean of 0.80 cc and was never a
clinical problem. Contribution of new coated seeds to migration
reduction is under investigation on quality of implant compared
to historical technique. With a mean follow-up of 86.4 months,
8 patients died and only 2 from PCa (2.05%). 26 biological
recurrences (6.65%) were analysed out of which 20 were GS VII
with a bFFF of 93.35%. Recurrences were mainly localized in
lymphatic nodes combined or not with metastasis. 7 patients
experienced secondary cancers; 20 cardiovascular diseases.
Conclusions: In this retrospective 10-years study, we can
confirm, like other teams, that PPI in PCa is a highly effective
treatment. Technology enhancements in seeds development and
positioning is giving a clear geometrical and technical clinical
impact to patient’s disease control and reduction of side effects.
PPI is a good option in selected indications for favorable- or
intermediate-risk prostate cancers associated with maintenance
of a good urinary and erectile function.
7
Septicaemia after transrectal biopsy of the prostate: a 6-year
analysis of 2400 biopsies
Holmes MA, Bary P, Smit-Archer L, Devcich G, Leyland J. Urology, Waikato Hospital,
Hamilton, New Zealand
Introduction & Objectives: All patients who underwent a
transrectal ultrasound guided (TRUS) prostate biopsy between
2006 and 2011 under local anaesthetic were reviewed to
assess the annual sepsis rate, causative organisms, antibiotic
sensitivities, identify any obvious possible pre-existing risk
factors and confirm an appropriate empirical antibiotic regime
for post TRUS prostate septicaemia.
Patients & Methods: All hospital admissions for urosepsis
occur at 1 large regional hospital. Draining secondary hospitals
share a common database. A single private lab is the sole provider
of pathology services to the region. 12 core prostate biopsies,
without an enema, are performed under a standard ciprofloxacin
prophylaxis regime. Admissions were identified by 3 mechanisms
including an individual review of each patient’s pathology and
hospital data around the time of their biopsy. Interim results for
2007-2010 have been previously published.
Results: 2513 patients underwent a TRUS of the prostate. 2337
patients had a TRUS guided biopsy. 22 patients were admitted
with urosepsis (0.94%). Sepsis rates were 0.3% in 2006 and 2007,
1.1% in 2008, 1.2% in 2009, 0.8% in 2010 and 1.8% in 2011. E.
Coli was isolated in 19/22 cases. No organism was isolated in
3/22 cases. 58% of isolates were ciprofloxacin resistant, 36%
gentamicin resistant and 10% augmentin resistant. No isolates
were meropenem resistant. No ESBL activity was identified.
Augmentin and gentamicin would have covered 90% of E.Coli
identified. Statistical analysis noted a marginally significant
increase in sepsis rates over time. The significance of this is
unclear.
Discussion: Only E. Coli was identified as the cause of sepsis.
Isolates were often but not always ciprofloxacin resistant.
One in 3 isolates were resistant to gentamicin. Screening for
ciprofloxacin resistance in rectal flora may therefore reduce some
of the septic episodes but not all. It is still unclear after analysing
6 years of biopsy data whether the sepsis rate is increasing.
This reflects the relatively rare nature of the event. No obvious
underlying risk factors were identified.
Conclusions: Ciprofloxacin prophylaxis remains an appropriate
regime for prostate biopsy. Evidence of an increasing rate over
time of sepsis post TRUS guided prostate biopsy may have
been identified. An empirical antibiotic choice of gentamicin
and augmentin would have covered 18/19 and meropenem all
identified E.Coli causes of septicaemia.
8
A decade of high intensity focused ultrasound in prostate
cancer, long-term oncologic results: a single centre experience
Holz S, Limani K, Peltier A, Hawaux E, van Velthoven R. Urology, Institut Jules Bordet,
Bruxelles, Belgium
Introduction: The management of localized prostate cancer
is evolving and controversial. Established treatment options
include radical prostatectomy, radiation therapy and active
surveillance. These treatments may induce complications or
emphasize patient’s anxiety; therefore minimally-invasive
alternative treatments are emerging. High intensity focused
ultrasound (HIFU) is an emerging alternative to established
standard of care, especially in heavily comorbid and elderly
patients.
Methods: We retrospectively evaluated all patients treated with
global HIFU as primary curative therapy for prostate cancer in
our institution, including those who have received neo-adjuvant
hormone therapy. From September 2001 to December 2010 a
total of 100 patients were treated with global HIFU. We excluded
patients with follow-up inferior to 1 year (4 patients) and
patients with incomplete oncologic data (5 patients). 91 patients
were included for statistical analysis. Evaluated end points were;
overall, cancer-specific and metastasis-free survival as well
as biochemical recurrence-free survival using Astro Phoenix
definition (PSA nadir + 2.0 ng/mL) and Stuttgart definition (PSA
nadir + 1.2 ng/mL).
Results: Median age was 75 years (range: 61-87). Gleason biopsy
distribution was: 66% less than 7, 24% of 7 and 10% higher
than 7. Mean and median PSA were: 11.32 +/- 9.94 ng/mL and
8.37 respectively. T-stage: 51% T1, 45% T2, 4% T3. D’Amico
risk stratification: 34% low, 46% intermediate and 20% high.
Median actuarial follow-up was 7.25 years. At 5 and 10 years the
estimated median survival was: overall 89%-66%, cancer-specific
96%-84%, metastasis-free 85%-65%, biochemical recurrencefree, Phoenix: 53%-34% and Stuttgart: 52%-29%. Statistically
significant univariate prognostic factors for biochemical
recurrence were: D’Amico high risk (p<0.05), pre-HIFU PSA
(p<0.0001) and PSA at nadir (p<0.0001).
abstracts ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������� 29
Discussion: HIFU remains a controversial treatment for
prostate cancer. In our series, high-risk patients performed very
poorly. Candidates for HIFU should be very carefully selected.
PSA at nadir seems to be a valid prognostic factor for biochemical
recurrence.
9
Positive surgical margin rates in patients undergoing bilateral
intrafacial nerve sparing robot-assisted laparoscopic radical
prostatectomy
Labanaris AP, Zugor V, Wagner C, Habibzada J, Witt JH. Urology, Prostate Center
Northwest, St. Antonius-Hospital, Gronau, Germany
Objectives: Although the past years robot-assisted laparoscopic
radical prostatectomy (RALP) has become profoundly popular,
especially due to the ability to preserve the neurovascular
bundles, some urologists remain sceptic regarding the lack of
tactile sensation and subsequently a possible increase of positive
surgical margins (PSM). The objective of this study is to evaluate
the PSM rates in patients undergoing bilateral intrafacial nerve
sparing (BINS) RALP prostatectomy.
Materials & Methods: The records of N=621 men who
underwent BINS RALP from February 2006 to August 2011
were retrospectively reviewed. None of the patients had
undergone any form of adjuvant therapy that would have
influenced the surgical margin status such as previous hormonal
therapy, external radiation, brachytherapy and HIFU therapy.
Additionally all stage T0 cancer patients were excluded from the
study. The parameters analysed included: age, prostate specific
antigen (PSA), prostate size, clinical stage, preoperative Gleason
score, pathologic stage, postoperative Gleason score, percent of
tumor, overall PSM rates and PSM rates according to pathologic
stage. BINS was performed in patients with a PSA level <10 ng/ml
and/or Gleason score <7 and/or in cases of only one positive core
biopsy of Gleason 7 and/or in clinical T1c-T2a tumors.
Results: The median age of the patients was 61.3 years old (range
39-75 years), the median PSA was 6.1 ng/ml (range 0.3-10 ng/ml),
the median prostate size was 39.3 gr. (range 10-130 gr.) and the
clinical stage was T1c in N=550 patients (88.5%) and T2a in N=71
patients (11.5%). The preoperative Gleason score was Gleason <7 in
N=495 patients (79.7%) and Gleason 7 in N=156 patients (20.3%).
The overall PSM rate was 4.5% (N=28 patients). PSM were noted
in 3.2% of all T2 cases (19 of 577 T2 patients). PSM were evident
in N=1 patient with a T2a tumor (0.15%), in N=2 patients with a
T2b tumor (0.3%) and in N=16 patients with a T2c tumor (2.7%).
PSM were noted in 22.7% of all T3 cases (10 of 44 T3 patients).
N=9 exhibited PSM with a T3a tumor (20.4%) and N=1 patient
PSM with a T3b tumor (2.27%). No stage T4 cases were evident.
Conclusions: Our findings suggest that patients eligible for
bilateral intrafacial nerve sparing robot-assisted laparoscopic
radical prostatectomy exhibit an excellent surgical margin
status. In cases were the pathologic examination reveals
an extracapsular extension the surgical margin status is
compromised.
10
Positive surgical margins in robotic prostatectomy: are they
important and are they predictable?
Brett A, Khan Y, Corbishley C, Issa R, Perry M, Anderson C. Urology, St George’s
Hospital, London, United Kingdom
30
Introduction: Achieving clear margins in robotic prostatectomy
is expected to improve oncological outcomes. We looked at the
impact of focal (fPSM: single and <5mm) and extensive positive
margins (ePSM: multiple or ≥5mm) and attempted to identify
predictive factors.
Patients & Methods: Prospective data collection enabled the
identification of an intermediate risk group (any Gleason 7 or
PSA 10-20 or pT2b or T2c) for analysis. Low risk category patients
(Gleason ≤6 & PSA <10 & T2a) were excluded as all had clear
margins and successful outcome. Mean follow up was 14.72 months
(6-40). End points were defined as surgical success (PSA ≤0.1);
surgical failure (PSA >0.1) and adjuvant radiotherapy. We compared
the PSM group to 49 case-matched patients with negative surgical
margins (NSM).
Results: 44 patients had positive surgical margins (PSM). There
was no significant difference in PSA (p=0.9997) and Gleason
score (p=0.9960) in the PSM and NSM groups.
Surgical failure was seen in 4% of NSM and 18% of all PSM
(p=0.04). However, on sub-group analysis of PSM the surgical
failure rate was 8% of fPSM (p=0.49) and 22% of ePSM (p=0.022).
There was a significant difference in cancer volume between NSM
and all PSM (p=0.0002), fPSM (p=0.0225) and ePSM (p<0.0001).
There was also a significant difference in prostate size between
NSM and fPSM (p=0.0409).
Conclusions: In the intermediate risk group there was no
significant outcome difference in patients with fPSM and NSM.
The only important factor predicting PSM was cancer volume
confirming the need for careful preoperative case selection.
11
Influence of nerve sparing surgery (NS) on (post)operative
outcome, quality of life, oncological and functional results
following robot assisted laparoscopic radical prostatectomy
(RALP)
Collette ERP1, Rambaran SS1, Kliffen M2, Engel RP1, Klaver OS1. 1Urology, Maasstad
Hospital, Rotterdam, Netherlands; 2Pathology, Maasstad Hospital, Rotterdam,
Netherlands
Introduction: Analysis on influence and safety of NS on
(post)operative outcome, quality of life (QoL), oncological and
functional results 1 year after RALP.
Materials & Methods: Prospective data analysis of 416 patients
(pts) who underwent bilateral NS RALP (BilNS) (n=227) vs.
unilateral NS RALP (UniNS) (n=113) vs. non nerve sparing
RALP (NonNS) (n=76) between January 2009 and March
2011. Evaluated parameters: complications, positive surgical
margins, PSA recurrence, QoL, continence and potency after
1 year. Continence and potency were measured by validated
questionnaires (ICIQ-SF-UI and SHIM-IIEF-5).
Results: Table 1 shows pt characteristics. No significant
difference in number of complications between BilNS vs. UniNS
vs. NonNS was seen (8 vs. 6 vs. 11%; p=0,56). Percentage positive
surgical margins was not significantly different (16 vs. 15 vs.
18%; p=0,82; n=416), also within the pT2 group (13 vs. 10 vs. 8%;
p=0,59; n=303). After BilNS PSA recurrence was significantly less
compared to UniNS en NonNS (9 vs. 14 vs. 20%; p=0,04; n=397).
Recovery of potency in preoperative potent pts was significantly
superior after BilNS vs. UniNS and NonNS (61 vs. 12 vs. 6%;
p<0,01; n=232). Recovery of continence was not significantly
different (90 vs. 84 vs. 85%; p=0,28; n=366) as well as QoL (90 vs.
83 vs. 80%; p=0,07; n=385). In multivariate analysis BilNS was
������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������
abstracts
the best predictor of potency (p<0,01; n=340; HR=20,58; 4,5293,67 95% C.I.). No significant association was found between
NS and continence or oncological outcome. BilNS was the best
predictor of QoL (p<0,01; n=371; HR=4,17; 1,69-10,24 95% C.I.).
Conclusions: NS seems oncological safe; no significantly
increased risk for positive surgical margins, PSA recurrence
or complications was demonstrated in our series. BilNS is
significantly associated with beter potency outcome, our
cohort showed no significant difference regarding continence.
In multivariate analysis significant difference in QoL was
demonstrated, in favor of BilNS.
positive node status hormonal treatment. After a median follow
up period of 11 months (range 3-31 months) none of the patients
exhibited biochemical progression.
Conclusions: Our findings suggest that the clinical stage of
these patients does not reflect their pathologic stage. Patients
should be informed that there is a great risk of exhibiting more
aggressive tumors as preoperatively thought.
13
Surgical outcome of robot-assisted radical prostatectomy after
a training program in a high-volume robotic centre
Lumen N1, De Troyer B1, Fonteyne V2, Decaestecker K 1, De Meerleer G2, Oosterlinck W 1,
Ost P2, Van Praet C1, Mottrie A3. 1Urology, Ghent University Hospital, Ghent, Belgium;
2
Radiotherapy, Ghent University Hospital, Ghent, Belgium; 3Urology, OLV Clinic, Aalst,
Belgium
12
Clinicopathological characteristics and oncological outcomes
of patients undergoing robot-assisted laparoscopic radical
prostatectomy for prostate cancer after previous treatment
with 5-alpha-reductase inhibitors for benign prostatic
hyperplasia
Labanaris AP, Zugor V, Wagner C, Witt JH. Urology, Prostate Center Northwest, St.
Antonius-Hospital, Gronau, Germany
Objectives: 5-alpha-reductase inhibitors (5ARI) are a well
accepted treatment for men with benign prostatic hyperplasia
(BPH). Nevertheless a cohort of these patients will exhibit
prostate cancer (PCa) at some point in their life. The aim of this
study is to evaluate the clinicopathological characteristics and
oncological outcomes of patients undergoing robot-assisted
laparoscopic radical prostatectomy (RALP) for PCa after previous
treatment with 5ARI for BPH.
Materials & Methods: The records of N=36 men who underwent
RALP from February 2006 to June 2011 were retrospectively
reviewed. All patients previous to PCa detection have had
previous treatment with 5ARI for BPH for at least 1 year. The
parameters analyzed included: age, PSA values, prostate size,
clinical stage, biopsy Gleason score, pathologic stage, Gleason
score of prostate specimen, percentage of PCa found in the
prostate specimen, positive margin status (PSM), lymph node
status and biochemical progression in the follow up period,
defined as PSA ≥0.2 mg/dl after nadir or never reached nadir.
Results: The average time of previous treatment with 5ARI for
BPH was 36.4 months (range 12-120 months). The median age
of the patients was 63.7 years old, the median PSA was 9.3 mg/
dl and the median prostate size 44.1 ml. The clinical stage was
T1c for 52.7% of patients, T2a for 25%, T2b for 19.4% and T2c for
2.7%. The Gleason biopsy score was Gleason <7 in 52.7% of cases,
Gleason 7 in 41.6% and Gleason >7 in 5.5%. The Gleason score of
the prostate specimen was upgraded in 30.5% of cases. A Gleason
<7 pattern was evident in 44.4% of cases, Gleason 7 in 19.4%
and Gleason >7 in 36.1%. The pathologic stage was T0 in 8.3% of
cases, T2 in 72.2%, T3 in 16.6% and T4 in 8.3%. The percentage
of PCa found in the prostate specimen was 14.9% and PSM were
encountered in 11.1% of patients. Lymph nodes were removed
in 77.7% of cases and were positive in 8.3%. All patients with
PSM and T3-T4 PCa underwent radiation after RALP and all with
Objectives: Robot-assisted radical prostatectomy (RARP) is
an excellent technique in the treatment of prostate cancer but
requires substantial surgical skills. A training program that
allows the robot-surgeon to obtain these skills can overcome
the problem of a learning curve. This report aims to evaluate the
value of such a training program.
Materials & Methods: Before starting RARP, a young urologist
followed a 6-month training program at a high-volume robotic
centre. The surgical outcome of the first 50 RARPs are evaluated
and compared with a cohort of 50 open radical prostatectomies
(ORP) performed by an experienced senior urologist during
the same period. An independent t-test was performed for
continuous variables and a chi-square test for categorical
variables. Values were presented as mean (± standard deviation).
Tumor stage and grade were similar in both groups. Nervesparing (uni- or bilateral) was significantly more performed with
RARP. Follow-up duration was significantly longer in ORP.
Results: Operation time was similar in both groups. Hospital
stay was on average almost 1 day shorter with RARP.
Catheterization duration was significantly shorter (8,6 days
(± 6,9) vs. 15,2 (± 5,2); p<0.0001) and decline in Hb was
significantly less in RARP (2,10 g/dl (± 1,09) vs. 4,03 (± 1,17);
p<0.0001). Complication rate was not significantly different
among groups but tended to be more severe in ORP. Positive
surgical margin rate was 6% and 24% for respectively RARP and
ORP (p=0.022). At 12 months, urinary continence was 81 and
82,9% for respectively RARP and ORP (p=1).
Conclusions: These data indicate that a training program in a
high-volume robotic centre can reduce the learning curve. RARP
was associated with significantly less positive surgical margins,
shorter catheterization duration and less blood loss compared to
ORP.
14
Limited versus extended pelvic lymph node dissection in
prostate cancer patients
Maes H1, Van Praet C1, Ost P2, Villeirs G3, De Meerleer G2, Fonteyne V2, Lumen N1.
1
Urology, University Hospital Ghent, Ghent, Belgium; 2Radiotherapy, Ghent University
Hospital, Ghent, Belgium; 3Radiology, Ghent University Hospital, Ghent, Belgium
Objectives: Pelvic lymph node dissection (PLND) is currently
the most reliable method for staging prostate cancer patients for
lymph node metastases. Patients opting for primary external
beam radiotherapy undergo a prior staging PLND at our centre
abstracts ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������� 31
based on the risk of lymph node involvement as calculated with
Roach’s formula. There is evidence that the increase in lymph
nodes removed increases staging accuracy. The aim of this study
is to compare the number of lymph nodes removed by limited
PLND, removing only the nodes from the obturator fossa, versus
extended PLND which comprises removal of at least the nodes
from the obturator fossa and along internal and external iliac
artery. Complications of both techniques are also compared.
an age and sex matched control cohort (Figure – broken line). The
curve for patients with 0<BSI<=1 was closer to the BSI=0 curve
than the corresponding BSI>1 curve, indicating that the tumor
burden is important and not only the presence of metastases. In
a multivariate survival analysis BSI was associated with survival
(Hazard Ratio, 1.25; P<0.001). The Concordance index increased
from 0.66 to 0.73 when adding BSI to a model containing clinical
stage, PSA and Gleason score.
Materials & Methods: In this retrospective analysis, 102
patients had a PLND between 2006 and 2011 prior to primary
external beam radiotherapy. Postoperative radiographic imaging
with CT and MRI performed for radiotherapy planning was
used to detect lymphocoeles. We compared limited (n=26) vs.
extended (n=76) PLND with regards to retrieval of lymph nodes
using student t-test and complications using Fisher’s exact test.
Values were expressed as mean (± standard deviation). Except for
4 laparoscopic cases, all limited PLNDs were performed open, and
65 of 76 extended PLNDs were performed laparoscopically.
Conclusions: These data show that BSI can be used as a
complement to PSA to stratify high risk prostate cancer patients
at the time of diagnosis. BSI may play a role for the decision
when to start hormonal therapy in advanced asymptomatic
prostate cancer patients. The risk or expected median survival
time based also on BSI analysis may be of value, for example, to
advice patients with a strong wish to avoid treatment-related
side-effects.
Results: With extended PLND a mean of 16,4 (± 7,8) lymph
nodes were removed vs. 9,3 (± 4,3) with limited PLND (p<0.0001).
Mean operation time was longer for the extended group (130 (±
38) vs. 89 (± 51) minutes; p=0.007) but mean hospital stay was
shorter (4 (± 2,2) vs. 5,8 (± 2,0) days; p=0.0004). Perioperative
and postoperative complications were similar for extended vs.
limited PLND (5,2% vs. 2,7%; p=1 and 27,6% vs. 34,6%; p=0.66
respectively). Symptomatic lymphocoeles were observed in 7,9%
after extended PLND vs. 15,4% after limited PLND (p=0.27),
whereas radiographic lymphocoeles were seen in 56,6% vs. 50,0%
respectively (p=0.72).
Conclusions: In our series laparoscopic extended pelvic lymph
node dissection allows for retrieval of almost twice the amount
of lymph nodes, thus increasing staging accuracy, with a very
limited increase in peri- and postoperative complications and
radiographic lymphocoeles. It is a safe and effective technique to
stage prostate cancer patients for lymph node involvement.
16
Trifecta rates and surgical margins; results and learning curve
after robot assisted laparoscopic radical prostatectomy (RALP)
Collette ERP1, Rambaran SS1, Kliffen M2, Engel RP1, Klaver OS1. 1Urology, Maasstad
Hospital, Rotterdam, Netherlands; 2Pathology, Maasstad Hospital, Rotterdam,
Netherlands
15
Risk stratification at the time of diagnosis based on bone scan
index
Kaboteh R , Damber JE , Gjertsson P , Höglund P , Lomsky M , Ohlsson M ,
Edenbrandt L1. 1Dept. of Molecular and Clinical Medicine, Sahlgrenska University
Hospital, Gothenburg, Sweden; 2Dept. of Urology, Institute of Clinical Sciences,
Gothenburg University/Sahlgrenska University Hospital, Gothenburg, Sweden;
3
Competence Centre for Clinical Research, Lund University Hospital, Lund, Sweden;
4
Dept. of Theoretical Physics, Lund University Hospital, Lund, Sweden
1
2
1
3
1
4
Purpose: Bone scan index (BSI) is a method of expressing the
tumor burden in bone as a percent of the total skeletal mass.
BSI has been proposed as a response biomarker in castrationresistant metastatic prostate cancer. The purpose of this study
was to explore BSI as a prognostic biomarker in a group of high
risk prostate cancer patients at the time of diagnosis.
Patients & Methods: This retrospective study was based on 183
consecutive prostate cancer patients, who had undergone wholebody bone scans at the time of diagnosis and who were classified
as high risk patients, i.e. at least one of the following criteria were
fulfilled: T stage (T2c/T3/T4) or Gleason score (8-10) or PSA >20
ng/mL. BSI was calculated using an automated method.
Results: The 5-year probability of survival for all patients was
54% and when this group was subdivided into the groups BSI=0,
0<BSI<=1 and BSI>1, the corresponding 5-year probabilities of
survival were 79%, 64%, and 12%, respectively. The Kaplan-Meier
curves for patients with BSI=0 and 0<BSI<=1 were close to that of
Introduction: Analysis of results and learning curve of trifecta
rates and surgical margins; 1 year after RALP.
Materials & Methods: Prospective data analysis of 416 patients
(pts) who underwent RALP between January 2009 and March
2011. PSA rise (PSA ≥ 0,2) was used as surrogate endpoint for
progression. Continence and potency were measured by validated
questionnaires (ICIQ-SF-UI and SHIM-IIEF-5). All operations
were performed by 1 surgeon. Pts were classified in chronological
cohorts of 50 pts. Trifecta was defined as no PSA recurrence,
continent and potent.
Results: Total cases: 416. Mean age: 64,6 years. Overall positive
surgical margin rate was 16% (67/416 pts); in the pT2 group 12%
(35/303) and in the pT3 group 28% (32/113). After 1 year 12%
(48/397) of pts experienced no PSA recurrence. 86% (332/385)
of pts experienced good quality of life. Of all preoperative potent
pts, 61% (83/136) remained potent after bilateral nerve sparing
surgery. After 1 year 87% (320/366) of pts were continent.
Trifecta was reached in 59% (81/138) of all pts. Figure 1 shows
percentage of negative surgical margins per series of 50 pts.
Negative surgical margin rate in the pT2 group was 76%, 79%,
80%, 91%, 100%, 97%, 90%, 92% for respectively patient 1-50,
51-100, 101-150, 151-200, 201-250, 251-300, 301-350 en 351-400.
Combination of “no PSA recurrence” and continence was 72%,
78%, 67%, 83%, 71%, 83%, 73%, 81%. Trifecta was reached in
60%, 56%, 53%, 50%, 58%, 84%, 58%, 50% of pts. The number of
negative surgical margins of pts in the pT2 group shows a rising
trend, which stabilizes after 150 procedures.
32 ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������ abstracts
Conclusions: RALP is a safe and feasible intervention with
acceptable learning curve. After approx. 150 procedures negative
surgical margins rise above 90% in the pT2 group. Regarding
trifecta or PSA recurrence in combination with continence, our
cohort of the first 400 procedures established no clear trend.
Conclusions: We assessed LNI in patients which underwent
LPLND because of prostate cancer. In the low risk group none had
LNI, in the intermediate risk group 13 (8%) patients had LNI and
in the high risk group 59 (30.7%) patients had LNI.
18
Robot-assisted laparoscopic radical prostatectomy in patients
with PSA levels ≥50 ng/ml. Surgical and oncologic outcomes
Labanaris AP, Zugor V, Wagner C, Addali M, Witt JH. Urology, Prostate Center
Northwest, St. Antonius-Hospital, Gronau, Germany
Objectives: To assess the surgical and oncologic outcomes in
patients with preoperative PSA levels ≥50 ng/ml undergoing
robot-assisted laparoscopic radical prostatectomy (RALP) for
prostate cancer (PCa).
17
Lymph node involvement after laparoscopic pelvic lymph node
dissection: a retrospective analysis of 391 cases
van Dooren VPM, Fossion LMCL. Urology, Maxima Medisch Centrum, Veldhoven,
Netherlands
Introduction: Despite current use of MRI for lymph node staging,
pelvic lymph node dissection (PLND) is still the gold standard to
stage patients with prostate cancer. The EAU guidelines define
three risk groups of lymph node involvement (LNI): the low risk
group is stage cT1-cT2a, has a Gleason score ≤ 6 and PSA < 10 ng/
ml; the intermediate risk group is stage cT2b-cT2c, has a Gleason
score 7 and PSA 10-20 ng/ml; the high risk group is stage cT3a
and above, has a Gleason score 8-10 and a PSA > 20 ng/ml.
Methods: We analyzed 391 patients (325 (83.1%) in center one
and 66 (16.9%) in center two) who underwent a laparoscopic
pelvic lymph node dissection (LPLND) from January 2000
until March 2012 in two general hospitals located in the
Netherlands. The LPLNDs were done according the current
standard LND template and were performed by three urologists.
206 (52.7%) patients received an endoscopic extraperitoneal
radical prostatectomy (EERPE) in combination with a LPLND.
33 (8.4%) patients were treated with brachytherapy, 111 (28.4%)
patients with external beam radiation therapy (EBRT), 40
(10.2%) patients with hormonal therapy and one (0.3%) patient
with high-intensity focused ultrasound (HIFU). Clinical stage,
preoperative PSA, Gleason score and positive biopsy cores were
assessed. Lymph node samples were assessed by two pathology
centers. Center one assessed 325 lymph node samples and center
two assessed 66 lymph nodes. We divided the groups according
to the risk groups stated in the EAU guidelines for prostate
cancer.
Results: Mean age was 65 years. Mean lymph node count was
11 LN. 72 (18.4%) patients out of the 391 patients had lymph
node involvement (LNI). LNI was seen in 8 (6.3%) patients with
clinical stage cT1-cT2a and LNI was seen in 64 (24,3%) patients
with clinical stage ≥ cT2b. 34 (17%) patients with LNI had
Gleason score < 6 and 38 (19.9%) patients with LNI had Gleason
score > 6. LNI was seen in 11 (8.5%) patients with PSA < 10 and
in 61 (23.4%) patients with PSA ≥ 10. None of the patients in the
EAU low risk group had LNI. In the intermediate risk group 13
(8%) patients had LNI, in the high risk group 59 (30.7%) patients
had LNI.
Materials & Methods: The records of N=36 men who underwent
RALP from February 2006 to July 2011 were retrospectively
reviewed. All patients had preoperative PSA levels ≥50 ng/ml.
The parameters analyzed included: age, prostate size, PSA values,
biopsy Gleason score, clinical stage, pathologic stage, Gleason
score of specimen, lymph node status, positive surgical margins
(PSM), percentage of PCa found in the specimen, blood loss,
skin-to-skin operative time, intraoperative complications, minor
and major complications, disease-specific mortality as well as
biochemical progression in the follow up period, defined as PSA
≥0.2 mg/dl after nadir or never reached nadir.
Results: The median age of the patients was 63.6 years old,
the median PSA was 86.1 mg/dl (range 50-220 mg/dl) and the
median prostate size 42.1 ml. The clinical stage was thought to
be confined in 77.7% of cases and locally extended in 22.3%.
The Gleason biopsy score was Gleason <7 in 19.4% of patients,
Gleason 7 in 41.6% and Gleason >7 in 38.9%. Intraoperative
complications were encountered in N=5 patients (13.8%), N=3
bilateral ureter stent insertion and N=2 rectum injury. Minor
postoperative complications were encountered in 25% of cases
and major in 5.5%. The median operative time was 154 min and
median blood loss 155 ml. The pathologic stage was T2 for 16.6%
of patients, T3 for 41.6% and T4 for 41.6%. A Gleason <7 pattern
was no longer evident, a Gleason 7 was evident in 41.6% of
patients and a Gleason >7 in 58.3%. The percentage of PCa found
in the prostate specimen was 63.6% and PSM were encountered
in 41.6% cases. Lymph nodes were removed in all cases and were
positive in 27.7% patients. N=30 patients (83.3%) underwent
adjuvant therapy, with N=18 cases (60%) undergoing radiation
therapy and N=12 (40%) hormonal treatment. After a median
follow up of 23.6 months (range 3–52 months) no disease-specific
mortality was evident but N=15 patients (41.6%) exhibited
biochemical progression.
Conclusions: Our findings suggest that RALP can be performed
in this cohort of patients. Nevertheless, patients should be
informed of the suboptimal oncologic outcomes as well as that it
is only one part of a multimodality therapy needed.
abstracts ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������� 33
19
The National Cancer Institute (NCI) Early Detection Research
Network (EDRN) urinary PCA3 validation trial
Wei JT 1, Sanda MG2, Thompson I3, Partin A4, Feng Z5, Sokoll L6, Groskopf J7, Brown E5,
Lotan Y8, Kibel AS9, Busby E10, Bidair M11, Lin D12, Taneja S13, Viterbo R14, Kagan J15,
Srivastava S15. 1Urology, University of Michigan , Ann Arbor, MI, United States;
2
Surgery, Beth Israel Deaconess Medical Center, Boston, MA, United States; 3Urology,
University of Texas Health Science Center, San Antonio, San Antonio, TX, United
States; 4Urology, Johns Hopkins Medical Institution, Baltimore, MD, United States;
5
Biostatistics and Biomathematics, Fred Hutchinson Cancer Research Center,
Seattle, WA, United States; 6Pathology, Johns Hopkins Medical Institution, Baltimore,
MD, United States; 7Gen-Probe Incorporated, San Diego, CA, United States; 8Urology,
University of Texas Southwestern Medical Center, Dallas, TX, United States; 9Surgery,
University of Washington St. Louis, St. Louis, MO, United Kingdom; 10Urology,
University of Alabama at Birmingham, Birmingham, AL, United States; 11San Diego
Clinical Trials, San Diego, CA, United States; 12Urology, University of Washington
Medical Center, Seattle, WA, United States; 13Urology, NYU Langone Medical Center,
New York, NY, United States; 14Surgical oncology, Fox Chase Cancer Center,
Philadelphia, PA, United States; 15Division of Cancer Prevention, National Cancer
Institute, Bethesda, MD, United States
Introduction & Objectives: Widespread use of PSA
screening has raised concerns of overdiagnosis of low-risk and
underdiagnosis of high-grade cancer. This is primarily due to the
low sensitivity and specificity of PSA. PCA3, a non-coding large
chain ribonucleic acid, is significantly overexpressed in cancer
tissue and quantitatively measured by a novel urinary assay. The
objective of this NCI EDRN trial was to conduct a comprehensive,
independent validation of the PROGENSATM PCA3 Assay for the
detection of prostate cancer.
Methods: A prospective, PROBE-compliant NCI validation trial
was undertaken at 11 clinical sites to evaluate PCA3’s positive
predictive value (PPV, PCA3 score > 60) in the initial biopsy
setting and negative predictive value (NPV, PCA3 score < 20)
in the repeat biopsy setting. PCA3 was obtained prior to biopsy
but following an attentive DRE. We hypothesized that PPV
for an initial prostate biopsy to be at least 55% and that NPV
for a repeat biopsy to be at least 75%.The accuracy of PCA3 in
detecting any prostate cancer and secondarily, high-grade cancer
(Gleason sum > 7), was compared to PCPT risk calculator through
ROC curve analysis.
Results: 880 eligible men (mean age 62 years) were enrolled; 305
had a prior negative prostate biopsy. 99% had an informative
PCA3 test. For the detection of any cancer, PPV was 80% (95% CI:
0.72-0.86) in the initial biopsy group while NPV was 88% (95%
CI: 0.81-0.93) in the repeat biopsy group. PCA3 performance
was superior to PCPT risk estimation in both the initial (upper
figure, p<0.0001) and repeat biopsy setting (lower, p=0.001) and
improved upon the detection of any cancer (p<0.006) and highgrade cancer (p<0.02) when combined with the PCPT risk model.
Conclusions: Independent validation of PCA3 demonstrated
a high PPV in the initial biopsy setting and a high NPV in the
repeat biopsy setting. Given the significant improvements in
risk estimation over PCPT, PCA3 is expected to greatly enhance
clinical decision making.
20
Correlation between biopsy Gleason score on prostate
biopsy and on radical prostatectomy specimen: is there an
improvement since the 2005 International Society of Urological
Pathology Consensus Conference?
D’Hondt F 1, Fonteyne V2, Villeirs G3, De Meerleer G2, Rottey S4, Oosterlinck W 1,
Verbaeys A1, De Groote R1, Van Praet C1, Ost P2, De Visschere PJ3, Praet M5, Lumen N1.
1
Urology, University Hospital, Ghent, Belgium; 2Radiotherapy, University Hospital,
Ghent, Belgium; 3Radiology, University Hospital, Ghent, Belgium; 4Oncology,
University Hospital, Ghent, Belgium; 5Anatomopathology, University Hospital, Ghent,
Belgium
Introduction & Objectives: Histopathology obtained from
prostate biopsy is a key step in the diagnosis of prostate cancer.
The Gleason score is universally accepted as the preferred grading
system for prostate cancer in histopathology obtained from
prostate biopsy as well as from radical prostatectomy (RP). The
biopsy Gleason score (b-GS) is a very important and independent
34
������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������
abstracts
prognostic factor, used in several pre-operative nomograms
and risk group stratifications, finally affecting the therapeutic
decision making. A poor correlation between b-GS and radical
prostatectomy Gleason score (RP-GS) has been reported. The
Gleason grading system underwent its first major revision
in 2005 at an International Society of Urological Pathology
(ISUP) Consensus Conference. Has this revision led to a better
correlation between b-GS and RP-GS since its introduction?
Materials & Methods: This is a retrospective analysis (January
1997-August 2011) of 287 patients in which pathological data
of both prostate biopsy and RP were available. Until 2006, the
original Gleason score was used for grading the prostate biopsy
and the RP specimen. Starting from 2006, the 2005 ISUP Gleason
score was used. Due to this change in scoring system, patients
were divided in two groups: those who underwent RP before 2006
(group 1; n=132) and starting from 2006 (group 2; n=155). The
correlation between the b-GS and RP-GS was evaluated using
Pearson’s correlation coefficient. The difference in correlation
coefficient between group 1 and 2 was evaluated using Fisher’s Z
test. The number of upgrading (higher RP-GS compared to b-GS)
was also calculated and the difference between group 1 and 2 was
evaluated with the χ2-test.
Results: For the whole study population, the correlation
coefficient between b-GS and RP-GS was 0.447. The correlation
coefficient in group 1 and 2 was 0.383 and 0.415 respectively.
The improvement in correlation for group 2 compared to group 1
was not significant (p=0.75). Upgrading of the Gleason score was
observed in 107 out of 287 patients (37.3%). In group 2, there was
significantly less upgrading compared to group 1 (resp. 29 versus
46.9%, p=0.0026).
Conclusions: After introduction of the 2005 ISUP Gleason score,
there was no significant improvement of correlation between
the b-GS and RP-GS. However, upgrading of Gleason score was
significantly reduced after this introduction.
21
Inventory of the PRIAS study criteria for the low-risk prostate
cancer active surveillance
Khalil F, Iken A, Benslimane L, Faik M. Urology A, IBN SINA Hospital, Rabat, Morocco
Introduction: The value of active surveillance in localized
prostate cancer or at low risk of progression as an alternative to
immediate curative treatment has now been demonstrated. The
optimization criteria for selecting patients for this monitoring
is the subject of the study PRIAS (Prostate Cancer Research
International: Active Surveillance). Other studies have followed
and the results are variable. The aim of our study is to make
an inventory of those criteria in order to optimize the patients
selection for better management of this category.
Materials & Methods: In this paper, we compared the results of
the PRIAS study published in 2006 which included 500 patients,
and the results of prospective studies published up to 2011 from
a bibliographic research on the Medline/PubMed database using
the following keywords: PRIAS study, localized prostate cancer,
active surveillance.
Results: After the publication of the PRIAS study in 2006,
4 prospective studies (Klotz, ERSPC, ProtecT, PIVOT) and a
multitude of cohorts (CapSure, SURACAP) were published in the
literature between 2007 and 2011.
Discussion: The inclusion criteria of the PRIAS study were
prostate cancer with a maximum of cT2, a PSA ≤ 10 ng/ml, a
Gleason score ≤ 6 with no more than 2 positive biopsies, and
a doubling time PSA ≤ 0.2 ng/ml/year. Preliminary results of
prospective studies show the feasibility and acceptance of these
criteria by patients. However, details are to be made in terms of
selection criteria and rigor in study’s methodology.
Conclusions: The value of active surveillance as an alternative
to immediate curative treatment has been demonstrated by the
results of the PRIAS study. However, the variability of short-term
results of prospective clinical studies should prompt caution
and not to provide such monitoring as a standard, but rather an
option as part of clinical research protocols.
22
PCA3 surpasses best clinical judgment in selecting men
requiring a repeat prostate biopsy: application of a RAND
decision model to the REDUCE trial placebo cohort
Tombal B1, Andriole GL2, Smets L3, Stoevelaar H3. 1Urology, UCL, Brussels, Belgium;
2
Urology, Barnes-Jewish Hospital, Washington University School of Medicine, St.
Louis, MO, United States; 3Ismar Healthcare NV, Lier, Belgium
Introduction & Objectives: Overall, 10 to 35% of men with
an elevated PSA and a negative initial biopsy (Bx) have prostate
cancer (PCa) on systematic repeat Bx (rBx). Awareness of these
data results in an increasing rate of rBx, with the consequence
of increased risk of both minor and more serious complications
(including septicaemia and hospitalization in 4.1%). Therefore,
there is an urgent need to better individualize the decision for
rBx to reduce the number of rBx while not underdiagnosing
aggressive PCa. We developed a model using the RAND
Appropriateness Method (RAM) to simulate best clinical
judgment and incorporated PCA3 to select patients for rBx.
PCA3 has been shown to predict the probability that a rBx will be
positive and may be indicative of PCa significance.
Methods: We have tested our RAM on a subgroup of the placebo
cohort of the REDUCE study for which PROGENSATM PCA3
Scores were available. These men had a baseline PSA between 2.5
and 10 ng/mL, a prior negative Bx, and planned 2-year and 4-year
rBx. For each scenario (without and with PCA3), the number
of rBx and the number of missed high-grade (Gleason sum ≥ 7)
cancers were assessed.
Results: Data from 1024 subjects were available for analysis.
Using their best clinical judgment (RAM), incorporating PSA,
DRE, number of previous negative Bx, prostate volume and life
expectancy, the expert panel ruled-out 26% of study-mandated
rBx while missing 14 high-grade PCa (Table). PCA3 largely
surpassed best clinical judgment by ruling-out 52% while missing
only 7 high-grade PCa. The most efficient scenario was obtained
by incorporating PCA3 results in the RAM model, leading to a
64% reduction in the number of biopsies while missing only 8
high-grade PCa.
The sensitivity, specificity, PPV and NPV of the RAM model
including PCA3 for Gleason sum ≥ 7 cancer were superior to the
model without PCA3 and the model with PCA3 alone.
Scenario
rBx (n) Reduction
(%)
Missed highgrade PCab (n)
REDUCE
1024
0
a
RAM without PCA3
757
26%
14
PCA3 alone
488
52%
7
RAMa with PCA3
368
64%
8
a: expert recommendations; b: out of 55 Gleason sum ≥ 7 cancers
abstracts ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������� 35
Conclusions: In men with a first negative biopsy, PCA3 alone
or in combination with clinical judgment surpasses best clinical
judgment as a strategy to avoid rBx without compromising
diagnosis of high-grade cancer.
clinically useful information to make more informed repeat
biopsy decisions.
24
23
PROGENSA PCA3 molecular urine assay pivotal U.S. clinical
study confirms utility for predicting repeat biopsy outcome
Groskopf J1, Ward J2, Hertzman B3, Bailen J4, Franco N5, Williams T6, Koziol I7,
Henderson RJ8, Efros M9, Bidair M10, Gittelman M11. 1Gen-Probe Incorporated, San
Diego, CA, United States; 2Urology, MD Anderson Cancer Center, Houston, TX, United
States; 3Tri-State Urological Services, Cincinnati, OH, United States; 4Metropolitan
Urology, Jeffersonville, IN, United States; 5Specialists in Urology, Naples, FL, United
States; 6Florida Urology Specialists, Sarasota, FL, United States; 7 Virginia Urology,
Richmond, VA, United States; 8Regional Urology, Shreveport, Shreveport, LA, United
States; 9AccuMed Research Associates, Garden City, NY, United States; 10San Diego
Clinical Trials, San Diego, CA, United States; 11Urology, South Florida Medical
Research, Aventura, FL, United States
Introduction & Objectives: The PROGENSATM PCA3
molecular urine assay has demonstrated utility to supplement
existing methods for guiding repeat prostate biopsy (rBx)
decisions. In this multi-center prospective pivotal clinical study,
we evaluated its clinical performance in men undergoing rBx.
Materials & Methods: Subjects were enrolled from 14
community-based urology clinics, group health organizations
and academic institutions. The study population consisted of
466 men ≥ 50 years of age who had ≥ 1 prior negative prostate
biopsy and were recommended for rBx. Urine samples were
collected prior to biopsy, and PCA3 Scores determined using the
PROGENSA PCA3 Assay. PCA3 Scores were correlated with rBx
outcome. Multivariable logistic regression (LR) was performed
with factors for PCA3 Score, age, race, serum PSA level, DRE
result, family history and number of previous negative biopsies.
Results: Prostate cancer was diagnosed in 21.9% (102/466) of
subjects. Men with PCA3 Scores < 25 were 4.6 times more likely
to have a negative rBx than men with PCA3 Scores ≥ 25. At this
cutoff, the NPV was 90% (Table); 8 high-grade (Gleason sum
≥ 7) cancers would have been missed whereas 50% of rBx would
have been avoided. The PCA3 Score significantly increased the
predictive accuracy of the LR model: at 90% sensitivity, addition
of the PCA3 Score to the LR model increased specificity by 22.6
(90% CI: 9.0-33.1), PPV by 6.4 (2.8-9.6) and NPV by 7.1 (1.7-13.4)
percentage points relative to the LR model without the PCA3
Score.
Table: Performance characteristics of PCA3 at a cutoff of 25
(95% CI)
Sensitivity
Specificity
NPV
PPV
Odds
ratio
77.5%
57.1%
90.0%
33.6%
4.6
(68.4-84.5)
(52.0-62.1)
(86.593.1)
(30.037.2)
(2.75-7.62)
Evaluation of the PCA3 test in men with PSA between 2.5 and 10
ng/mL undergoing first prostate biopsy
Jelski J1, Speakman M1, Oliver T2, Cuzick J2, Ho L2, Terry B2, Pinney L2, Turner B3, Hines
J4, Green J4, Barua J5, Ahmad A 2, Chinegwundoh F6, Ancheta J7, Lee A5, Akhter W8, Ali
S3, McMeekin F 1, Segaran S1. 1Urology, Musgrove Park Hospital, Taunton, United
Kingdom; 2Queen Mary University London, Wolfson Institute of Preventive Medicine,
London, United Kingdom; 3Urology, Homerton Hospital, London, United Kingdom;
4
Urology, Whipps Cross Hospital, London, United Kingdom; 5Urology, BHR University
Hospitals, Goodmayes, United Kingdom; 6Urology, Newham University Hospital &
Barts and the London NHS Trust, London, United Kingdom; 7Urology, Barts and the
London NHS trust, London, United Kingdom; 8Urology, Newham University Hospital,
London, United Kingdom
Introduction: The value of PSA screening continues to be
questioned due to both the over-diagnosis of indolent cancer and
the number of false positive tests, leading to over-treatment.
European and American studies have shown the clinical utility
of PCA3 in predicting prostate biopsy outcome, but to date there
has been no large study in the UK. Various ‘cut-off’ levels have
been described for PCA3 each with their own merit. A cut-off of
35 provides the best balance between sensitivity and specificity;
however in clinical practice a cut-off of 25 may provide higher
sensitivity so that more cancers are identified. This abstract
reports preliminary results from the evaluation of PCA3 testing
in 6 UK centres in a cohort of men undergoing a first prostate
biopsy.
Patients & Methods: Patients with PSA between 2.5-10 ng/mL,
scheduled for a first prostate biopsy were included from 6 UK
centres. First catch urine samples were collected after digital
rectal examination (3 strokes per lobe) and the PCA3 Score was
determined using the PROGENSATM Assay, blind to outcome
variables, and compared to PSA as a predictor of positive biopsy
at PCA3 cut-offs of 35 and 25.
Results: 317 men have been enrolled; 245 are currently evaluable
and 104 (42%) had cancer on biopsy. PCA3 levels increased with
age (1.92 units/yr, P<0.0001). PCA3 was strongly predictive
of positive biopsy (odds ratio [OR]=2.88 at 35 unit cut-off and
OR=2.21 at 25 unit cut-off), more so than PSA value (AUC=0.687
vs 0.576, P=0.02). Age-specific PCA3 improved predictive power
(OR=3.2 at 35 unit cut-off and OR=2.96 at 25 unit cut-off), but
PCA3 Scores were only slightly higher in men with Gleason grade
7 vs 6 cancers (OR 1.49, ns).
Conclusions: Data confirms that PCA3 testing helps identify
patients likely to have cancer, but these data were not predictive
of Gleason grade. PCA3 can help in counselling patients
whether to perform a first or subsequent biopsy and may help
patient choice in early prostate cancer. Follow up is on-going to
determine the value of PCA3 in predicting outcome particularly
in those on active surveillance.
Conclusions: The clinical utility of the PROGENSA PCA3 Assay
for predicting rBx outcome was confirmed in a multi-center
pivotal U.S. clinical study. Lower PCA3 Scores were associated
with a decreased likelihood of a positive rBx. The NPV was 90%
at a PCA3 Score cutoff of 25; at this cutoff only 8 high-grade
cancers would have been missed whereas 50% of rBx could
have been avoided. LR analysis confirmed that the PCA3 Score
supplements serum PSA and other clinical information for more
accurate prediction of repeat biopsy outcome. The PROGENSA
PCA3 Assay provides clinicians and patients with independent,
36 ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������ abstracts
25
26
Evaluation of the economic burden and impact on patients’
quality of life of metastatic castration resistant prostate
cancer: implementation of an observational study in 6
European countries
How do residents perform on transrectal ultrasound guided
prostate biopsy?
Dass RN1, Hamberg P1, Spencer M1, Wheatley Price P1. 1HEMAR (Health Economics,
Market Access and Reimbursement), Janssen EMEA, Beerse, Belgium; 2Department
of Internal Medicine and Prostate Cancer Center, Sint Franciscus Gasthuis,
Rotterdam, Netherlands
Background: Information on costs related to the management
of metastatic castration resistant prostate cancer (mCRPC) is
limited. The development of robust cost-effectiveness models in
patients with mCRPC requires to collect accurate data on medical
resource use and expenditures, as well as patients’ quality of life
(Qol).
Objectives: To present the design and implementation of a
study, which aimed at evaluating direct and indirect costs,
associated with mCRPC management and Qol at different disease
stages.
Methods: The study was conducted in centres specialised in
prostate cancer treatment in 6 countries: Belgium, France,
Germany, Sweden, Netherlands, and United Kingdom. The study
combined a retrospective chart review with a cross-sectional data
collection at inclusion.
Patients with a confirmed diagnosis of mCRPC and a documented
disease progression were screened from the file system of
participating sites. In Germany, the Association for Interest
Group for Quality Assurance in the Work of Office-based Urooncologists (IQUO) database was also used to identify potential
sites and to screen eligible patients.
Screened patients were invited to participate in the study at the
time of a regular follow-up visit. A total of 900 were expected.
Medical resource use over the previous 2 years (or from diagnosis
of mCRPC onwards if <2 years) were retrospectively collected in
Case Report Forms (CRF) from patients’ medical charts by site
staff or trained external clinical research technicians (CRT).
Direct costs outside of health care, indirect costs (SF-HLQ) and
Qol (FACT-P and EQ-5D) were directly collected from the patient
at the inclusion visit.
Results: Regulatory submissions were initiated in January 2011.
The first patient was included in May 2011. After a 10-month
inclusion period, 47 sites from 6 countries were initiated and
included from 2 to 42 patients. A total of 707 patients were
included: 137 CRT visits were performed, 698 CRF and 687
patient questionnaires were collected.
The main recruitment barrier was the lack of eligible patients
owing to participation in clinical trials within the period of data
collection.
Conclusions: The collection of a robust set of data from various
sources was ensured through a progressive design, which
combined a comprehensive retrospective 2-year chart review
with a “current snapshot” via the completion of a dedicated
questionnaire by the patient.
Ramos R1, Neves T2, Rodrigues T2, Mota R2, Lopes F2, Monteiro H2. 1Urology, Instituto
Português de Oncologia, Lisboa, Portugal; 2Urology, Centro Hospitalar Lisboa
Ocidental, Lisboa, Portugal
Introduction: Transrectal ultrasound guided biopsy remains the
standard for the diagnosis of prostate cancer. Multiple variables
have been suggested to affect cancer positivity rate including core
fragment length and operator. Fragment length is recognized
as a quality parameter. Reports on prostate biopsies performed
by experienced operators have revealed an operator-dependent
variable. The role for a learning curve is not yet clear.
Our aim is to assess prostate biopsy quality when performed by
urology residents, evaluate whether a learning curve exists and
attempt to identify causes for differences between operators.
Methods: Pathological reports from consecutive biopsies
performed during 2011 by three urology residents with specific
training were reviewed. Double sextant biopsies were performed
with side firing probe and under local anesthesia. Repeat
and saturation biopsies were excluded. Relevant patient and
biopsy specimen data were collected. Pathological diagnosis
was classified as cancer, high-grade prostatic intraepithelial
neoplasia, prostatitis and normal. Regression analysis was
used to evaluate whether a learning curve for fragment length
or cancer positivity exists for two of the operators who started
performing biopsies during 2011. SPSS 17.0 was used for
statistical analysis.
Results: Ninety eight first time biopsies performed between
January and December 2011 were included in the final analysis.
Fragment length (mean 11.49 mm) was not significantly different
between operators. Overall prostate cancer detection rate
was 53.1% with statistically different detection rates between
operators (p=0.027). Patient age, PSA, and positive findings on
digital rectal examination and ultrasound were not statistically
different between operators. Fragment core length was not
associated with cancer detection rate nor any other pathological
diagnosis. No learning curve was detected nor did the most
experienced operator have longest fragment core length or cancer
detection rate.
Conclusions: There are significant differences in prostate
cancer detection rates between operators. No learning curve for
fragment length or cancer detection could be identified for the
two younger residents. Causes for differences between operators
performing biopsies on apparently similar patient population
remain an unresolved issue worthy of further investigation.
27
Computer-aided (HistoScanning™) biopsies versus
conventional TRUS-guided prostate biopsies: do targeted
biopsy schemes improve the cancer detection rate?
Hamann MF, Hamann C, Naumann CM, Juenemann KP. Department of Urology and
pediatric Urology, University Hospital of Schleswig -Holstein, Campus Kiel, Kiel,
Germany
Introduction: To define potential improvement in prostate
cancer detection by application of a computer-aided, targeted
biopsy regimen (HistoScanning™).
abstracts ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������� 37
Materials and Methods: We analysed 80 patients who
underwent systematic transrectal, targeted transrectal and
targeted perineal biopsies. Each of them was diagnosed
preoperatively by HistoScanning™, defining a maximum of 3
suspicious areas. These areas were biopsied both transrectally
and via the perineum with a maximum of 3 cores per location.
Results: Overall we detected prostatitis in 30 patients (37.5%),
premalignant lesions in 10 (12.5%) and prostate cancer in 28
(35%) patients of our study group. 78.6% of all cancers were
detected transrectally using 14 cores by systematic biopsy. With a
maximum of 9 targeted cores, 82.1% of all cancers were detected
via the targeted perineal approach. 53.6% were detected using
a maximum of 9 targeted cores via the targeted transrectal
approach.
Conclusions: The presented targeted biopsy scheme achieved
an overall detection rate of 85% of PSA-relevant, pathological
lesions within the prostate. Thus, the presented procedure
shows an improved detection rate in comparison to standard
systematic prostate biopsies, while reducing the number of cores.
Furthermore, the perineal HistoScanning-aided approach seems
to be superior to the transrectal approach with respect to the
prostate cancer detection rate. The presented procedure might be
a step towards reliable ultrasound-based tissue characterisation
and towards fulfilling the requirements of novel therapeutic
strategies.
28
The active surveillance criteria for prostate cancer among
urologists in UK
Hawizy A1, Gujral SJ2, Kelkar A 2, Parker C3. 1Urology, Colchester General Hospital,
Colchester, United Kingdom; 2Urology, King George Hospital, London, United
Kingdom; 3Urology, The Royal Marsden Hospital, London, United Kingdom
Introduction: Active surveillance (AS) is a valid option for
localised prostate cancer (PC) and should be offered to all
patients who are suitable for radical treatment according to NICE
guidelines. However, there is no uniform definition of criteria on
selection and follow-up of these patients in published data. We
carried out an online survey to all BAUS members to review their
criteria on AS in PC.
29
Adoption of a decision algorithm including PCA3 for repeat
prostate biopsy may lead to considerable cost savings in
France
Malavaud B1, Cussenot O2, Mottet N3, Rozet F4, Ruffion A5, Smets L6, Stoevelaar H6.
1
Urology, CHU de Toulouse, Hôpital de Rangueil, Toulouse, France; 2Urology, CHU
Hôpital Tenon (AP-HP), Paris, France; 3Urology, Clinique Mutualiste, St Etienne,
France; 4Urology, Institut Montsouris, Paris, France; 5Urology, Hôpital Henry Gabrielle,
Lyon, France; 6Ismar Healthcare NV, Lier, Belgium
Introduction & Objectives: The PROGENSA PCA3 Score is
predictive of first and repeat prostate biopsy (Bx) outcome. A
recently conducted RAND Appropriateness Method (RAM) study
from 12 European urologists reported that PCA3 Scores were
instrumental in taking appropriate Bx decisions, mainly in men
with ≥ 1 negative prior Bx. In this analysis, the RAM expert
recommendations - without or without consideration of the PCA3
Score - were applied to a modern French cohort of biopsied men
to determine the impact of the PCA3 Score on Bx decisions and
associated costs.
Materials & Methods: The sample consisted of 808 French men
who had Bx in 2010 (78% first, 22% repeat). For these men, the
proportion for which Bx would have been inappropriate (i.e. could
have been avoided) was calculated without and with knowledge
of the PCA3 Score. In addition, we estimated the impact on the
number of Bx and associated costs. Hypotheses for the cost
calculations were 225,000 Bx/year (78% first, 22% repeat),
average cost/Bx 800€, average cost for managing complications/
Bx: ranging from 0€ (scenario 1) to 100€ (scenario 2) to 280€
(scenario 3) and costs PCA3 Score 300€. Scenario 1 is unlikely as
Bx results in hospitalization in 4.1%.
Results: Complete profiles (based on life expectancy, DRE, PSA,
prostate volume, number of prior negative Bx) were available
for 698 men. In the model without PCA3, 2% of all Bx were
considered inappropriate. Knowledge of PCA3 would have
avoided another 7% of Bx. Repeat Bx would have been avoided
in 5% without PCA3 and in 37% with PCA3. This would result
in 18,345 fewer repeat Bx, which would be budget neutral in
scenario 1 and save 5 million € in scenario 3 (Table).
Methods: An online survey was sent to 1200 UK BAUS members
to assess their criteria for selection, follow-up and intervention
of patients who are on AS for PC.
Results: Eleven percent (134/1200) responded and completed
the questionnaire. Regarding PSA limits, 61.2% of the urologists
chose PSA ≤ 10 ng/ml and only 25.5% use PSA density. Gleason
≤ 6 (47.35%), clinical stage ≤ T1c (32.8%), number of positive
cores ≤ 3 (34.4%) are other selection parameters. Only 55.6%
will use core length and 51.5% will perform Magnetic Resonance
Imaging as part of the disease staging while 38.6% do not
perform any imaging. During the follow-up only 18.8% will
review their patients every 3 months and 57.1% do not perform
digital rectal examination. First repeat prostate biopsy is
performed at 12 months by 44% of the urologists and 19% at 18
months. Increased Gleason score and PSA doubling time are the
2 main criteria that would trigger intervention (87.3% and 73%
respectively).
Number of Bx
First
Repeat
Total
Costs: million €
Scenario Scenario Scenario
1*
2*
3*
Current
practice
175,500 49,500
225,000 180.00
202.50
243.00
RAM +
PCA3
175,500 31,155
206,655 180.17
200.84
238.04
Savings
0
(0%)
18,345
(8.2%)
1.66
4.96
18,345
(37%)
-0.17
* Average cost for complications per Bx: scenario 1: 0€, scenario 2: 100€,
scenario 3: 280€
Conclusions: Adoption of RAM expert recommendations
including PCA3 for repeat Bx decisions in clinical practice in
France would reduce the number of repeat Bx and control costs.
Conclusions: There was no uniform or even majority agreement
in most of the criteria used for selection, follow-up and repeat
biopsy for PC patients on AS.
38
������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������
abstracts
30
31
Fractal geometry enables the objective grading of prostate
cancer; Gleason 3+4 ≠ Gleason 4+3!
Safety of abiraterone acetate in patients with castration
resistant prostate carcinoma and concomitant cardiac risk
factors
Waliszewski P1,2, Tanase M3, Abu Eid R4, Klonowski W5, Pierzchalski M5, Stepien P5,
Stepien RA5, Luedecke G6, Wagenlehner F6, Gattenloehner S7, Weidner W6.
1
Department of Urology, Andrology and Pediatric Urology, Justus-Liebig University,
Giessen, Germany; 2Complexity Research Inc. , Poznan, Poland; 3Department of
Computer Sciences, Politehnica University, Bucharest, Romania; 4Georgia Cancer
Research Center, Health Sciences University, Augusta, GA, United States; 5Institute
of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences,
Warsaw, Poland; 6Department of Urology, Andrology and Pediatric Urology, JustusLiebig University, Giessen, Germany; 7Department of Pathology, Justus-Liebig
University, Giessen, Germany
Background: Tumor grading is an important prognostic
criterion for prostate cancer patients. Subjective scoring
according to the Gleason system is influenced by intra- and interobserver variability in up to 80% of cases. There is a need for
objective grading, which would eliminate over- or under-scoring
and enable comparison of results between centers.
Methods : Fractal analysis, based upon self-similarity of
geometric structures, enables characterizing complex patterns
by a numerical value of fractal, i.e. non-integer dimension.
We compared spatial distribution of cell nuclei in prostate
tissues by calculating capacity, information and correlation
dimension based on the Grassberger-Procaccia algorithm as well
as Higuchi dimension. We also constructed a local structural
correlation diagram by a novel Java-based image-transforming
computer algorithm to show how some local blocks of patterns
are correlated and to characterize the cell distribution by
diagram size. Morphometric features of cells were investigated
in 2-dimensional tissue slides after applying the colour
deconvolution algorithm.
Results: Fractal structure was found in all analyzed cases. We
obtained the following values of capacity, information, correlation,
and Higuchi dimension: 1.451 (018), 1.521 (014), 1.986 (004) n=18
for normal prostate; 1.469 (022), 1.530 (017), 1.972 (008) n=15,
1.417 (046) n=22, Gleason 3 pattern; 1.601 (019), 1.648 (015),
1.938 (011) n=18, 1.322 (044) n=32, Gleason 4; and 1.769 (011),
1.766 (010), 1.895 (010) n=10, 1.240 (097) n=2, Gleason 5,
respectively. More random distribution of cell nuclei was
associated with more expanding diagram. The mean values
of the diagram size were 9.5, 30.3, 41.5, 48.6, respectively.
The mean diagram size for Gleason score 3+4 was lower than
for Gleason score 4+3. With regard to the morphometric cell
analysis, sphericity, circularity, and solidity shape were found
to be statistically different between cases with Gleason score 3,
and those with a score of 4 and 5 (p<0.05). Based on the cellular
morphology parameters, discriminant analysis with leave one out
showed that 60% of Gleason score 3 and 4 cases, 63% of Gleason
score 4 and 5 cases and 62% of Gleason score 3 and 5 cases could
be correctly classified.
Conclusions: This approach based upon fractal geometry allows
accurate objective grading of prostate cancer and suggests the
need for incorporating more objective criteria in the grading
system.
Procopio G1, Verzoni E1, de Braud F 1, Salvioni R2, Stagni S2, Villa S3, Bedini N3, Valdagni
R4. 1Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;
2
Urologic Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;
3
Radiation Oncology 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy,
4
Prostate Cancer Program, Radiation Oncology 1, Fondazione IRCCS Istituto
Nazionale dei Tumori, Milan, Italy
Introduction: Abiraterone acetate (AA) is an inhibitor of the
extragonadal androgen biosynthesis that prolongs overall
survival in castration resistant prostate cancer (CRPC) patients
who have received a chemotherapy including docetaxel. The
most common adverse events related to AA therapy were fluid
retention, hypertension, hypokalemia and cardiac disorders. No
safety data are available in patients with concomitant cardiac
disease.
Methods: Metastatic CRPC patients were enrolled in this
prospective study if they were also suffering from a concomitant
controlled cardiovascular disease. AA 1000 mg per day and
prednisone 5 mg bid were administered orally until grade 3-4
adverse events (AE) or disease progression. The primary endpoint
was the safety profile while the secondary endpoints were
progression-free survival and PSA response.
Results: From April to September 2011, 41 CRPC patients with
concomitant cardiovascular disorders have been treated with AA.
Main patients characteristics were: median age 71 years (range 5781 years); baseline mean PSA value 40 ng/ml (range 6.32-995 ng/ml);
the most common sites of disease were bone(27 pts, 81%), lung
(11 pts, 33%) and liver (5 pts, 15%). All patients were previously
challenged with at least 2 lines of hormone therapy and 1
chemotherapy regimen including docetaxel. The most common
pre-existing cardiac disorders were hypertension 22 (66%),
arrhythmias 4 (12%), cardiac ischemia 3 (9%) and conduction
irregularity 2 (4%). Additionally 9 patients (27%) had metabolic
disorders including dislipidemy and hyperglycemia. AA was
feasible without inducing grade 3-4 AE nor treatment
modification. The most common grade 1-2 AE were asthenia
(27%), hypertension (18%) and fluid retention (28%). After a
median time of treatment of 4 months (range 2-7 months) no
dose modifications due to toxicity were required. No efficacy data
are still available.
Conclusions: Treatment with AA was feasible and well tolerated
also in patients suffering from cardiac comorbidities and risk
factors for cardiovascular disease.
32
Radical laparoscopic prostatectomy for locally advanced
disease
Brandenburg JJI, Fossion LMCL. Urology, Maxima medisch Centrum, Veldhoven,
Netherlands
Introduction: Surgical treatment for locally advanced prostate
cancer is still controversial despite recent series in literature. The
EAU guideline also mentions prostatectomy as an option in select
cases.
Methods: Between May 2006 and Febuary 2012 a total of 240
consecutive men underwent endoscopic extraperitoneal radical
abstracts ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������� 39
prostatectomy (EERPE) with or without extended lymph node
dissection depending on clinical staging and nomograms at
our institution. We analysed the data of 75 patients with pT3
prostate cancer regarding the value of preoperative staging,
complications and mid-term oncological follow-up.
Results: Mean age and initial PSA were 66 years (range 54-76)
and 16.6 ng/dl (range 2.1-190). Clinical staging in the overall
group: 80 cT1c, 126 cT2, 34 cT3. In 24 out of 34 cT3 tumours it
involved a true pT3 (29% overstaging). MRI was performed in 45
cases. Sensitivity for lymph node metastases only 11%, specifity
86%. Mean operating time was 231 minutes (120-364), mean
blood loss 596 mililiters (50-2000). Pathological staging in the
overall group: 5 pTx, 149 pT2, 75 pT3, 1 pT4. Positive surgical
margins (PSM) were found in 23 pT3a (52%) and 21 pT3b (68%).
PSM in pT2 were 20%. Lymph node metastases were found in
12 patients: 4 pT3a (9%) and 8 pT3b (25%). Mean lymph node
count was 12 (1-29). A total of 65% of patients experienced no
complications. Most complications were Clavien 1-2, 4% Clavien
3b. Mean follow-up was 27 months (3-61). Non-detectable PSA
levels (<0.1 ng/dl) were found in 46 patients (61%). In case of
pT3a this was 75%, pT3b 41%. In 20 cases there was an indication
for salvage radiotherapy, after which a non-detectable PSA was
reached in 5 patients.
AGE
GROUPS
35-39
40-44
45-49
50-54
55-59
60-64
65-69
70-74
75-79
80-84
85+
Total
1999-2004
NUMBER INCIDENCE
1
0,09
0
0,00
3
0,25
9
0,67
14
1,08
45
2,96
88
4,24
182
6,58
176
5,13
141
3,27
53
2,01
692
26,28
NUMBER
0
1
2
18
56
102
148
229
248
155
63
1022
2005-2010
INCI%
DENCE CHANGE
0,00
N.A
0,08
N.A
0,17
-47
1,34
100
4,34
301,8
6,71
126
7,13
68,1
8,29
25,9
7,23
40,9
4,19
28,1
2,39
18,9
41,87
569,3
*Per 100.000 person-years, age-adjusted using the world standard
Conclusions: Prediction of locally advanced prostate cancer
is difficult with still a lot of overstaging. Postoperative
complications and PSM are comparable to the literature.
Oncological results seem promissing.
33
Prostate cancer epidemiology in a rural area of North Western
Greece
Grivas N, Hastazeris K, Kafarakis V, Tsimaris I, Stavropoulos NE. Urology, General
Hospital Hatzikosta, Ioannina, Greece
Objectives: To collect prostate cancer epidemiology data from
Epirus; a rural area of North Western Greece.
Methods: We reviewed data from 4 hospitals of 4.975 patients
who were submitted to prostate biopsy in Epirus in the 12-year
period 1999 to 2010. Two 6-year periods were compared (19992004 and 2004-2010). All cases of prostate cancer confirmed by
biopsy were recorded and age-standardized incidence rates per
100.000 males were calculated. We also recorded the clinical stage
of prostate cancer and correlated this with PSA and Gleason score.
Results: There were a total of 1.714 new cases of prostate cancer
in Epirus during 1999-2010 and the mean total annual ageadjusted incidence was 34/100.000 men. The mean incidence
during 1999-2004 was 26/100.000 while the mean incidence
during 2005-2010 was 42/100.000 (Table and Figure). The mean
age at diagnosis was 74 years old. The most common Gleason
score was 6. The most common clinical stage was cT2. The median
PSA at diagnosis was 10,83. There was a statistical significant
difference between stage cT4 and all other stages regarding the
PSA value (p=0,000). There was a positive correlation between
Gleason score and PSA (p= 0,013).
Conclusions: There was an almost two-fold increase in incidence
of prostate cancer in this rural area of North Western Greece.
These results are in accordance with the incidence rise recorded in
neighboring countries of South East Europe. However we should
keep in mind the risk of overdiagnosis and the detection of
low-risk cancers that would not have caused morbidity or death
during a man’s lifetime anyway.
Table: Age-adjusted incidence rates* of prostate cancer in Epirus,
1999-2004 and 2005-2010
40
34
The initial management of prostate cancer in France in 2010:
results of a retrospective chart review of 808 men having
prostate biopsy
Malavaud B1, Bordier B1, Cussenot O2, Meesen B3, Mottet N4, Rozet F5, Ruffion A6,
Stoevelaar H3. 1Urology, CHU de Toulouse, Hôpital de Rangeuil, Toulouse, France;
2
Urology, CHU Hôpital Tenon (AP-HP), Paris, France; 3Ismar Healthcare NV, Lier,
Belgium; 4Urology, Clinique Mutualiste, St Etienne, France; 5Urology, Institut
Montsouris, Paris, France; 6Urology, Hôpital Henry Gabrielle, Lyon, France
Introduction & Objectives: In clinical practice it is often
uncertain which men need a (repeat) prostate biopsy (Bx) and
which men with prostate cancer (PCa) are suitable for active
surveillance (AS) as guidelines are often not straightforward at
the patient-specific level. There is also limited information on
which men eventually have a Bx and on initial treatment choice.
We aimed to make an inventory of the characteristics and initial
treatment choice of men who underwent Bx in clinical practice in
France.
Materials & Methods: This was a French multi-centre,
retrospective chart review study including men who underwent
Bx in 2010. Data on clinical variables were collected using an
electronic data capture system. To avoid selection bias inclusion of
patient cases took the order of ‘most recent case to less recent case’.
Results: 808 men were included. 632 men (78%) had an initial
Bx and 176 men (22%) ≥ 1 repeat Bx (Table). The mean age was 64
years and the mean (median) PSA was 11.6 (7.0) ng/mL. 23% of
men were ≥ 70 years, 25% had a PSA > 10 ng/mL and 28% had a
suspicious DRE (Table). 52% of men had a positive initial Bx and
26% a positive repeat Bx. In men with a positive biopsy a mean
of 12 cores (range 1-42) was performed. 111 patients (34%) had
low-risk PCa (NCCN classification: stage T1c-2a, PSA < 10 ng/mL
and Gleason sum < 7), 195 (59%) were at intermediate/high risk
of disease progression and in 7% this information was missing.
29% of patients had clinical stage ≥ T2b, 61% had > 20% of
������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������
abstracts
positive cores and 52% had a Gleason sum ≥ 7. The most common
treatment was radical therapy (radical prostatectomy or radiation
therapy) in 54% of patients. Of those at low risk, 38% received AS
and 40% radical therapy.
Table: Distribution of clinical variables (n=808)
shown that HPV is frequently detected in prostate lesions and
prostate cancer. HPV E7 monoclonal antibody should be further
studied to understand if it could be useful together with ki67,
to better define low grade non-aggressive tumours and the
prognosis of prostate cancer. This first report showed that nuclear
and cytoplasmic E7 positivity have different meanings. The first
one is associated to low nuclear degree and the second one to
highly replicative recurrent tumours.
Variable
Value
Percentage
Age (years)
< 70
≥ 70
77
23
Life expectancy (years)
≥ 10
< 10
90
10
36
DRE
Normal
Suspicious
Unknown/not reported
59
28
13
Computer-aided ultrasonography-guided biopsy: accurate tool
in prostate cancer detection
Previous biopsies
Not performed
1 negative biopsy
≥ 2 negative biopsies
78
14
8
De Coninck V 1, Braeckman J1, Autier P2, Michielsen D1. 1Urology, UZ Brussel, Jette,
Belgium; 2Epidemiology, International Agency for Research on Cancer, Lyon, France
Prostate volume (cc)
< 30
30-60
> 60
14
66
20
Objectives: To evaluate the efficiency of computer-aided
ultrasonography-guided biopsy for prostate cancer detection in
men at high risk.
PSA (ng/mL)
<3
3-10
> 10
3
72
25
Methods: During a 6-months period, 41 men were referred
for prostate biopsy under computer-aided ultrasonographic
guidance. This imaging technique has been developed to detect
or exclude prostate cancer with high accuracy. Men were selected
on DRE suspicious for prostate cancer, PSA > 4.0 ng/mL or PSA
velocity > 0.75 ng/mL/year, and suspicious computer-aided
ultrasonographic examination. The number of random biopsy
cores varied depending upon the prostate volume. Targeted
biopsies were taken in case of computer-aided ultrasonographic
area suspicious for malignancy. Directed biopsies were
performed by extrapolating suspicious foci on computeraided ultrasonography to transrectal ultrasound images. The
Pearson’s chi-squared test was used to determine the statistical
significance for the comparison of data.
Conclusions: The French sample of men biopsied in clinical
practice in 2010 was at a relatively high risk of having PCa.
Radical therapy was the most common treatment choice. In men
with low-risk PCa, radical therapy and AS were used most often
and to the same extent.
35
HPV E7 monoclonal antibody may help to define better
prognosis of prostate cancer
Stanta G1, Barbazza R1, Roggero E2, Marchesin F 1, Pracella D1, Bonin S1. 1Medical
Sciences, University of Trieste - Cattinara Hospital, Trieste, Italy; 2Oncology Institute
of Southern Switzerland (IOSI), Bellinzona, Switzerland
Introduction: There is a lot of confusion about the persistence
of HPV infection in the prostate. A new commercial monoclonal
antibody against E7 can give us the chance to study prostate
tumours by searching if this antibody can be useful in diagnosis
and in predicting better prognosis.
Methods: In 39 surgical cases of prostate cancer with 10 years
of follow-up, we have tested a new monoclonal antibody that can
recognize HPV E7 protein. Its specificity was detected in prostate
lesions at the IHC level with the pre-absorption of the antigen.
After the DNA extraction HPV-L1 gene was detected, confirming
the virus persisting genome. The positivity was compared with
clinical, follow-up data and ki67 positivity.
Results: We have found a positivity for HPV E7 in 63% of
prostate cancer cases and this positivity was both nuclear and
cytoplasmic with any kind of possible association. We divided
the cases according to the usual clinical parameters that showed
how prostate capsule infiltration, Gleason grading and nuclear
grading were related to recurrences. Recently it has been put
into evidence that ki67 is the best marker of prognosis available
for prostate carcinoma. We confirm this hypothesis because all
the cases with a ki67 positivity over 10% recurred. We compared
all this clinical and pathological data with the nuclear and
cytoplasmic positivity for HPV E7. We observed that nuclear
positivity was mostly associated to low nuclear degree (G1)
tumours and that cytoplasmic positivity was related to high ki67
positivity.
Conclusions: This first study of HPV E7 detection, in a limited
number of cases of prostate cancer with long follow-up, has
Results: Prostate cancer was found in 17 of 41 men (41%). In
patients with cancer, computer-aided ultrasonography-guided
biopsy was 4.5-fold more likely to detect cancer than random
biopsy. Prostate cancer detection rate for random biopsy and
directed biopsy was 13% and 58%, respectively. Computer-aided
ultrasonography-guided biopsy significantly decreased the
number of biopsy necessary (p-value < 0.0001).
Conclusions: We conclude that computer-aided ultrasonography
can be used to direct biopsies in specific regions of the prostate
with a high cancer detection rate.
37
Near-total gland ablation of locally confined low- and
intermediate-risk prostate cancer using Magnetic Resonance
Guided Focused Ultrasound Surgery (MRgFUS)
Desai S, Patil A, Raina S. Radiology, Jaslok Hospital and Research Centre, Mumbai,
India
Introduction: In May 2010, the Jaslok Hospital and Research
Centre, Mumbai, India has installed an ExAblate Magnetic
Resonance Guided Focused Ultrasound Surgery (MRgFUS) multiapplication platform (InSightec, Tirat Carmel, Israel) in the 1.5T
GE (General Electric) MRI suite.
The MRgFUS platform includes also an investigational ExAblate
2100 Device for Prostate which comprises an endorectal focused
ultrasound transducer. Like in other applications, the HDTX
MRI provides high resolution anatomical visualization for
accurate definition of desired treatment margins, and real-time
abstracts ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������� 41
temperature monitoring allowing case-dependent adjustment
and customization of the therapeutic dose during treatment, for
maximal safety and effectiveness.
Locally confined prostate cancer is frequently an indolent disease
which is currently being frequently overtreated by various radical
treatment modalities involving a significant complication rate
and long-lasting morbidity. Due to the severity of therapeutic
adverse events and morbidity from one hand and the frequent
relatively low risk for disease progression, many patients are
reluctant to undergo definitive treatments and instead they
remain under active surveillance. However, active surveillance
involves significant psychological and financial burden, as well
as some risk for undetected cancer progression. Thus, focal or
near-total gland ablation may offer to patients with low- and
intermediate-risk prostate cancer a middle ground solution
in which, the prostate tissue suspected to bear cancerous foci
is ablated, while functional structures like rectum, urethral
sphincters, bladder wall, and potentially the neurovascular
bundles, are preserved.
Up to date, 5 near-total gland ablation MRgFUS treatments were
performed in our hospital for low- and intermediate-risk prostate
cancer patients, with proven locally confined disease.
Materials & Methods: Treatments were performed in the
Jaslok Hospital and Research Centre as part of an industrialsponsored, IRB-approved prospective single-arm phase I trial.
In the study were included patients aged 50 years or older with
low-risk or intermediate-risk organ-confined prostate cancer,
diagnosed by 12-core TRUS-guided endorectal biopsy; up to
Gleason score of 7=3+4 (not 4+3 and no 5 scores); PSA <15 ng/
dl and no contraindications to MRI; maximum prostate gland
volume was not greater than 40 cc. Patients should also be
eligible for epidural or general anesthesia and willing and able to
give consent and attend all study visits as defined in the protocol.
Patients with prostatic calcifications near the rectal wall, or with
any previous therapeutic anal, rectal, or prostatic interventions,
as well as patients with contraindications for anesthesia, were
excluded.
The primary endpoints of the protocol are treatment safety and
initial effectiveness in terms of disease-free survival measured
by post-treatment stable PSA nadir levels and negative biopsy
results.
Pre-treatment evaluation included medical history, physical
examination, PSA level, CT scan, multifunctional MRI, and
TRUS-guided prostate biopsies of 12 cores. The patient’s
urological and sexual baseline functional status was assessed,
using the Expanded Prostate Cancer Index Composite
questionnaire (EPIC-AUASI-SF12, 2002).
Treatments were conducted after a minimum duration of 6 weeks
post-biopsy. Treatments were performed in the MR suite using
the ExAblate 2100 Prostate system and the GE 1.5T HDXT MRI.
Patients underwent pre-treatment bowel preparation to avoid
fecal residue in the rectum during treatment. Treatments were
performed under epidural anesthesia with conscious sedation,
and with a suprapubic catheter constantly draining the bladder.
Post-treatment follow-up includes, 1 week, and 1, 3 6, 9, 12, 18
and 24 months visits; periodic PSA levels measurements; posttherapeutic function assessments using the EPIC-AUASI-SF12
questionnaire; multifunctional MRI scans at 6 and 24 months of
follow-up and repeated prostate biopsies at 24 months of followup or earlier, based on PSA rise.
Preliminary initial results: By now we treated under this study
protocol 5 patients with low- and intermediate-risk prostate cancer.
All the patients were in the age group 50 to 85 yrs. All prostate
volumes were less than 40 cc and PSA levels were between 5 to 15
ng/ml before treatment. Cancerous foci were invisible on
screening multifunctional MRI scans in all 5 patients.
Neurovascular bundles were bilaterally preserved in the
treatment of the 2 young patients, unilaterally preserved in
treatment of 1 patient. These patients reported pre-treatment
good erectile function.
Due to movements that occurred during treatment, the
treatment of 1 of the elderly patients was interrupted before
completion of ablating the prostate base. Due to the patient’s
age the urologist deferred the decision regarding completing the
treatment in a second session, to follow-up PSA results.
No adverse events occurred during or after treatments.
Since the urethra was included in these treatments, patients
remained with the suprapubic catheter until they were able to
urinate spontaneously without residual urinary volume seen on
ultrasound examination.
In all the patients the suprapubic catheters were removed
between 3 to 5 weeks. No incontinence was reported.
At 6 weeks of follow-up, PSA levels dropped from baseline of 5 to
15 ng/ml to 1 to 3.8 ng/ml in all the 5 patients.
Conclusions: Near-total gland ablation using Magnetic
Resonance Guided Focused Ultrasound seems like a potentially
safe minimally-invasive therapeutic alternative for young potent
or elderly patients with low- and intermediate-risk prostate
cancer, for whom surgery, cryoablation or radiotherapy might
be aggressive and mutilating, however more data need to be
obtained.
Abstracts accepted for poster
presentation
38
Pooled analysis of two protocols of intermittent hormonal
therapy in advanced prostate cancer
Brausi M1, Gonçalves F2, Kliment J3, Queimadelos M4, Calais da Silva FE5, Robertson
C6. 1Urology, S.Agostino Institute, Modena, Italy; 2Urology, Klinika LFUH, Bratislava,
Slovakia; 3Urology, Jessenius school of Medicine, Martin, Slovakia; 4Urology,
Policlinica LaRosaleda, S.Compostela, Spain; 5Urology, H.Desterro, Lisbon, Portugal;
6
Statistics, University of Strathclyde, Edibourg, United Kingdom
Background & Objectives: Few randomized studies have
compared intermittent hormonal therapy with continuous
therapy for the treatment of advanced prostate cancer. We
present pooled results from two randomized trials, with similar
protocols and identical data collection. The objective is to
compare overall and cause specific survival in patients receiving
intermittent therapy compared to those receiving continuous
therapy.
Materials & Methods: In MAB 626 patients (aged 50-88,
mean=73) were randomized; 314 to continuous therapy and
312 to intermittent therapy. In CAB 917 patients (aged 44-91,
mean=72) have been randomized; 462 to intermittent therapy
and 455 to continuous. The statistical analysis was through a
pooled individual level meta analysis with interaction tests to
assess the constancy of treatment comparisons across studies.
Cox proportional hazard models are used to investigate the effect
42 ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������ abstracts
of treatment (intermittent therapy compared to continuous)
on time from randomization until death. In a prognostic factor
analysis the effects of age, T category, metastatic status, Gleason
score and PSA at randomization are investigated. Interaction
tests are used to assess if the effects of these prognostic factors
are the same in the two studies.
MAB patients received cyproterone acetate (CPA) 200 mg for 2
weeks and then monthly depot injections of a LhRH analogue
plus 200 mg of CPA daily during induction. Patients randomized
to the intermittent arm ceased treatment while those
randomized to the continuous arm received 200 mg of CPA daily
plus a LhRH analogue. Patients randomized to the intermittent,
received when on treatment 300 mg CPA and the continuous arm
the same reduction treatment.
Results: The median time on study for patients in the MAB trial
was 57 months and for the CAB study 54 months. There are a
total of 4213 person years at risk on CAB; these are equally split
between the two treatments arms, 3514 years for continuous
and 3586 for intermittent. There are differences between the two
studies in terms of the patients recruited. In MAB there are more
older patients, more T4, more M1, more G3, more Gleason 8+, and
more with higher PSA at randomization. PSA at randomization
was a design issue and to be randomized on CAB, PSA had to be
less than 4 ng/ml. A total of 474 patients are known to have died
in the MAB study and 421 in the CAB study.
Overall survival
There is no evidence that the effect of intermittent therapy on
overall survival was different in the two studies, p=0,25 and
pooling the data is appropriate. Survival in the CAB study is
better than in the MAB, p<0,0001 with a hazard ratio (HR) of
0,64 (95% CI 0,56 to 0,72). This can probably be explained by
a better selection of patients for inclusion in CAB – lower PSA
and less metastatic. There are no differences in overall survival,
adjusting for study as the death rate in CAB is lower than in
MAB, p=0,077 with HR 0,98 (95% CI 0,86 to 1,12).
Cause specific survival
In MAB 51% of deaths were due to cancer and 28% due to CVD,
with 21% other causes, while in CAB 36% of deaths were cancer
deaths and 46% CVD and 19% other causes. In both studies there
are fewer CVD deaths in the intermittent arm, HR 0,87 (95% CI
0,70 to 1,09), p=0,22. While in MAB, in particular, there are more
cancer deaths in the intermittent arm, HR 1,29 (95% CI 0,00 to
1,65), p=0,054 but not in CAB, HR 0,98 (95% CI 0,71 to 1,34),
p=0,90. Overall the hazard of death from other causes was lower
in the intermittent arm HR 0,83 (95% CI 0,62 to 1,12), p=0,23.
There is no statistical evidence of differential effects in the two
studies with regard to CVD (p=0,58) and cancer deaths (p=0,16)
and other causes (p=0,33).
Prognostic factor
Metastatic status, high Gleason score, older age and higher PSA
are all associated with poorer survival. There is no evidence that
the effects of the prognostic factors varied over the two studies
p=0,53. Adjusting for these the HR of death from any cause in
CAB is 0,81 (95% CI 0,70 to 0,94), p<0,01. This is still significant
so these prognostic factors do not explain all the differences in
survival between MAB and CAB. Adjusting for the prognostic
factors there is still no evidence of any difference between
intermittent and continuous therapy with a HR of 0,99 (95% CI
0,87 to 1,14), p=0,99.
Conclusions: Intermittent therapy should be considered for
use in routine practice since it is associated with no reduction
in survival, no clinically meaningful impairment in quality of
life, better sexual activity and considerable economic benefit to
individual and community.
39
Rectal toxicity 7 years after high-dose radiation for prostate
cancer: clinical and dosimetric predictors
Rancati T 1, Fellin G2, Fiorino C3, Vavassori V4, Cagna E5, Mauro FA6, Gabriele P7,
Valdagni R8. 1Prostate Cancer Program, Fondazione IRCCS Istituto Nazionale dei
Tumori, Milan, Italy; 2Radiation Oncology, Ospedale Santa Chiara, Trento, Italy;
3
Medical Physics, Istituto Scientifico San Raffaele, Milan, Italy; 4Radiation Oncology,
Humanitas - Gavazzeni, Bergamo, Italy; 5Radiation Oncology, Ospedale Sant’Anna,
Como, Italy; 6Radiation Oncology, Ospedale Villa Maria Cecilia, Lugo di Romagna,
Italy; 7Radiation Oncology, Institute for Cancer Research and Treatment, Candiolo,
Italy; 8Prostate Cancer Program and Radiation Oncology 1, Fondazione IRCCS Istituto
Nazionale dei Tumori, Milan, Italy
Purpose: To evaluate long-term prevalence of late rectal
bleeding (lrb) and of late fecal incontinence (linc) after high-dose
radiotherapy (RT) in prostate cancer patients (pts) accrued in a
prospective trial (RT doses: 70-80Gy,1.8-2Gy/fr) and to model
the relationship between lrb/linc and clinical/dosimetric factors.
Materials & Methods: Self-reported questionnaires (qs) of
515 pts with a minimum follow up of 6 yrs (median 7 yrs) were
analyzed with respect to lbr and linc.
Correlation between pre-treatment morbidities, hormonal
therapy, drug prescription, presence of diabetes or hypertension,
abdominal surgery prior to RT, presence of acute toxicity, pelvic
nodes and seminal vesicles irradiation, mean rectal dose, dosevolume histograms constraints (from V20Gy to V75Gy) and lrb/
linc was investigated by logistic analyses.
347/515 pts had at least 3 toxicity (tox) qs in the first 3 yrs after
the end of RT. Correlation between the mean score of linc in the
first 3 yrs and linc at 7 yrs was also investigated.
Results: 32 G1, 2 G2 and 3 G3 lrb were registered. 50 G1, 3 G2
and 3 G3 linc were reported.
Lrb was only correlated to V75Gy (continuous variable, p=0.02,
OR=1.07).
The prevalence of lrb ≥1 at 7 yrs was significantly correlated with
the incidence of G2-G3 lrb in the first 3 yrs after RT treatment:
42% in pts with G2-G3 lrb in the first 3 yrs vs 6% in non-lrb pts
(p<0.0001).
Linc was correlated to multiple variables. In multivariable
analysis (overall p<0.0001, AUC=0.77) V40Gy (continuous
variable, p=0.09, OR=1.015), use of antihypertensives (protective
factors, p=0.005, OR=0.38), presence of abdominal surgery
before RT (p=0.004, OR=4.7), presence of haemorrhoids
(p=0.008, OR=2.6) and presence of G2-G3 acute incontinence
(p=0.007, OR=4.4) resulted to be correlated to linc.
Linc at 7 yrs was also correlated to the mean incontinence scores
in the first 3 yrs (p<0.0001): pts without linc at 7 yrs had a mean
score of 0.1 during the first 3 yrs, while pts with G1 and with G2G3 linc at 7 yrs had a mean score of 0.5 and 0.78 during the first 3
yrs, respectively.
Conclusions: A fraction of pts is still experiencing rectal tox
symptoms 7 yrs after RT: 7% lrb and 11% linc. Prevalence of tox
at 7 yrs is significantly correlated to incidence in the first 3 yrs
after RT, this is an indication of a chronicization of symptoms,
with linc playing the major role.
Mean score for incontinence during the first 36 mos after RT can
be used as a surrogate endpoint for >6 yrs linc.
abstracts ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������� 43
40
Histopathological characteristics and post mortem PSA values
of elderly Greek males with non cancerous prostates. The
preliminary results of an autopsy study
Stamatiou K 1, Pierris N1, Skolarikos A 2. 1Urology, Tzaneio Hospital, Pireas, Greece;
2
Urology, Sismanogleio Hospital, Athens, Greece
Introduction: The introduction and common use of serum PSA
(Prostate Specific Antigen) has been demonstrated a useful index
for prostate cancer diagnosis but in the same time has increased
the number of unnecessary prostate biopsies. In fact, PSA
levels alone do not provide enough information to distinguish
between benign prostate conditions and cancer. Age-specific
reference ranges have been proposed to increase the specificity
and positive predictive value of PSA testing for detecting early
prostate cancer and thus to decrease the number of unnecessary
prostate biopsies. Since benign prostatic hyperplasia (BPH) is a
very common condition, the mean normal PSA per age group in
a certain population should be dependent on the incidence and
degree of BPH. Moreover, since significant differences in mean
PSA by race were found, age-specific PSA values as described by
Oesterling et al., are probably not suitable for all populations.
Aim: The aim of the study is to investigate the histopathological
characteristics of non cancerous prostates of elderly Greek males
and to correlate them with post mortem PSA values.
Materials & Methods: Data were obtained from 120 autopsy
specimens of the prostate gland and sera of men aged above 60
and under 98 years of age, born and living in Greece, who died
(between 8/2010 and 4/2011) of causes other than carcinoma of
the prostate. Cases found with macroscopic foci of carcinoma,
cases suspected of a history of prostate cancer and putrefacted
cadavers were excluded from the study.
The whole prostate and seminal vesicles were removed with
accuracy. The specimens were weighted, and examined
macroscopically. The surface of the 2 lobes was colored in
different colors and fixed in acetic acid. A 10% solution of
formalin was injected uniformly per cm3 into the gland and the
specimen was then immersed in formalin solution allowed to
fix for 3 days. Base and apex were also removed by transversal
sections and the slices were cut at 4 mm intervals. Specimens
were divided and step-sectioned at 4 mm intervals perpendicular
to the long axis of the gland. Pieces were post fixed, re-sectioned,
dehydrated, cleared in xylene, embedded in paraffin, and stained
with haematoxilin–eosin stain. The microscopy slides were
numbered, registered and examined by an expert pathologist.
Results: Histological BPH was the more common lesion of the
prostate gland among our study population, however, medium
prostates (25-50 cc) were more frequent than large prostates
(>50 cc). More than half of the examined prostates had evidence
of histological non specific prostatitis. Prostate atrophy was rare
however was by far more frequent in the prostates of elderly men
(age groups 80-89 and >90). The mean post mortem PSA value for
the age group 70-79 was 3.324, the mean post mortem PSA value
for the age group 80-89 was 3.73 and the mean post mortem PSA
value for the age group >90 was 2.88.
Conclusions: Our reduced sample does not stand any statistic
analysis, but these observations highlight the fact that a given
PSA value may have a different clinical meaning for patients of
different races and nations. This is of outmost importance given
that screening rates for prostate cancer by serum PSA testing
appear to be higher in men older than 70 years and especially
for the southern European countries where people enjoy one
of the highest life expectancies worldwide. To our knowledge,
44
currently tPSA cut-off values have not been determined for each
ethnic group and thus large randomised studies are needed in
order to determine the appropriate PSA values to decide upon the
necessity for prostate biopsy.
41
For preoperatively potent men, low free testosterone (FT)
is a significant predictor of potency return versus total
testosterone (TT) levels in robot-assisted radical prostatectomy
(RARP)
Ahlering T, Osann K, Chang A, Morales B, Skarecky D. Urology, University of California
Medical Center, Orange, CA, United States
Purpose: We examined testosterone (T) and FT levels following
RARP to see if lowered levels correlated with postoperative
recovery of sexual function.
Methods: Prospective data was entered for men undergoing
RARP by a single surgeon. Recent postoperative T levels
(N=154) and SHBG were used to calculate FT (N=204). The
study group included potent men of all ages (40-78 years) only
with preoperative IIEF-5 scores of 22-25. Postoperative potency
was defined as 2 affirmative answers to “erections adequate
for penetration” and “were the erections satisfactory” using
self administered validated questionnaires. Men with FT ≤5.1
(LowFT, N=43) were compared to men with FT ≥5.1 (NormalFT,
N=161) and to men with TT.
Results: Table 1 presents pertinent pre and postoperative
findings. Patient group characteristics were very similar except
for men with LowFT and TT <300 which were significantly older.
The NormalFT group had a minimum 2-fold increased rate of
recovery across the 2 year followup, p ≤.02. TT <300 and >300
were not significant in predicting potency return throughout 24
M, all p =NS.
Conclusions: Interestingly we did not find that TT <300 or
LowFT predicted lower baseline characteristics. Men with LowFT
in distinction to TT <300 levels had statistically diminished
return of potency. This data suggests that independently of
patient characteristics and surgical technique, LowFT likely
contributes postoperative impotence a minimum 2 fold.
TABLE 1
N
Age
Preoperative
PSA
AUA
Bother
IIEF-5
BMI
Prostate
weight
Postoperative
PDE-5 qD*
(Mos.)
Ave follow-up
TT
Potent 3 M
9M
15 M
24 M
LowFT NormalFT pvalue
26
91
63.5
58.5
≤.01
TT
<300
51
61.4
TT
>300
103
58.7
pvalue
5.8
8.4
1.5
23.8
27.3
53.2
5.1
8.1
1.4
24.2
27.0
52.2
.35
.97
.96
.11
.81
.78
5.8
7.6
1.4
23.9
27.9
52.9
5.8
8.1
1.4
24.1
26.9
51.2
.95
.63
.77
.32
.39
.56
7.8
7.1
.65
6.9
8.0
.46
26.7
254
(4%)
(17%)
(18%)
(33%)
22.9
400
(24%)
(46%)
(55%)
(73%)
.33
≤.01
.024
.015
.003
.003
25.7
231
(11%)
(27%)
(27%)
(47%)
22.6
453
(22%)
(41%)
(45%)
(61%)
.30
≤.01
.10
.13
.07
.21
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.02
abstracts
42
Incorporation and economic impact of robotic surgery within a
community hospital and healthcare system
Laungani RG. Urology, Piedmont Hospital, Atlanta, GA, United States
Introduction & Objectives: Healthcare in the US is a topic of
major debate and has come under relentless scrutiny as of recent.
Robotic surgery, due to its decreased morbidity, may have a major
cost saving impact to both hospitals and healthcare systems.
Community hospitals have shown the largest growth in regard
to purchase of robotic systems but have realized the pitfalls
of robotic surgery including the expense related to purchase,
maintenance, and training of physicians. We discovered
important points for incorporation of robotic surgery within a
community hospital which translate into a significant reduction
in costs for the hospital system as well as decreased charges for
the healthcare system.
Methods: A retrospective review of radical prostatectomy cases
from 2004 to 2009 was conducted. This represented the time
period before and after the adoption of robotics into the hospital
system. Data related to hospital costs, charges per case, patient
hospital stay and number of cases was reviewed.
Results: With the introduction of robotics into the hospital
system in 2006 we noticed an initial increase in cost and charges
per case; $16,495 for open radical prostatectomy vs $25,593 for
robotic prostatectomy. Cost and charges significantly decreased
after 2 years and continued to decrease to below that for open
radical prostatectomy; $14,481 for robotic prostatectomy in
2009. Average savings per case was $2911 with mean annual
savings of $262,000. Case volume significantly increased
from 39 open radical prostatectomies in 2004 to 269 robotic
prostatectomies in 2009. Patient length of stay (days) decreased
significantly from 2.72 to 1.08. This equates to 460 patient days
saved for robotic radical prostatectomy compared to open radical
prostatectomy. Urologists who are fellowship trained in robotics
translate into a large case volume experience with no separate
training or learning curve required. Increased case volume
resulted in decreased costs and charges per patient after a period
of 2 years compared to that of open radical prostatectomy.
rebuilding to reverse the preprostatectomy anatomical structure.
In this study, we retrospectively analyzed the affecting factors for
the postoperative urinary continence recovery after RARP.
Materials & Methods: This study included consecutive 100
patients with prostate cancer treated with bilateral nerve-sparing
radical prostatectomy between 2008 and 2011. All patients had
preoperative functional and oncological data available, including
age at surgery, body mass index, prostate specific antigen, and
erectile and urinary function. Also, operative data consisted of
nerve-sparing status, estimated blood loss (EBL), and operative
duration. Median operative time and EBL were 191 minutes and
200 mL, respectively. Out of 100, nerve-sparing procedure was
applied in 64 (64.0%) for unilateral and 20 (20.0%) for bilateral.
Urinary continence was defined as wearing less than one pad, just
for safety. Univariate and multivariate Cox regression models
were applied to test the association between factors and urinary
continence recovery after surgery.
Results: At a mean postoperative followup of 12.5 months
(range 3 to 32) 97 patients (97.0%) had recovered urinary
continence. Overall urinary continence recovery rate at 1, 3,
6 and 12 month post RARP was 50.0, 83.0, 94.0, and 98.0%,
respectively. On univariate analysis patient age and the nervesparing status were significantly associated with urinary
continence recovery, p=0.048 and p=0.020, respectively.
On multivariate Cox regression analysis, the nerve-sparing
procedure, including unilateral and bilateral, was demonstrated
to be the only independent predictor of urinary continence
recovery after RARP.
Conclusions: Nerve-sparing procedure might affect the pelvic
vascular as well as synthetic nerve function, which may affect the
condition of external urinary sphincter, leading to early urinary
continence recovery.
Conclusions: In the US, a large percentage of robotic growth
has occurred in the community hospital setting. Investment in a
robotic surgical system can be a daunting and expensive task for
a community hospital, but we have found that over a period of 1-2
years benefits can extend to a community hospital and healthcare
system in the form of overall decreased costs, decreased charges,
more efficient care and excellent patient outcomes.
44
43
Detection, localization and exclusion of high grade prostate
cancer with multiparametric MRI: correlation with radical
prostatectomy histopathology
Nerve-sparing impacts on early recovery of postoperative
urinary continence in patients treated with total urinary
reconstruction on robot-assisted radical prostatectomy
Shiroki R , Maruyama T , Kusaka M , Fukami N , Fukaya K , Ishise H , Sasaki H ,
Hoshinaga K 2. 1Urology, Fujita Health University School of Medicine, Nagoya, Aichi,
Japan; 2Urology, Fujita Health University, Nagoya, Aichi, Japan
1
2
2
2
2
2
2
Introduction & Objectives: The association between surgical
procedure and urinary continence recovery after robot-assisted
radical prostatectomy (RARP) remains controversial. Our RARP
procedure consisted of ultradissection of bladder neck without
opening the endopelvic fascia and total urinary reconstruction,
comprising posterior (Rocco stitch), anterior, and lateral
De Visschere PJ1, De Potter A 2, Villeirs G1. 1Radiology, Ghent University Hospital,
Ghent, Belgium; 2Pathology, Ghent University Hospital, Ghent, Belgium
Purpose: To determine the value of multiparametric MRI
(mpMRI) for the detection, localization and exclusion of high
grade prostate cancer (Gleason 4+3 or higher) in patients with
elevated serum PSA.
Materials & Methods: 29 patients (mean age 62 years, range
52-71) with mean PSA of 12.2 ng/ml (range 4.8-36.0 ng/ml)
underwent mpMRI followed by radical prostatectomy (within
mean 54 days, range 2-194 days). mpMRI was performed on a
abstracts ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������� 45
1.5T scanner with endorectal coil and included T2-weighted
imaging, diffusion-weighted imaging and spectroscopic imaging.
The peripheral zone was divided into 18 segments, and MRI
findings were correlated to whole mount histopathology.
Results: In total 522 segments were histopathologically
evaluated. No tumor was found in 356 segments, low grade
prostate cancer (Gleason 3+4 or lower) in 130 segments and high
grade prostate cancer (Gleason 4+3 or higher) in 36 segments.
Sensitivity, specificity and accuracy of mpMRI for the detection
and localization of segments with high grade prostate cancer
were 77.8%, 84.6% and 84.1% respectively. The negative
predictive value for excluding high grade cancer was 98.1%.
Conclusions: mpMRI in a subset of patients with elevated
PSA with radical prostatectomy correlation (i.e. excluding nonsurgical indications) allows detection and localization of high
grade prostate cancer, but has a higher value in the exclusion of
high grade prostate cancer.
45
Hemi-salvage HIFU in patients with radiorecurrent prostate
cancer
Baco E1, Crouzet S2, Rud E3, Rouviere O4, Chapelon JY5, Berge V 1, Gelet A6. 1Urology,
Oslo University Hospital, Aker, Oslo, Norway; 2Hospices Civils de Lyon, Urology and
Transplantation3, E. Herriot Hospital, Lyon, France; 3Radiology, Oslo University
Hospital, Aker, Oslo, Norway; 4Radiology, Hospices Civils de Lyon, E. Herriot Hospital,
Lyon, France; 5INSERM, Lab. TAU Inserm, Unit 1032, Université de Lyon4, Lyon, France;
6
Hospices Civils de Lyon, Urology and Transplantation3, E. Herriot Hospital, Lyon,
FranceLyon, France
Introduction: One third of patients treated with external
beam radiation therapy (EBRT) for localized prostate cancer
(PCa) experience local recurrence. Salvage treatment options
include prostatectomy, cryoablation, and high intensity focused
ultrasound (HIFU). Whole gland treatment in these patients
offers acceptable cancer control, but carries a risk of severe
urinary incontinence and reduction of QoL. In patients with
unilateral local relapse, focal HIFU is feasible. The aim of this
prospective study was to evaluate the effect of Hemi HIFU in
patients with unilateral recurrence after EBRT.
Materials & Methods: Between 2009 and 2011, 43 patients
were prospectively included in 2 centers. Inclusion criteria were
positive MRI and biopsy in 1 lobe diagnosing unilateral cancer
after EBRT (41 pts) and after brachytherapy (2 pts). Median
age was 69 years (51-78), pre-HIFU PSA was 5.19 ng/mL (3.476.91) and Gleason score was 7 (≤7: 28, ≥8: 10, ND 7). Mean
follow-up was 12 months. HIFU treatment was performed with
Ablatherm®.
Results: The mean PSA nadir was 0.77 (0.51-1.04). Control
biopsies (in 12 pts with rising PSA) were negative in 75%
(n=9) and positive in 25% (n=3): in the treated lobe: 2, in the
contralateral lobe: 1.
Disease progression ocurred in 10 pts (23%): local recurrence:
3 pts, metastasis: 4 pts and rising PSA without local recurrence
or proven metastasis in 3 pts. Five patients received androgen
deprivation and 1 redo-HIFU.
Severe incontinence occurred in 7% (n=3). The mean ICS score
before/after treatment were score A: 0.51±0.27 / 2.30±0.59 and
score B: 0.37±0.18 / 1.9±0.46. No significant change of EORTC-C
30 QoL and IPSS scores were observed: QLC30 35.07±8.57 VS
34.56±9.98; IPSS: 7.07±5.77 VS 8.84±5.72. The IIEF5 score
decreased from 11.89±8.64 to 7.66±6.62.
46
Conclusions: Hemi-salvage HIFU is efficient in patients with
unilateral radio-recurrent PCa with a preserved Qol. It may offer
comparable cancer control to whole gland treatment.
46
The choice of active surveillance from the patients’ perspective
Bellardita L1, Magnani T 1, Marenghi C1, Catania S1, Rancati T 1, Salvioni R2, Valdagni R3.
1
Prostate Cancer Program, Fondazione IRCCS Istituto Nazionale dei Tumori Milano,
Milano, Italy; 2Urology, Fondazione IRCCS Istituto Nazionale dei Tumori Milano,
Milano, Italy; 3Prostate Cancer Program, Radiation Oncology 1, Fondazione IRCCS
Istituto Nazionale dei Tumori Milano, Milano, Italy
Introduction: Active surveillance (AS) for the management
of low risk prostate cancer is benefiting from an emerging
consensus from medical professionals. It is still debated whether
the choice of such an option could be positively accepted by
patients given the emotional burden brought about by the word
“cancer”. The aim of this study is to report patients’ motivations
and perceived advantages/disadvantages when electing AS.
Methods: Between September 2007 and March 2012,
167 patients enrolled in AS were administered self-report
questionnaires, including a structured interview aimed to collect
patients’ personal history, and to investigate the reasons for
choosing AS. We report here results related to the following
questions: 1. Why did you choose AS? (Patients could select more
than one option) 2. Is there anyone who influenced your choice?
If yes, who? 3. What are the advantages of AS? 4. What are the
disadvantages of AS?
Results: Patients’ mean age was 67. Patients answered to
question 1 as follows: a) I trusted what the physicians told
me 75%, b) I trust this Cancer Center 62%, c) I am comforted
and satisfied by participating in a protocol 25%, d) I trusted
what other people told me 10%, e) To avoid side effects of the
therapies and maintain my quality of life 66%, f) I do not trust
active therapies 3%, g) I found scientific papers about AS 14%,
h) Medical checks are frequent 33%, i) It is a reversible option
48%. Influence on the choice of AS (question 2) was reported
as follows: a) General practitioner 2%, b) Cancer Center 22%, c)
Family 4%, d) Other physicians 18%, e) Other 10%. On the other
hand, 44% of the patients reported that no one had influenced
their choice. Advantages of choosing AS were reported as:
frequent checks 24%, avoiding surgery 41%, avoiding side effects
of the therapies 18%, maintaining QoL 9%, reversibility of choice
6%, clinical research 2%. Disadvantages of choosing AS were:
frequent checks 4%, recurrence of biopsy 3%, anxiety 12%, fear
for disease progression 22%, distance from Cancer Center 2%,
none 57%. Only one patient reported medical checks as scarce
and thus as a disadvantage.
Conclusions: Patients in our study cohort emphasized the
importance of trust toward clinicians that proposed AS alongside
self-motivation. One of the implications for clinical practice of
these data is the emphasis that should be given to doctor-patient
relationship given the complex decision making and uncertainty
underlying AS.
������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������
abstracts
47
48
Predictors of upgrading/upsizing after 1-year re-biopsy in men
participating in a prospective active surveillance program
Transperineal sector biopsies: their role in active surveillance
Nicolai N1, Alvisi MF2, Rancati T2, Colecchia M3, Salvioni R1, Villa S4, Bedini N , Biasoni
D1, Marenghi C2, Avuzzi B 4, Paolini B3, Magnani T2, Catania S2, Valdagni R2,4. 1Urology,
Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; 2Prostate Cancer
Program, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;
3
Anatomopathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;
4
Radiation Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
Introduction: Since 2005, we have been proposing active
surveillance (AS) in selected low-risk prostate cancer (PCa) pts.
AS protocols include repeat biopsy at pre-defined follow-up
intervals. We here consider the outcome of the first re-biopsy (1
yr after AS beginning) and analyse its possible correlation with
diagnosis variables.
Methods: Age, iPSA, PSA density, number of positive cores, %
of positive cores, max and average core length containing cancer,
number of negative cores at diagnosis, total number of cores
at diagnosis, total number of cores at 1-yr re-biopsy, prostate
volume, DRE were considered as factors potentially influencing
upgrading (UPG)/upsizing (UPS). GPS was not considered (all pts
had GPS=3+3).
Three separate endpoints were considered: (1) UPS OR UPG; (2)
UPG and (3) UPS.
Multivariable logistic regression (MVLR) was used to analyse
correlations between variables and endpoints at first re-biopsy.
Results: Statistical analysis was performed on 255 pts with
complete records (1 yr min follow-up).
40% of pts had a negative 1-yr biopsy (0 positive cores), 45 pts
had UPS/UPG after re-biopsy, switching to radical treatment.
MVLR resulted in a 2-variable model for endpoint “UPS OR UPG”
(p=0.02, AUC=0.63): number of negative cores >5 (OR=0.43,
p=0.19) and prostate volume >60cc (OR=0.27, p=0.04).
When UPG (27 pts) was considered separately a 3-variable model
was determined (p=0.018, AUC=0.71): age >60yrs (OR=3.4,
p=0.12), PSA density (continuous variable, OR=1.04, p=0.16) and
prostate volume >60cc (OR=0.17, p=0.1).
Taking UPS (18 pts) as the endpoint, MLVR resulted in a
5-variable model (p=0.03, AUC=0.73) including: DRE (T2a vs
T1c, OR=3.03, p=0.16), number of negative cores >5 (OR=0.32,
p=0.30), total number of cores at 1-yr re-biopsy (discrete variable,
OR=1.14, p=0.18), age >60yrs (OR=0.48, p=0.23) and max core
length containing cancer >10% (OR=3.4, p=0.03).
Conclusions: UPS is strongly related to “volume” variables, and,
as a consequence, may be strongly affected by sampling. UPG
is more related to PSA density. It is noteworthy as age has an
opposite effect on the two endpoints (protective for UPS and risk
factor for UPG) and that max core length containing cancer is
highly predictive of UPS.
Such analysis may generate the hypothesis that two different
populations of PCa pts are subjected to drop-off from AS
protocols. Biological and clinical implications deserve further
studies.
Supported by Fond Monzino
Chang RTM, Popert R, Vyas L, Kinsella J, Challacombe B, Cahill D. Urology, Guy’s
Hospital, London, United Kingdom
Introduction & Objectives: Many men with low risk
prostate cancer on transrectal biopsy appear suitable for
active surveillance (AS). Under staging and grading at
diagnosis can result in delayed treatment and risk of poorer
oncological outcomes. In most AS series about 30% men
have active treatment at a median of 2 years for presumed
disease progression/choice but this may represent disease
mischaracterised at initial biopsy. So it is essential to accurately
stratify patients before surveillance. We have routinely offered
transperineal sector prostate biopsies (TPSB), using 24-32 cores,
to all patients considering AS.
Materials & Methods: 350 patients with apparent low to
intermediate risk prostate cancer after transrectal prostate
biopsy (TRUS Bx) underwent TPSB.
Results: Median age 64 yrs (38-84). Median PSA 7.2 ug/l (0.1458). 190 had Gleason 3+3, 115 had Gleason 3+4 and 45 >3+4
disease. 145 (41%) patients elected for definitive treatment,
in 112 because there was an upgrade or higher disease volume
compared with the original TRUS Bx. 33 patients chose definitive
treatment rather than continued AS. 205 (59%) patients entered
our AS programme, in 25 follow up data is incomplete leaving 180
for analysis. 61 have had repeat TPSB within our protocol and at a
median follow up at 2 years in 56/61 (92%) the Gleason score and
volume of disease was unchanged. Only 5/180, 2.8%, have had
treatment for disease progression and additionally 4/180 (2.2%)
have chosen active intervention over continued surveillance,
despite no evidence of progression.
Conclusions: TRUS biopsies under-estimate Gleason grade or
cancer volume compared with TPSB. In our cohort of AS patients
only 2.8%, at a median follow up of 2 years, have transferred to
definitive treatment for disease progression. TPSB provides the
best method to exclude higher risk disease from AS programmes.
49
Impact of body mass index on the operative course and
complications of robot assisted laparoscopic prostatectomy
(RALP)
Rambaran SS1, Kliffen M2, van den Ouden D1, de Lange DCD1, Engel RP1, Klaver OS1.
1
Urology, Maasstad ziekenhuis, Rotterdam, Netherlands; 2Pathology, Maasstad
ziekenhuis, Rotterdam, Netherlands
Objectives: To determine if obesity is associated with prolonged
surgery or more complications during and after surgery and
different oncological and functional outcomes in patients
undergoing RALP.
Patients & Methods: We evaluated 425 patients who underwent
RALP between January 2009 and March 2011, performed in our
hospital by the same surgical team. Patients had a mean BMI
of 26,7 kg/m2 (15,5 - 42). Patients were categorized as normal
weight (BMI <25 kg/m2, n=81), overweight (BMI 25 - 29,9 kg/
m2, n=254) and obese (BMI ≥30 kg/m2, n=90). Intraoperative
parameters evaluated were console time and estimated blood
loss. Postoperative parameters evaluated were pathological
T-stadium, positive surgical margin status (PSM), postoperative
Gleason score, biochemical recurrence (BCR), prostate volume,
postoperative complications, length of hospital stay, continence
abstracts ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������� 47
rate and potency rate. PSA progression (PSA ≥0.2) was used as
a surrogate endpoint of progression. Functional outcome was
measured using the ICIQ and the use of pads and the SHIM. Only
preoperative potent patients who underwent bilateral nerve
sparing were included in the analysis of potency outcomes.
Results: Overweight and obese patients had longer mean
operative times (132 and 144,7 vs. 122,3 min, resp; p<0,01).
Mean estimated blood loss was not significant between groups
(320,4 and 392 vs. 259 cc, resp; p=0,871). Overweight and obese
patients were not significantly associated with an increased
pathological T-stage (T2a 15,4%, T2a 16,7% vs. T2a 17,3%; T2c
54,3%, T2c 62,2% vs. T2c 49,4%; T3a 16,1%, T3a 10% vs. T3a
19,8%; T3b 12,6%, T3b 11,1% vs. T3b 12,3%, resp; p=0,0847),
PSM (54/254 (21,3%), 21/90 (23,3%) vs. 18/81 (22,2%), resp;
p=0,376), postoperative Gleason score (p=0,946), BCR (43/243
(17,7%), 18/103 (17,5%) vs. 8/79 (10,1%), resp; p=0,264),
prostate volume (54,1 and 62,2 vs. 49,3 g, resp; p=0,204) and
postoperative complications (17/254 (7%), 8/90 (8,9%) vs.
8/81 patients (9,9%), resp; p=0,10) compared to normal weight
patients. Length of hospital stay was significantly longer
in overweight and obese patients (3,5 and 3,8 vs. 3,3 days,
resp; p<0,01) compared to normal weight patients. Return of
continence at 1 year was not significantly different between
groups; 38/41 (92,7%), 115/119 (96,6%) vs. 23/26 (88,5%) resp;
p=0.384. Potency rate was significantly better in the normal
weight group, compared to the overweight and obese patients;
15/21 (71,4%), 17/30 (56,7%) and 5/10 (50%) resp; p<0,01.
Conclusions: RALP is a safe and effective procedure regardless
of BMI. There is a slight increase in operative time and length
of hospital stay compared to patients with normal weight,
whereas pathological T-stage, PSM, postoperative Gleason score,
BCR, complications rates, estimated blood loss and return of
continence were not significantly different. Normal weight
patients have a better potency rate compared to overweight and
obese patients. Further long-term follow up with more patients is
required to verify this initial observation.
50
Pathologic findings in patients undergoing radical
prostatectomy in candidates for active surveillance
Calleja-Escudero J, Calvo-Gonzalez R, Valsero-Herguedas E, Pascual-Fernandez A,
Bedate-Nuñez M, Pesquera-Ortega L, Cortiñas-González JR. Urology, University Clinic
Hospital, Valladolid, Spain
Objectives: The number of patients with prostate cancer and low
tumor burden has led to consider active surveillance as an option
for treatment. This strategy aims to reduce the overtreatment,
although the selection of these patients is challenging. We
analyzed the clinical and pathological findings of radical
prostatectomies performed in patient candidates for active
surveillance according to NCCN criteria.
Methods: Between 2004 and 2011 we performed 324 radical
prostatectomies from which 36 (11%) met the NCCN criteria for
active surveillance, which are PSA <10 ng/ml, T1c, PSA density
<0.15 ng/ml/g, Gleason score ≤6 and <3 positive prostate biopsy
cores and ≤50% cancer in each core. We analyzed the correlation
of histological data.
Results: The mean age was 62 years and the mean PSA was 5.45
ng/ml. 21 patients had a previous biopsy and 18 affected a single
core. Radical prostatectomy Gleason score was 7 in 19 (52.7%)
patients and in 1 no tumor was found. In 24 cases (66.6%) the
tumor involvement was greater than in the biopsy in terms of
bilateral.
48
Conclusions: A significant percentage of patients eligible for
active surveillance showed a pathological aggressive profile. The
selection of eligible patients should be careful while awaiting
the results of clinical trials and new diagnostic tools that enable
better understanding of tumor aggressiveness.
51
Extended pelvic lymph node dissection can enhance survival in
prostate cancer patients with minimal lymph node invasion
Alekseev BY, Nyushko KM, Andrianov AN, Vorobyev NV. Urology, Moscow Hertzen
Oncology Institute, Moscow, Russian Federation
Aim & Objectives: To assess biochemical recurrent-free survival
(RFS) in intermediate and high risk prostate cancer (PC) patients
after radical prostatectomy (RPE) with extended pelvic lymph
node dissection (E-PLND) in subject to number of lymph node
(LN) metastases revealed.
Materials & Methods: Retrospective analysis of a database
from 595 patients after RPE and PLND since 2006 till 2011 in
our institution was performed. 262 consecutive PC patients
with intermediate and high risk, who had undergone RPE with
E-PLND, were included in the study. Patients with extensive LN
metastases who received adjuvant hormonal treatment were
excluded from the analysis. Mean patient’s age was 67.8±6.47
(46-77) years; mean PSA level 14.8±10.7 (1.5-79.0) ng/ml. Mean
number of LN removed was 24.96±7.6 (15-52). Morphological
stage pT2a-T2c was verified in 146 (55.7%) patients, pT3a-T4
– in 116 (44.3%). pN0 was found in 199 (76.0%); 1 or 2 LN
metastases were found in 34 (12.9%); > 2 – in 29 (11.1%) patients.
Morphological Gleason score 2-4 was in 3 (1.1%) patients, 5-6 – in
129 (49.2%), 7 – in 100 (38.2%), 8-10 – in 24 (9.2%) patients. In 6
(2.3%) patients Gleason score was not assessed. Median follow-up
(FU) time was 21.4±15.4 (6-73) months.
Results: During FU period recurrences were observed in 74
(28.2%) patients. Recurrences were diagnosed in 33 (16.6%), 17
(50%) and 24 (82.6%) patients with pN0, with 1-2 LN metastases
and with > 2 metastases respectively (p<0.05). Cumulative
2-year RFS was 85.4±3%; 44.96±10.7% and 22.6±8.5% in groups
respectively (p<0.0001). Morphological stage, Gleason score
and PSA level correlated with probability of PSA relapse after
operation (p<0.0001).
Conclusions: RFS significantly differed in groups of patients
with no metastases, 1-2 metastases and > 2 metastases revealed.
2-year RFS rate in patients with 1-2 LN metastases was 45%,
thus this patients could be candidates for delayed hormonal
treatment.
52
Prostate-specific antigen nadir and time to prostatespecific antigen nadir following maximal androgen blockade
independently predict the prognosis in patients with metastatic
prostate cancer
Kim SJ, Hong SY, Cho DS, Kim S, Ahn HS. Urology, Ajou University School of Medicine,
Suwon, Republic of Korea
Objectives: The aim of this study was to evaluate the influence
of prostate-specific antigen (PSA) kinetics following maximal
androgen blockade (MAB) on the disease progression and cancerspecific survival in patients with metastatic, hormone sensitive
prostate cancer.
������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������
abstracts
Methods: One hundred thirty-one patients with metastatic,
hormone sensitive prostate cancer treated with MAB (combination
of LHRH agonists or bilateral orchiectomy and antiandrogen)
at our institution were included in this study. The median age of
the patients at MAB initiation was 72 years (range, 49-92 years).
Patients’ characteristics, PSA at MAB initiation, PSA nadir, TTN
(time to PSA nadir), and PSA decline were analyzed by using
univariate and multivariate analysis.
Results: With a median follow-up of 30 months (range, 7-133
months), 97 patients (74.0%) showed disease progression and
65 patients (49.6%) died. Prostate cancer-specific deaths were
59 cases (45.0%). On univariate analysis, PSA at MAB initiation,
PSA nadir, TTN, and PSA decline were significant predictors
of progression-free survival. And PSA nadir, TTN, and PSA
decline were significant predictors of cancer-specific survival.
On multivariate analysis, higher PSA nadir (≥0.2 ng/ml) and
shorter TTN (<8 months) were independent predictors of shorter
progression-free and cancer-specific survivals. In the combined
analysis of PSA nadir and TTN, patients with higher PSA nadir and
shorter TTN had the worst progression-free survival (hazard ratio
14.098, p<0.001) and cancer-specific survival (hazard ratio 14.050,
p<0.001) compared to those with lower PSA nadir and longer TTN.
Conclusions: Our results suggest that the higher PSA nadir level
and shorter TTN following MAB are associated with the higher
risk of disease progression and poor survival in patients with
metastatic, hormone sensitive prostate cancer. Furthermore, these
two variables have synergistic effect on the outcome.
negative margins (61% vs 90% at 5 years, p<0.0005). Higher
Gleason score was also significantly associated with shorter time
to BCR (2-year BCRFS = 97% for Gleason ≤ 6, 81% for Gleason
7, and 43% for Gleason ≥ 8, p<0.0005). In multivariate analysis,
pathologic stage, positive margin status, and Gleason score were
independently associated with time to BCR after adjusting for
age and pre-operative PSA. Hazard ratios (HRs) were 3.3 (95% CI:
1.7 - 6.4) and 4.8 (95% CI: 2.3 - 10.0) for stage 3A and 3B relative
to stage 2. HRs with increasing Gleason score were 4.1 (95% CI:
1.7 - 10.3) for Gleason 7 and 11.4 (95% CI: 4.3 - 30.3) for Gleason
≥ 8 relative to Gleason ≤ 6. PSM was associated with a smaller
increase in HR of 1.7 (95% CI: 1.1 - 2.9) after adjusting for all
other factors.
Conclusions: Our data demonstrate the independent role
of stage, PSM and Gleason score for biochemical recurrence.
Gleason score ≥ 8 is the strongest predictor for biochemical
recurrence. Pathologic stage 3 and Gleason 7 were also associated
with a 3- to 4-fold increased risk for BCR. PSM contributed an
additional small increase in risk for BCR after adjusting for other
factors.
TABLE 1
Hazard
ratio*
Lower 95%
CI
Upper 95%
CI
Pathological stage
pT2
1.0
pT3A
3.3
1.7
6.4
pT3B
4.8
2.3
10.0
Gleason score
53
Predictors for biochemical recurrence in robot assisted radical
prostatectomy
Ahlering T, Lusch A, Osann K, Liss M, Skarecky D. Urology, University of California
Irvine, Orange, CA, United States
Objectives: Positive surgical margins (PSM) in men undergoing
radical prostatectomy are an independent predictor for
biochemical recurrence (BCR). We analyzed the incidence,
associated factors and time to BCR of patients with prostate
cancer and PSM in our first 435 robotic assisted radical
prostatectomies.
Materials & Methods: The study cohort consisted of 435
consecutive patients undergoing RARP between June 2002 and
August 2006. All surgeries were performed by a single surgeon
(TA). Pre-operative PSA, positive margin status, pathological
Gleason grade, pathological stage were identified. Three patients
were lost to follow-up and 4 others (2 pT0 and 2 pT4) were
excluded from analyses. Results included 428 patients with
pathological stage 2 (n=311), 3A (n=92) or 3B (n=25). No patient
had secondary therapy until documented BCR. BCR was defined
as a serum prostate specific antigen level ≥ 0.2ng/ml with a
confirmatory value or the date of any treatment intervention:
hormonal, radiation or chemotherapy. BCR-free survival
(BCRFS) was investigated using Kaplan-Meier methods and Cox
Proportional Hazards Regression.
Results: The mean age ± standard deviation (SD) was 61.4 years
± 7.1. Sixty-seven patients (16%) experienced a BCR. Median
time to recurrence was 18 months (range 0.5 months - 8.2 years).
Median follow-up for those who did not have a BCR was 5.4 years
(range 1 month - 9.1 years). 272 (63%) had ≥ 5 years follow-up;
391 (91%) had ≥ 2 years follow-up, 4 patients (1%) were lost to
follow-up post surgery. BCRFS at 5 years was 94% for stage 2,
64% for stage 3A and 51% for stage 3B (log rank test, p<0.0005).
Patients with PSM had lower BCRFS compared to those with
≤6
1.0
=7
4.1
1.7
10.3
≥8
11.4
4.3
30.3
1.1
2.9
Surgical margin
Negative
1.0
Positive
1.7
54
Survival, Continence and Potency (SCP) outcomes 5-years after
robot-assisted radical prostatectomy
Ficarra V, Suardi N, Borghesi M, Bardelli I, De Naeyer G, Schatteman P, Carpentier P,
Mottrie A. Urology, O.L.V. Robotic Surgery Institute and Urologic Clinic, Aalst, Belgium
Objectives: To evaluate the oncological and functional outcomes
5-years after robot-assisted radical prostatectomy (RARP) using
the new system Survival, Continence and Potency (SCP).
Materials: Between 2003 and 2005, 184 consecutive patients
with OC PCa received a RARP in our department. All patients
were evaluated after a minimum follow-up of 5-year. Biochemical
disease-free survival, continence and potency results were
classified according to SCP system recently proposed in literature
by Ficarra et al. In details, the S category is subdivided into three
different groups: (1) patients treated with adjuvant therapies
(Sx), (2) patients without PSA recurrence (S0), and (3) patients
with PSA > 0.2 ng/ml (S1). The C category is subdivided into
(1) patients not using a pad (C0), (2) patients using one pad for
security (C1), and (3) patients using > 1 pad (C2). Cx category is
used for patients who were not evaluable because of preoperative
incontinence. P category is subdivided into (1) patients not
evaluable (Px), (2) patients potent (SHIM > 17) without any aids
(P0), and (3) patients potent (SHIM > 17) with erectile aids (P1)
or patients impotent (SHIM < 17) (P2).
abstracts ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������� 49
Results:
All cases
(185 pts)
Sx= 24 (13%)
S0= 143 (78%)
S1= 16 (9%)
Cx= 0
C0= 146
(79.2%)
C1= 20 (10.9%)
C2= 17 (9.3%)
Excluded
Sx – Cx – Px
(94 cases)
S0= 88
(93.6%)
S1= 6 (6.4%)
Px Patients
Sx
Excluded Sx
Patients
(65 cases)
(24 cases)
S0= 55 (84.6%)
S1= 10 (15.4%)
C0= 82
(87.2%)
C1= 8 (8.5%)
C2= 4 (4.3%)
C0= 45 (70%)
C1= 10 (15%)
C2= 10 (15%)
Px= 73 (39.9%) P0= 48 (51%)
P0= 52 (28.4%) P1= 34 (36%)
P1= 41 (22.9%) P2= 12 (13%)
P2= 17 (9.3%)
Our results suggest that BV and PS measurements, reflect
angiogenesis and that perfusion CT with 64-row scanner is a
feasible technique for assessing prostate cancer vascularization.
C0= 19 (79%)
C1= 2 (8%)
C2= 3 (13%)
Px= 8 (33%)
P0= 4 (17%)
P1= 7 (29%)
P2= 5 (21%)
Conclusions: Our series shows the longest available follow-up in
patients treated with RARP. Oncological and functional outcomes
are very good also after a follow-up longer than 5 years.
55
Prostate cancer angiogenesis: a preliminary experience with
64-row multidetector CT (MDCT) perfusion - do quantitative
measurements distinguish tumor?
Pastore AL, Palleschi G, Petrozza V, Di Cristofano C, Rengo M, Osimani M, Laghi A,
Carbone A. Sapienza University of Rome, Faculty of Pharmacy and Medicine,
Department of medico-surgical Sciences and Biotechnologies, Urology Unit, Latina, Italy
Aim: To prospectively test the relationships between
quantitative CT perfusion parameters and immunohistochemical
microvascular density (MVD), considered as a gold standard
marker of angiogenesis, in prostate cancer.
Materials & Methods: The used study protocol conformed to
the guidelines of the Declaration of Helsinki and each patient
provided written consent in accordance with the requirements
of our institutional review board. Between July 2009 and April
2010, twenty-one consecutive men (mean age, 59.7 years; age
range, 48-71 years) were enrolled. All patients were examined
with 64-row MDCT scanner for dynamic CT perfusion imaging,
before prostatectomy surgery. Perfusion data sets were analyzed
by the software (Prostate protocol, Perfusion 4.0). Values for
each of the four perfusion CT parameters (blood volume (BV),
blood flow (BF), mean transit time (MTT), permeability surfacearea product measurements (PS)) were recorded and correlated
with MVD and mean vascular area (MVA) calculated from
macrosection-correspondent areas.
Results: ANOVA analysis revealed more noticeable significant
differences in BV, MTT and PS perfusion parameters (P<0.01).
Two-tailed Spearman rank correlation analysis showed highest
correlation level between BV and PS measurements of prostate
cancer squares (respectively 0,618 and 0,614), while MTT was
inversely correlated (-0,475). BV and PS showed highest area
under the curve (AUC) value in ROC analysis (0,769 and 0,708).
Discussion & Conclusions: This complex study design was
fitted to investigate if CT was also a feasible technique in prostate
cancer, and how CT perfusion parameters changed on the basis of
vascularization of malignant or benign prostate lesions. Results
were encouraging and, above all, statistically significant. In
particular, we found there were significant differences in mean
values of BV, MTT and PS parameters between benign lesions and
malignant lesions as confirmed by other authors.
56
High-intensity focused ultrasonography for treatment of
localized prostate cancer: a mid-term follow-up
Siegel FP1, Ferber A 2, Egner T2, Schoen G2, Trojan L1, Schiefelbein F2, Heinrich E1.
1
Urology, UMM (University Medical Centre Mannheim), Mannheim, Germany; 2Urology,
Missionsaerztliche Klinik, Wuerzburg, Germany
Objectives: To report on the mid-term functional and
oncological outcomes, from 1 institution, of high-intensity
focused ultrasound (HIFU) in the treatment of localized prostate
cancer.
Patients & Methods: A total of 151 patients with histology
proven localized prostate cancer have been treated using the
Ablatherm device. The mean follow-up including 96 patients
was 36.4 months (range 12 to 55). Mean age was 73.8 years
(range 51 to 89). According to D’Amico risk stratification 53.1%
had a low, 37.5% an intermediate and 9.4% a high risk prostatic
carcinoma. Biochemical failure was defined according to the
Phoenix definition (PSA nadir + 2 ng/ml). Follow-up included
PSA measurement, IPSS, DRE, post voiding residual urine,
maximum urinary flow rate, TRUS and transrectal biopsy in case
of biochemical failure or suspicious digital rectal examination.
Results: The median PSA nadir after HIFU therapy was 0.63
ng/ml (range 0 to 9.94). Median PSA at follow-up examination
was 0.84 ng/ml. Biochemical failure was recognized in 23.9%
of patients (low risk: 15.6%, intermediate risk: 31%, high risk
44.4%). Sextant biopsies in case of biochemical failure revealed
39.1% local recurrence. 34.8% developed metastatic disease
and 26.1% of PSA elevations were without detectable reason.
Intraoperative no major complications were noted. Three
patients developed epididymitis and further 3 patients had mild
abdominal pain after cystostomy removement. 15.8% underwent
transurethral resection after HIFU because of bladder outlet
obstruction. Two (2.1%) patients developed relapsing bladder
neck sclerosis. Mean IPSS improved significantly from 10.25 to
8.6 (p=0.02). Six percent of patients reported stress incontinence
using 1 pad during daytime, but no severe stress incontinence
(grade 2 to 3) was observed. Better or unchanged quality of life
was indicated by 77%.
Conclusions: Our results confirm efficacy and low invasiveness
of HIFU in the treatment of localized prostate cancer. Patients
with low risk carcinomas are likely to be most suitable for
efficient HIFU treatment.
50 ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������ abstracts
57
Treatment of primary tumor in patients with metastatic
prostate cancer: an unanswered question
Taylor D1, Collette L2, Berthold D1. 1Medical Oncology, CHUV, Lausanne, Switzerland;
2
Statistics, EORTC, Brussels, Belgium
Aim: Treatment of metastatic prostate cancer at diagnosis
is androgen deprivation therapy (ADT). In that scenario, the
treatment of the primary tumor in the absence of local symptoms is
unnecessary as the main therapeutic goal is to temporarily control
incurable disease with minimal toxicity.
Several trials have shown that increasing local control with
combined radiotherapy (RT) and ADT in locally advanced prostate
cancer has a favorable impact on survival. Our hypothesis is that
the treatment of the primary tumor is important for the control
of distant metastasis and therefore could improve outcome also in
metastatic patients.
Methods: EORTC 22863 randomized study investigated the role
of 3-year ADT combined with external pelvic RT vs. RT alone for
locally advanced prostate cancer. Its data was recomputed in order
to determine events according to time. The type of first recurrence,
locoregional, distant or both were analysed.
Results: With a median follow-up of 10 years, in the group of
patients treated with RT alone (n=208), 26 (12.5%) had as a first
event a locoregional recurrence, 63 (30.3%) had distant recurrence
and 14 (6.7%) experienced both. In the group treated with RT
followed by 3 years of hormonal therapy (n=207), 9 (4.3%) had
locoregional recurrence, 34 (16.4%) had distant recurrence and 1
(0.5%) had recurrence in both sites. Distant recurrence was in both
groups the most important site for relapse.
Interpretation: This data shows that androgen suppression
reduces both local and distant recurrences when added to RT in
locally advanced prostate cancer. We hypothesize that 3 years of
ADT may not eradicate distant micro-metastatic lesions and thus
cannot fully account for long-term disease control. We suggest that
increased local control and therefore irradiation of the primary
tumor could reduce the occurrence of macro-metastatic disease
and therefore be beneficial on outcome. Factors from the primary
tumor could induce a stimulus to dormant micro-metastasis and
hence contribute to the development of distant lesions and poor
outcome. This hypothesis can only be confirmed or rejected in a
randomized trial for men with newly diagnosed metastatic prostate
cancer.
58
Correlation between the biopsy gleason and radical
prostatectomy specimen
Calleja-Escudero J, Calvo-Gonzalez R, Valsero-Herguedas E, Pascual-Fernandez A,
Bedate-Nuñez M, Pesquera-Ortega L, Cortiñas-González JR. Urology, University Clinic
Hospital, Valladolid, Spain
Objectives: The Gleason score in prostate biopsy cores is
important in decision making for prostate cancer. We evaluated the
correlation between Gleason score on biopsy and prostatectomy
specimen.
Methods: We evaluated 324 prostates diagnosed with prostate
adenocarcinoma from which 270 were valid for the study. The mean
patient age was 61,3 years with an average ultrasound volume
of 51,6 cc and PSA 9,34 (3,5-26) ng/ml. In 183 patients without
previous biopsies and 4 with an average of 3 previous biopsies,
digital rectal examination was normal in 54% of the cases.
Results: In 67% (180) of the cases, the biopsy showed a Gleason <7,
in 31% (85) Gleason 7, and in 2% (5) Gleason >7. Of the
prostatectomy specimens, 62% (162) were Gleason 7, 4% (10)
Gleason >7, and in 8 no tumor was found. Comparing the Gleason
biopsy with radical prostatectomy there was concordance in 56,5%
(148). Laterality was concordant in 53% (139). Both Gleason and
laterality was consistent only in 36% (94) of cases.
Conclusions: Prostate biopsy underestimates the prostatectomy
Gleason score in 36% (97) of the evaluated patients and overvalues
it in 3% (8) of men.
59
Early response in alkaline phosphatase as an independent
predictive factor for disease progression in castration-resistant
prostate cancer patients with post-chemotherapy PSA elevation
Hong SJ, Han KS. Urology, Department of Urology, Yonsei University College of Medicine,
Seoul, Republic of Korea
Introduction & Objectives: Prostate-specific antigen (PSA)
changes during the early phase of chemotherapy are known to be
inaccurate surrogates for outcome in castration-resistant prostate
cancer (CRPC). We investigated the potential value of serum
markers related to skeletal metastasis as differentiating and/or
surrogate biomarkers in CRPC patients.
Materials & Methods: We retrospectively reviewed 83
patients with CRPC who received chemotherapy from 2002 to
2008. Baseline levels and serial changes of serum PSA, alkaline
phosphatase (ALP) and calcium were assessed. Pre-treatment
clinical data and follow-up serum markers were also evaluated. We
analyzed the relationship between serum markers and PSA flare
and outcomes.
Results: Of 61 patients, PSA initially increased in 33 patients
(54.1%) and PSA flare occurred in 14 (22.9%). Of the 14 patients
with PSA flare, the initial ALP increased in 2 (14.3%) and the initial
calcium level increased in 5 (35.7%). In contrast, of the 19 patients
with PSA progression, the initial ALP increased in 16 (84.2%) and
calcium increased in 9 (47.4%). Multivariate analysis showed that
only an initial change in ALP was associated with the occurrence
of PSA flare. In addition, outcome analyses revealed that an
initial increase in ALP and PSA were independently associated
with disease progression, but only an initial change in ALP was
a significant predictor for progression in patients with an initial
increase in PSA.
Conclusions: The early response in ALP level after chemotherapy
is a differentiating marker between PSA flare and PSA progression
and is an independent predictive marker for progression-free
survival in CRPC patients with post-chemotherapy PSA elevation.
60
Diagnosis of anterior prostate cancer using MRI/TRUS real time
soft image fusion
Baco E1, Rud E2, Svindland A3, Eggesbø HB 4. 1Urology, Oslo University Hospital, Aker,
Oslo, Norway; 2Radiology, Oslo University Hospital, Aker, Oslo, Norway; 3Pathology,
Oslo University Hospital, Radiumhospitalet, Oslo, Norway; 4Radiology, Oslo University
Hospital, Rikshospitalet, Oslo, Norway
Background: Anterior prostate cancers are rarely palpable and
difficult to sample when using traditional transrectal ultrasound
(TRUS) biopsies. Accurate targeted biopsies can be performed
when using magnetic resonance imaging (MRI) and 3D TRUS
abstracts ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������� 51
real time soft image fusion. The aim of the study was to evaluate
the accuracy of MRI/TRUS guided biopsies in the detection of
anterior prostate cancer.
Materials & Methods: Between 2010 and 2012, 358 patients
with elevated prostate specific antigen (PSA) underwent MRI/
TRUS guided biopsies. 90/358 (25%) pts with MRI suspicious
anterior cancer were included in the study. Biopsy patient groups
were: initial biopsy 5 pts, 1st -10th re-biopsy 63 pts (mean
previous negative biopsy procedures 2.6), re-biopsy due to active
surveillance 19 pts, and PSA recurrence after radiotherapy 3 pts.
Mean age, PSA and prostate volume were 65 years, 17.0 ng/ml
and 42 ml. MRI: 1.5T Avanto (Siemens, Erlangen) and body array
coil. Sequences: ax3D T2w, and DWI b2000 and b50/1000 were
used for apparent diffusion coefficient (ADC). Ultrasound: 3D
Accuvix V10 (Medison®, Korea), navigation system: Urostation
(Koelis®, Grenoble, France). Minimum one biopsy was obtained
from each MRI target using 18G Tru Core ®II (Angiothech, USA).
One sample T- test was used for statistics.
Results: 74/90 (82%) pts had positive targeted biopsies with
Gleason score 6 (n=25), 7 (n=34), 8 (n=14) and 9 (n=1), and mean
tumour volume 3.2 ml (95% CI 1.6-4.8). ADC values for positive
targeted biopsies were 78 x10-5mm2/s (95% CI 74-82) and for
negative targeted biopsies 97 x10-5 mm2/s (95% CI 90-104),
p<0.001. The mean number of positive targeted biopsies pr.
patient was 2.7, and the mean length of cancer pr. biopsy was 5.5
mm.
Conclusions: MRI/TRUS real time fusion biopsy technique is
accurate in diagnosing anterior prostate cancer.
61
Transperineal biopsies of the prostate as a primary modality
for histological diagnosis
Chang RTM1, Popert R1, Vyas L1, Morris E1, Tsui M1, Yamamoto H1, Duasko S1, Meiers I2,
Chandra A3, Challacombe B1, Cahill D1. 1Urology, Guy’s Hospital, London, United
Kingdom; 2Pathology, Bostwick Laboratories, London, United Kingdom; 3Pathology,
Guy’s Hospital, London, London, United Kingdom
Introduction: Screening studies indicate that in patients
undergoing primary transrectal sextant biopsies, 25% are
positive for cancer. This figure increases to 45% in extended
biopsy protocols, but there may still be under sampling of
the anterior peripheral zone of the prostate. We evaluated
transperineal sector biopsies (TPSB) of the prostate as a
primary modality for gaining histological diagnosis within
an asymptomatic cohort of patients who had undergone
PSA testing as part of a company routine health screening
assessment.
Patients & Methods: A total of 185 patients referred following
a routine general health screening assessment were included
in the study. The median age was 59 yrs and the median PSA
was 6.10 ng/mL (range 0.7 - 182 ng/mL). The transperineal
sector biopsies involved taking a total of 24 - 38 cores that were
peripherally directed, were done as a daycase procedure under
general anaesthetic without the need for catheterisation. We
set out to evaluate the cancer detection rate, characteristics and
location of cancers, clinical progress and complications.
Results: 137 (74%) patients had abnormal histology
comprising of acinar small cell proliferation (ASAP) (%), high
grade prostatic intraepithelial neoplasia (HGPIN) (%) or
adenocarcinoma. 116 patients (62.7%) had adenocarcinoma.
Of these patients Gleason sums of 6, 7 and greater than 7 were
seen in 75, 36 and 5 patients respectively. This left 69 patients
(37.3%) that had no evidence of invasive malignancy in which
48 patients had entirely benign histology (26%). Anterior
cancers were found in 38 patients (32.8%) and 17 patients
(15.3%) had cancer completely confined to the anterior sectors
only. Following the transperineal sector biopsies, 30 patients
commenced active surveillance, 39 with low risk disease had
dynamic brachytherapy, 30 had radical robotic prostatectomy
and the remaining 17 patients had either hormones and/or
external beam radiotherapy. 4 patients had retention of urine
and 3 patients had haematuria requiring overnight stay. No
urosepsis or urinary tract infections requiring antibiotics were
observed.
Conclusions: Primary transperineal sector biopsies are
safe, offer high cancer detection rates and aid treatment
stratification.
62
Hospitalization itself decreases the serum prostate-specific
antigen values compared to the outpatient values in patients
with benign prostatic diseases
Kim SJ, Yoon IS, Shin TY, Cho DS, Kim S, Choi JB, Ahn HS, Kim YS. Urology, Ajou
University School of Medicine, Suwon, Republic of Korea
Objectives: There have been a few reports about the
discrepancy between outpatient and inpatient serum prostatespecific antigen (PSA) values in the same man, addressing
that the lack of activity associated with bed rest during
hospitalization might decrease the serum PSA values. This study
was performed to investigate whether the hospitalization itself
may influence the serum PSA values.
Methods: Transrectal ultrasound-guided prostate biopsies
were performed for detecting prostate cancer in 2,017 patients
between February 2001 and April 2011 at our institution.
Among them, 416 patients were hospitalized for prostate
biopsies and the serum PSA values were checked at outpatient
department (OPD) within 1 month before admission and also
just after admission, and the results of the prostate biopsies
revealed no evidence of cancer. We retrospectively reviewed the
data of the 416 patients and compared the serum PSA values
checked at preadmission OPD and during hospitalization.
Results: Among a total of 416 patients, the interval between
the 2 PSA measurements was 22.2 days (range, 3-30 days) and
the prostate size measured by transrectal ultrasonography was
53.63 cc (range, 12.8-197.9 cc). Among a total of 416 patients,
mean serum PSA levels checked during hospitalization were
significantly lower than those checked at OPD (6.69 ng/ml vs.
8.01 ng/ml, p<0.001). When stratified according to age, the
presence or absence of chronic prostatitis in biopsy pathology,
serum PSA levels, and prostate size, the serum PSA levels
checked during hospitalization were significantly lower than
those checked at OPD in all subgroups, except in cases with age
20-39 years and PSA level less than 4 ng/ml, which showed no
significant differences.
Conclusions: Hospitalization itself decreases the serum PSA
values compared to those checked at OPD in patient with benign
prostatic diseases. Therefore, the serum PSA values should be
checked on an OPD basis for the serial monitoring of PSA levels.
52 ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������ abstracts
63
Efficacy and tolerability of 3- and 6-month depot formulations
of leuprorelin acetate for advanced prostate cancer in daily
clinical practice: pooled data from 2 non-interventional studies
Ohlmann CH1, Gross-Langenhoff M2, Tunn UW3. 1Department of Urology, Saarland
University, Homburg/Saar, Germany; 2Medical Department, Astellas Pharma GmbH,
Munich, Germany; 3Urological Department, Urological Clinic Fachartzentrum Klinikum
Offenbach, Offenbach/Main, Germany
Introduction & Objectives: Androgen-deprivation therapy is
the current standard therapy for advanced prostate cancer (PCa).
This therapy often consists of injections of luteinising-hormonereleasing-hormone (LHRH) agonists. The LHRH agonist
leuprorelin acetate (LA) is available in several formulations,
including 1-, 3- and 6-month biodegradable polymer matrix
depot formulations (Eligard®), which have been shown to reduce
testosterone and PSA levels in several clinical trials (Crawford
ED et al. J Urol 2006;175:533-6/Perez-Marrero R et al. Clin Ther
2002;24:1902-14/Chu FM et al. J Urol 2002;168:1199-203). The
current study aimed at monitoring efficacy and tolerability of
these formulations in PCa patients seen in daily clinical practice.
Methods: Two prospective, open-label, non-interventional
studies were conducted in Germany. 1,906 advanced PCa patients
starting treatment with either the 3-month (22.5 mg) or the
6-month (45 mg) LA depot formulation (Eligard®) were followed
during 12 months by 662 office-based urologists. Primary efficacy
parameters total serum testosterone and PSA were measured
at baseline and every 3 (for 22.5 mg dose) or 6 (for 45 mg dose)
months until 12 months after treatment initiation. Physicians
were also asked to rate ease of use and local tolerability of the
treatment.
Results: Median testosterone levels were reduced by 90%
from 88.8 ng/dl to 8.9 ng/dl 12 months after treatment start.
Testosterone reduction below the castration level was achieved
both in treatment-naïve patients and in patients pretreated with
LHRH agonists. Median serum PSA levels were reduced by 96%
from 12.2 ng/ml to 0.5 ng/ml 12 months after treatment start.
About 2/3rd of physicians found handling of the prefilled syringe
(very) convenient, while >90% rated local tolerability as good or
excellent. Adverse events (AEs) occurred in 8.8% of patients, with
injection site pain and hot flushes being the most common ones.
Conclusions: These data confirm that the 3- and 6-month LA
depot formulations reduce testosterone and PSA levels to a
similar extent in daily clinical practice as in clinical trials, both
in treatment-naïve and in pretreated patients. This study also
confirms the good tolerability of the 3- and 6-month LA depot
formulations. The majority of physicians found handling of the
prefilled syringe in routine clinical practice (very) convenient.
64
Preoperative prognostic factors fail to predict one lobe
involvement in patients with clinically insignificant prostate
cancer
Andrianov AN, Nyushko KM, Vorobyev NV, Alekseev BY. Urology, Moscow Hertzen
Oncology Institute, Moscow, Russian Federation
Objectives: The aim of the study was to assess pathological
outcomes after radical prostatectomy (RPE) in pts with
unilateral low volume and low grade PCa and evaluate prognostic
significance of preoperative clinical parameters regarding
postoperative tumor stage and grade.
Materials & Methods: 94 pts were selected for analysis
according to preoperative criteria of insignificant PCa. Mean age
of patients was 62.3±6.4 (47-74) years. PSA level ranged from 1.1
to 10 ng/ml (mean – 6.8±2.2). Median percent of positive cores
was 18.9±10.1% (7.7-33.3%). Clinical stage T1b was diagnosed in
6 (5.3%) pts, T1c – in 59 (52.7%) pts, T2a – in 47 (42.0%) pts.
Results: The pathological stage pT0N0 was determined in 8
(7.1%) pts. After postoperative morphology 10 (8.9%) pts
demonstrated upgrade of GS, upgrade of stage from localized to
extracapsular and metastatic (pN+) disease was determined in 12
(10.0%) pts and 3 (2.7%) pts. Bilateral tumor extent was revealed
in 63 (56.3%) pts. Clinical stage (p=0.9), number of biopsy cores
(p=0.8), PSA level (p=0.5), body mass index (p=0.3), prostate
volume (p=0.2) and biopsy GS (p=0.2) didn’t significantly
correlate with probability of pathological upgrade of PCa.
Conclusions: The clinical criteria of low volume and low grade
PCa are useful for selection of pts for ablative therapy because
the rate of stage and grade upgrade after RPE was in our study
only 23.3%. On the contrary these parameters are not suitable
for prediction of only one lobe involvement (upgrade to bilateral
extent was 69.6%) and can’t to be used in planning of unilateral
ablative therapy.
65
Prostate cancer gene 3 (PCA3) in postoperative prognosis after
radical prostatectomy – initial experience
Belej K, Kaplan O, Kohler O, Kocarek J, Chmelik F. Urology, Central Military Hospital,
Prague, Czech Republic
Introduction & Objectives: Current prognostic factors in
prostate cancer (PC) patients before radical prostatectomy are
not precise and they usually change in the majority of patients
after surgery. There is a big afford to find new prognosticators
which can predict results of procedure. More reliable parameters
will allow proper use of all technical alternatives available –
uni/bilateral nerve-sparing, bladder neck-sparing etc. Role
of prostate cancer gene 3 (PCA3) was evaluated in a pilot
prospective study.
Methods: Robotic-assisted extra-peritoneoscopic radical
prostatectomy (RARP) was performed in consecutive patients
with histologically proven PC. Patients indicated for surgery
had T1-T3 (non-bulky) cancer and were eligible for general
anesthesia with no other restriction according to other factors.
Common prognostic factors (T stage, Gleason score (GS),
PSA, number of positive cores, laterality, prostate volume)
were evaluated. Commercial kit for PCA3 detection in urine
(ProgensaTM, Gen-Probe Inc., USA) was added as new factor and
its level in first catch urine after digital rectal examination of
the prostate was displayed as PCA3 score (PCA3 mRNA and PSA
mRNA ratio x 1000).
Results: In 76 patients with average age of 64 years (46-72
years) and average PSA level of 5.8 ng/ml (2.1-21.7 ng/ml),
51 of 75 (68 %) patients had localized PC (pT2) and 64 of 75
(85 %) men had GS ≤ 7. One patient had pT0 finding. PCA3 in
urine was detectable in all but one patient (3rd in order) and
no inconclusive result was found in evaluable men. PCA3 score
didn´t correlate with prostate volume, serum PSA level and
number of positive cores (p > 0.05). Significant correlation
between pathological T stage (pT) and PCA3 was found. Other
patholological factors (GS, laterality) were independent of PCA3
score.
abstracts ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������� 53
Conclusions: Based on this pilot study PCA3 score can predict
pT stage after radical prostatectomy and no other available
factors were correlated with PCA3 level in urine. These
preliminary results must be confirmed by larger study and
multivariate analysis which can evaluate role of PCA3 more
precisely.
Project was supported by Tomas Bata Foundation.
66
Nurse practitioner-led telephone follow-up service for stable
prostate cancer: patient satisfaction
Turner B1, Tanabalan C1, Pati J1, Nargund V 1, Wells P2. 1Urology, Homerton University
Hospital, London, United Kingdom; 2Clinical Oncology, Homerton University Hospital,
London, United Kingdom
Introduction & Objectives: The telephone follow-up service
is based on the premise that PSA measurement can be used as a
surrogate for outpatient attendance with the core of the service
being an approved and comprehensive protocol in which any
break will trigger a medical referral. The telephone follow-up
service has served to reduce the number of patients coming to
the hospital for appointments. This has led to an increased clinic
capacity and reduced waiting times, thus ensuring urgent care is
available for patients who need it.
This report aims to address patients’ experience of a nurse-led,
protocol-driven telephone follow-up service that was set up
for men with ‘stable’ prostate cancer, to ensure that patient
satisfaction and quality of care have been maintained.
Materials & Methods: Questionnaires and stamped addressed
envelopes were sent to all patients registered under the telephone
follow-up service. The survey was voluntary and anonymous
and patients were given 4 weeks to return the completed
questionnaire. The questionnaire consists of 10 closed-ended
questions and 1 open-ended question.
Results: In total, 40 questionnaires were sent out, 29 were
returned, yielding a response rate of 73%. Overall, the
respondents reported high satisfaction with the telephone
follow-up service (90% were either satisfied or very satisfied). In
terms of the consultations themselves, the majority of patients
found the length of the conversations to be ‘just right’ (93%)
with a lesser majority expressing that the calls were always
at times convenient to them (78%) and that they were always
called when they were told they would be called (74%). Patients
felt that the information given to them over the phone was
always easy enough to understand (89%) and the majority felt
that they always had the opportunity to ask questions during
the conversations (81%). When asked whether they would
prefer telephone follow-up or hospital follow-up, 79% of the
respondents reported that they would prefer telephone followup, citing convenience, time and privacy as the reasons for their
preference. 21% of patients would prefer hospital follow-up,
reporting ease of understanding, not liking the telephone and
preference for face to face contact.
Conclusions: The telephone follow-up service relieves pressure
on the Outpatient Department, increases capacity, reduces
waiting times and brings care closer to home. This report also
demonstrates that in general, patients perceive the service as a
valuable addition to their care and report high levels of satisfaction
with the service. It is worth noting, however, that a small number
of patients reported a preference for hospital-based follow-up. It is
recommended that patient preference is regularly assessed.
54
67
Incidental carcinoma of the prostate (IPCa) in Kosovo
Cuni Xh1, Haxhiu I1, Yusuf T 1, Cuni H1, Haxhiu A1, Xhani M2, Tartari F2, Bezhani E2.
1
Urology, University Hospital, Pristina, Kosovo; 2Urology, University Clinical Centre
Mother Teresa, Tirana, Albania
Introduction & Objectives: To determine the occurrence of
incidental carcinoma of the prostate (IPCa), in a group of patients
surgically treated (TURP and open adenoma enucleation) for BPE
in Kosovo. Information on IPCa in Kosovo is lacking. The present
investigation is first in Kosovo who was carried out to enlighten
IPCa among the operated patients diagnosed by BPE in a 5-years
cohort study.
Materials & Methods: This is hospital-based cohort study
conducted in Jan 2005-Dec 2010. The study comprised a
retrospective analysis of 2430 patients. The preoperative
variables analyzed were DRE, serum PSA value, and patient age.
Preoperatively all 2430 patients involved in this study had a
serum PSA value < or = 4.0 ng/mL without suspicious DRE and
age > 50 years.
Results: Out of 2430 cases operated for BPE, 130 (5.3%) of all
patients appeared to have IPCa. In all these cases the histological
findings reported adenocarcinomas, grade I-III, Gleason score 2-6
and 7-10. 103 patients were diagnosed with a T1a tumour and 37
patients with a T1b tumour of prostate. Prostate adenocarcinoma
identified by Gleason score: (G2-G6) were 65% (n = 90) of
cases, and (G7-G10) were 35% (n = 40) of cases. The other 2300
patients had postoperatively a histopathological result of benign
hyperplasia. The mean age among patients with IPCa was 73.9 ±
9.2 years, versus 69.0 ± 3.4 years among patients with BPE. The
advanced age (P = 0.004) was statistically related to the findings
of the surgical specimen analysis.
Discussion: The value of 5.3 % of patients with incidental
prostate cancer can be explained by the population structure of
Kosovo characterized as youngest population in Europe, where
60% of the population belongs to the age group of 25-35 years.
From the present study we can conclude that the older the age
of the patient with BPE is followed by greater possibility for
IPCa. Incidental PCa may appear even in patients with normal
preoperative serum PSA (value < or = 4.0 ng/mL), with no
suspicious DRE and age >50 years.
68
Multidisciplinary, multiprofessional management of prostate
cancer patients: is it really feasible?
Magnani T 1, Salvioni R2, Villa S3, Bellardita L1, Nicolai N2, Procopio G4, Avuzzi B1, Bedini
N3, Biasoni D2, Donegani S1, Rancati T 1, Marenghi C1, Stagni S2, Verzoni E4, Zaffaroni
N5, Valdagni R1,3. 1Prostate Cancer Program, Fondazione IRCCS Istituto Nazionale dei
Tumori, Milan, Italy; 2Urologic Surgery, Fondazione IRCCS Istituto Nazionale dei
Tumori, Milan, Italy; 3Radiation Oncology 1, Fondazione IRCCS Istituto Nazionale dei
Tumori, Milan, Italy; 4Medical Oncology, Fondazione IRCCS Istituto Nazionale dei
Tumori, Milan, Italy; 5Molecular Pharmacology, Fondazione IRCCS Istituto Nazionale
dei Tumori, Milan, Italy
Cancer patients are better managed in a multidisciplinary
(MD) setting. It should be more so with prostate cancer (PC),
which, depending on the risk class, has multiple therapeutic and
observational options.
Our PC Programme was established in 2004 as a translational,
MD and multiprofessional project.
First steps: 1) to build a MD team with urologists, radiation
������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������
abstracts
oncologists, medical oncologists, psychologists, palliative care
experts, uropathologists and radiologists; 2) to share and adopt
diagnostic and therapeutic guidelines; 3) to start a MD clinic
(March 2005) organized in:
Friday clinic: urologist, radiation oncologist and psychologist
(medical oncologist on demand) examine PC patients
synchronously:
Monday: case discussion (CC) to share the decisions taken
on the MD cases, evaluate adherence to guidelines, perform
quality checks on the MD working, discuss problematic cases on
observation and complex cases seen monodisciplinarily.
The MD team became multiprofessional by including
professionals (project manager, secretary, data manager, nurse).
From March 2005 to March 2012, 2760 MD clinics were
performed. The organizational model was modified to better
performance and service.
Considering the high % of low-risk PC patients referring to the
MD clinic of our Institution (61% in 2009) and included in active
surveillance protocols (342 patients in Feb 2012), resources have
been increased to better manage this sub-population and reduce
the % of lost to follow up (2%).
The low % of advanced and metastatic PC patients (5% in 2011)
induced to organize the MD lists according to the risk class with
the medical oncologist on demand.
The efficacy of our MD clinic is demonstrated in the drug
therapies prescribed outside our Institution and terminated by
the MD team (11%). The efficacy of the CC is demonstrated in
the % of indications formulated in the MD clinics and changed
in the following CC (6%) as a result of quality checks of our own
performance.
The MD approach is proving successful. Strategies are agreed
on, complex cases managed multidisciplinarily, responsibility
on critical issues is shared and the psychologists’ insights help
to consider the role of education-related and cultural factors in
patients’ decisions. The CC discussion is fundamental to learn
the MD working, create a shared MD know how and approach the
patient as a subject of care rather than a disease to cure.
Special thanks to Fond. ProADAMO and Fond. Monzino for their
support
69
What are the mechanisms underlying the improved prostate
cancer (PCa) control with degarelix compared to leuprolide?
Van Poppel H1, Damber J-E2, Persson B-E3. 1Department of Urology, University
Hospital Gasthuisberg, Leuven, Belgium; 2Department of Urology, Sahlgrenska
Academy, University of Gothenburg, Gothenburg, Sweden; 3Ferring Pharmaceuticals,
St-Prex, Switzerland
Introduction: Degarelix and leuprolide were compared in a
1-year, randomised PCa study (CS21). In CS21A (long-term
extension), leuprolide patients were crossed over to degarelix.
Tumour control was more effective with degarelix vs leuprolide in
these studies (see Van Poppel & Klotz, Int J Urol 2012, in press);
here, we assess differences in their pharmacological profiles that
could account for clinical differences.
Cancer control: In CS21, degarelix reduced prostate-specific
antigen (PSA) significantly faster than leuprolide and led to
a 34% improvement in PSA progression-free survival (PFS).
After crossover from leuprolide to degarelix, PSA PFS improved
from 0.2 to 0.08 events/year (p=0.003; 27.5-month follow-up).
In patients with baseline PSA >20 ng/mL, time to progression
or death was delayed >7 months for degarelix vs leuprolide. In
those with metastatic disease, there was better control of serum
alkaline phosphatase with degarelix vs leuprolide (p=0.014),
indicating that degarelix prolongs control of skeletal metastases.
Improvements in quality of life global health status scores were
also significant for degarelix vs leuprolide.
Effect on gonadotrophin-releasing hormone (GnRH) receptors:
Differential effects of GnRH agonists and antagonists on the
pituitary are well established (see below). Differential effects on
peripheral GnRH receptors may also impact on clinical outcome.
Testosterone control: In CS21, degarelix led to an immediate,
profound testosterone suppression, which was maintained during
CS21A. In contrast, leuprolide caused an initial testosterone
surge and subsequent microsurges. The importance of long-term
testosterone suppression is increasingly recognised, eg high
testosterone levels correlate with increased mortality risk in
metastatic disease.
Follicle-stimulating hormone (FSH) control: There was
immediate and sustained FSH suppression in the degarelix group
in CS21 and CS21A. With leuprolide, there was an initial increase
in FSH and suppression, once achieved, was not maintained on
the long term. After crossover from leuprolide, FSH decreased
to levels seen with continuous degarelix. Interestingly, FSH
stimulates growth of hormone-refractory PCa cell lines and
in man, FSH levels are significantly higher in those with more
advanced disease.
Conclusions: Degarelix improves PCa control vs leuprolide.
This reflects differential effects on GnRH receptors and in
turn, testosterone, FSH and PSA, all of which have prognostic
significance in PCa.
70
Transperineal sector biopsies (TPSB): the technique and
morbidity
Popert R, Chang RTM, Vyas L, Kinsella J, Cahill D. Urology, Guy’s Hospital, London,
United Kingdom
Introduction & Objectives: Transperineal (TP) mapping
biopsies taking 40 - 90 cores are associated with urinary
retention in 10 - 17% and are labour intensive. We report on a
simplified transperineal sector biopsy (TPSB) protocol which we
have incorporated into our active surveillance (AS) programme.
We describe our technique and report our complication rates.
Materials & Methods: The protocol was developed from our real
time peripherally loaded brachytherapy technique. The prostate
is divided into 6 - 8 sectors; right and left sides are subdivided
into anterior, mid gland and posterior sectors with additional
basal biopsies for glands larger than 30cc. Geographical 3D
interpretation can be facilitated by placing individual cores from
each sector on to sponges with the cores laid from medial to
lateral (a - d). The most medial core (a) is inked at the basal end,
allowing the pathologist to report on the medial to lateral and
apico - basal distribution of the tumour (see diagram).
Results: 775 patients with known or suspected have undergone
TPSB. 205 patients have entered our AS programme, 247
patients have required active intervention, the remainder were
benign and have been discharged to their primary physician.
Complications include retention in 2% and haematuria requiring
admission in 1%. Urosepsis requiring admission has not occurred
although in 1% urine infections occurred, associated with bladder
outflow obstruction.
abstracts ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������� 55
Conclusions: TPSB are safe with a better complication profile
than more extended protocols. It allows more confident risk
stratification of patients, particularly with regard to suitability
for AS and the planning of active intervention. The 3D
geographical information obtained can be used to optimise nerve
sparing techniques in radical prostatectomy, provide preferential
loading in brachytherapy and targeted treatments in focal
therapy.
clinical situation permits, would minimise the risk of BRONJ by
reducing anti-angiogenic effects of bisphosphonate. Long-term
surveillance and maintenance of good oral and dental hygiene by
dental practitioners or community dental services are paramount
because the half life of bisphosphonate is up to 10 years as it is
absorbed into hydroxyapatite within the jaw bones.
72
71
Reducing the risks of bisphosphonate-related osteonecrosis
of the jaw among metastatic cancer patients requiring IV
bisphosphonates
Tanabalan C1, Turner B1, Ali S1, Pati J1, Wells P2, Cheng L3, Ali E3, Nargund V4. 1Urology,
Homerton University Hospital, London, United Kingdom; 2Clinical Oncology, Homerton
University Hospital, London, United Kingdom; 3Maxillofacial Surgery, Homerton
University Hospital, London, United Kingdom; 4Urology, Homerton University Hospital,
London, United Kingdom
Introduction: Bone metastases are a common feature of advanced
cancer and are associated with morbidity and mortality and are
of particular concern in prostate and breast cancer due to the
prevalence of these diseases. In addition to the immeasurable effect
to the patient, skeletal-related events (SRE) are costly to health
services in terms of patient encounters, resources utilization and
cost. Each SRE is estimated to cost an average of £2000.
Bisphosphonates have been used effectively for osteoporosis,
some cancers and multiple myeloma by inhibiting bone turnover
and osteoclastic function. The management of the rare but
serious side effect bisphosphonate-related osteonecrosis of the
jaw (BRONJ) is less well documented due to the lack of consensus
or guidelines.
All patients with metastatic prostate and breast cancer requiring
IV bisphosphonates are managed in our uro-oncology nurse
practitioner-led bone support clinic.
Aim: In order to avoid risks of BRONJ among cancer patients
requiring bisphosphonates, we have arranged a fast track referral
system to our Oral and Maxillofacial Surgery Department for
oral assessment and atraumatic removal of dentition prior to the
commencement of bisphosphonate therapy.
Materials & Methods: The uro-oncology nurse practitioner
leads a metastatic bone cancer clinic and faxes a fast track
referral letter to the Maxillofacial surgery team. Clinical and
radiological assessment of dentition is undertaken before
bisphosphonate therapy begins. The necessary extraction or
surgical removal of teeth/roots are carried out atraumatically
and primary mucosal closure with resorbable sutures wherever it
is possible.
Patients requiring dental restorations are referred to a dedicated
community dental service.
Results: 20 patients with metastatic cancers have been referred
through the fast track system for oral/dental assessment. 5
patients were not referred as they did not have teeth. 19 patients
required dental treatment before commencing treatment with
bisphosphonates. None of our patients have developed symptoms
of BRONJ.
Conclusions: Early atraumatic removal of teeth/roots and
primary mucosal closure to cover the healing alveolar bone
before the start of bisphosphonate therapy are key to prevent
the risk of BRONJ. For patients already started bisphosphonate
treatment, the cessation of bisphosphonate for 3 months if the
SOCS3-proteins seem to identify a subset of prostate cancer
with more aggressive behavior. Immunohistochemical analysis
in a cohort of patients affected by prostate cancer: preliminary
result
Calarco AC1, Recupero SM1, Pinto F 1, Totaro A1, Pierconti F2, Martini M2, Bassi PF 1.
1
Urology, Catholic University School of Medicine “A. Gemelli” Hospital, Rome, Italy;
2
Pathology, Catholic University School of Medicine “A. Gemelli” Hospital, Rome, Italy
Background: Chronic inflammation may play a role in prostate
carcinogenesis. Molecular alterations of the Suppressor of
Cytokine Signaling (SOCS)-3 can contribute to explain the
pleiotropic role of interleukin (IL)-6 in this type of cancer.
Recently, the methylation of the SOCS3-gene was demonstrated
to cause the non-expression of the protein, thereby highlighting
its involvement in the pathogenesis of prostate cancer (PC)
and enabling identification of a subset of aggressive tumors.
We evaluated the expression of the SOCS3-protein in patients
(pt) with bioptically-diagnosed PC by immunohistochemical
analysis, something which is easier to perform, cheaper and more
reproducible compared to the DNA analysis.
Methods: We analyzed the protein expression of SOCS3 by
immunohistochemistry in 44 pt. Slides were incubated with
monoclonal antibody SOCS3 (1E4, 1.5 μg/ml; Abnova,Taiwan).
The SOCS3 staining intensity was evaluated by 2 pathologists (FP
and LML) in 3 different ways: positive (+), negative (-) and weak
(+/-). Colonic mucosa was used as positive control. 36/44 patients
underwent radical prostatectomy (RP).
Results: Biopsy Gleason score (Gs) was: <7 in 8 pt, 7 in 33 pt (3+4
pattern in 21 pt, 4+3 pattern in 12 pt), >7 in 3 pt. 8/8 (100%) pt
with Gs <7 and 7/33 (21%) with Gs 7 were SOCS+. 15/33 (45%) pt
with Gs 7 and 3/3 (100%) pt with Gs >7 were negative. In 11/33
pt (33%) Gs 7 a weak intensity was found so they were classified
as SOCS3 +/-.
25/36 (69%) pt who underwent RP were SOCS3- and 11/36 (30%)
SOCS3+. 12/25 (48%) SOCS3- pt had an organ-confined disease
(≤pT2), whereas 13/25 (52%) had an extraprostatic neoplasm
(5 pT3a [1 was N+], 6 pT3b, 1 pT4). All SOCS3+ patients (11/11)
had an organ-confined disease. 7/11 (63%) SOCS3+/- pt had an
extraprostatic neoplasm (>pT2).
Conclusions: SOCS3- pt turned out to have a more aggressive
disease compared with SOCS3+. In particular, also SOCS3+/- pt
tumors seemed to have an aggressive behavior.
The non-expression of the SOCS3-protein may identify prostate
cancer with more aggressive behavior and can be evaluated with
immunohystochemical analysis, which is a relatively easy and
cheap procedure in clinical practice. These results, if confirmed in
a wider population and with a longer follow-up, may encourage
research on the use of this molecular family as a prognostic
marker and a target for therapy with demethylating agents.
56 ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������ abstracts
73
Erectile function following robotic prostatectomy
Warren MA, Issa R, Anderson C, Perry M. Urology, St George’s Hospital, London,
United Kingdom
Introduction: The prevalence of erectile dysfunction following
treatment for prostate cancer varies widely in the literature. This
project assessed erectile function in patients following robotic
prostatectomy at St George’s Hospital in London and investigated
factors that may affect erectile function post-operatively.
Decisions & Outcomes: The calculus was endoscopically
removed under general anesthesia revealing its nidus on a
hemostatic clip. Patient symptoms resolved and he is clinically
well, continent and has a PSA of 0.03 ng/mL.
Conclusions: Laparoscopic radical prostatectomy is a technically
demanding operation. To the best of our knowledge we report
the first case of calculus formation around a hemostatic clip
at the vesicourethral anastomosis after laparoscopic radical
prostatectomy.
Methods: Questionnaires asking about urological symptoms were
posted to 150 patients who had undergone robotic prostatectomy
at St George’s more than 6 months previously. Erectile function
was assessed using the IIEF-5, an internationally recognised
and externally validated questionnaire. Responses were then
compared to clinical features of each patient’s treatment and
demographic factors. Pre-operative IIEF-5 scores were available
for a sub-group of 62 patients who had taken part in a previous
study and comparative analysis was also performed separately on
this group to assess the relevance of baseline erectile function.
Results: 105 completed questionnaires were returned (response
rate 70%), of which 59% scored below 5 out of a maximum 25
for erectile function. Age, ethnicity and pre-operative erectile
function were all significantly correlated with post-operative
IIEF-5 scores. Patients receiving adjuvant treatment also had
statistically worse erectile function than those who did not.
Clinical features of the cancer itself such as stage, PSA level
and prostate volume were not correlated with function postoperatively.
75
In multivariate analysis, age and black ethnicity remained
significant determinants of post-operative erectile function. This
remained the case for the sub-group with pre-operative IIEF-5
scores, which were also found to be a significant determinant of
post-operative function in multivariate analysis.
Abiraterone acetate for castration-resistant prostate cancer
following docetaxel: our initial experience
Conclusions: Assessing erectile function before surgery and
taking a patient’s age and ethnicity into account can give a good
indication of likely function after robotic prostatectomy. This is
useful for the counselling of patients prior to surgery. Patients
can also be advised that adjuvant treatment may further impact
functional outcomes.
Introduction & Objectives: Abiraterone acetate is a novel
systemic hormonal therapy for castration-resistant prostate
cancer (CRPC) patients. It potently blocks cytochrome P450C17
(CYP17), a critical enzyme in testosterone synthesis, thus
blocking androgen synthesis in the adrenal glands, testes and
within the prostate tumour. We present our initial experience
with abiraterone acetate, which was provided to our patients in a
compassionate use programme.
74
Materials & Methods: During a 14-month period, abiraterone
acetate (1 g, combined with 10 mg prednisone) was prescribed to
18 patients following docetaxel treatment. Data were collected
retrospectively. Follow-up schedule was a 2-weekly visit during
the first 2 months and thereafter monthly. Each visit included
history taking, clinical examination and serum analysis
(PSA, electrolytes and liver enzymes). Response was defined
as a PSA decline of ≥ 50%, stable disease was a PSA decline of
0-50%, while progressive disease was defined as a rising PSA.
Continuous values are expressed as mean (± standard deviation).
Mean patient age was 70,8 years (± 6,4). Gleason score was 6 in
2 patients, 7 in 2 patients and ≥ 8 in 9 patients. In 5 patients
Gleason score was unknown. Mean pre-treatment PSA level was
740,9 ng/ml (± 1681,9).
Vesicourethral anastomosis lithiasis after laparoscopic radical
prostatectomy
Ramos R, Rebola J, Silva J, Carneiro R, Lencastre J, Silva E. Urology, Instituto
Português de Oncologia, Lisboa, Portugal
Introduction: Prostate cancer surgical treatment with
laparoscopic radical prostatectomy is becoming more used for
due to its non-inferiority to standard open technique in cancer
control and rate of complications and superiority in terms of
post-operative patient recovery. Vesicourethral anastomosis is
one of the most demanding steps in this operation.
Case description: We present the case of a 57-year-old
man with the diagnosis of a Gleason 7 (3+4) prostate cancer.
Intraperitoneal laparoscopic radical prostatectomy was
performed and surgery was uneventful. Six weeks afterwards the
patient started complaints of dysuria and frequency. Escherichia
coli urinary tract infection was diagnosed and treated twice. Due
to persistent symptoms an urethrocystoscopy was performed and
a fixed calculus was identified at the urethrovesical anastomosis.
Van Praet C1, Lumen N1, Rottey S2. 1Urology, Ghent University Hospital, Ghent,
Belgium; 2Oncology, Ghent University Hospital, Ghent, Belgium
Results: Eleven out of 18 patients (61,1%) benefitted from
treatment: 5 patients (27,8%) had a response, 6 (33,4%) had
stable disease, while 7 (38,9%) had progressive disease. Using
Kaplan-Meier survival curves, a median time to PSA or clinical
progression of 6,3 months was seen in responders and 2,1
months in patients with stable disease. Mean duration of
abiraterone acetate treatment in all patients was 2,8 months
abstracts ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������� 57
(± 2,3). Recorded complications were elevated liver enzymes (4
patients), hypokalaemia (1), anorexia (3), nausea (1), myalgia
(1) and diarrhoea (1). Until now treatment was aborted in 14
patients: due to biochemical or clinical progression in 12 patients,
elevated liver enzymes (> 5 times) in 1 patient and 1 patient died
during treatment.
9.4% of all cancers reported in Setif. The results suggest that
prostate cancer ranked second among male population and the
age-adjusted incidence rate increased quickly during these two
decades.
Conclusions: In our first series of patients treated with
abiraterone acetate, response or stable disease was recorded in
61% of patients with a median time to PSA or clinical progression
of 6,3 months in responders. Complication rate was fairly low.
These preliminary results tend to confirm the data from the
COU-AA-301 trial.
77
76
Trends in prostate cancer incidence in Setif, Algeria between
1987-2007
Zoubida Z1, Djamel A 2, Aicha DD3, Abbes M1, Slimane L1, Mokhtar HC1. 1Cancer registry
of Setif, University Hospital of Setif, Setif, Algeria; 2Anatomopathology, University
Hospital of Setif, Setif, Algeria; 3Anticancer center of Constantine, University Hospital
of Constantine, Constantine, Algeria
Introduction: Prostate cancer is very common and while the
incidence rate is rising quickly, in many countries, the mortality
rate has started to fall. While aggressive testing with prostate
specific antigen has contributed to this decline in mortality,
urological cancers comprise approximately one third of all
cancers diagnosed in men worldwide, and prostate cancer is the
commonest of these. The global burden of prostate cancer rose
from 200,000 new cases/year in 1975 to reach an estimated
700,000 new cases in 2002.
In Algeria, in 2002, prostate cancer was the eleventh most
common cancer in men with 466 cases (3.3%). Our study aimed
for adjusting prostate cancer incidence trends over the longest
period available (1987-2007) in Setif for the effect of age, sex,
and period of diagnosis and the geographical distribution. These
data were compared with standardized rates of Cancer Registries
in Five Continents.
Materials & Methods: Incidence data were collected in the
period 1987-2007 from the population-based cancer registry
of Setif. The software used was the Can Reg 4 produced by the
unit of descriptive epidemiology of the International Agency for
Research on Cancer (IARC), Lyon. France. Cancer morphology
and topography were coded in accordance to the International
Classification of Diseases for Oncology manual (ICD-O, the third
edition).
Results: In Setif, prostate cancer ranked second among the male
population. The incidence was highest among men in the 80-82
age group (51.7%) followed by men in the 60-64 (30%) and the
75-79 (16.3%) age group. The median age at diagnosis was the
65-69 age group.
Cases
1987-1989
1993-1997
2002-2007
25
71
192
%
3.7
5.2
9.4
ASR
2.9
4.3
8.2
(ASR per 100,000 males)
Age-adjusted incidence rate increased quickly from 2.9 per
100,000 men in 1987-1989 to 8.2 per 100,000 men in 2002-2007.
Conclusions: Prostate cancer was an important public health
problem in Algeria between 1987 and 2007. It represents
The treatment of local advanced prostate cancer according to
our experience
Haxhiu I1, Quni Xh1, Hyseni S1, Aliu H1, Haxhiu A 2, Haxhiu E2. 1Urology, University Clinical
Center of Kosovo, Prishtina, Kosovo; 2Medical Faculty, University of Prishtina,
Prishtina, Kosovo
Introduction & Objectives: Prostate cancer develops primarily in
men over fifty. Kosovo is the country with the youngest population
in Europe, with over 50% of them under the age of 28, and this
may be the reason why prostate cancer is the third most common
cancer, after the bladder and kidney, in our Clinic, beside the fact
that in the USA, Europe and many other countries around the
world, prostate cancer is the second most common cancer in males,
right after lung cancer. And of course we must not forget other
factors that contribute to this situation too, which include the
absence of health culture by our patients, the expensive diagnoses
for them and also, the missing experience of our physicians.
Our purpose was to give a full information about the incidence of
prostate cancer in Kosovo, the methods of treatment, especially
those for locally advanced prostate cancer, focusing more on radical
prostatectomy as a favorable choice.
Materials & Methods: This is a retrospective study. The material
gives information about the incidence and the type of surgical
intervention applied to the patients diagnosed with prostate
cancer which were admitted to our Urological Center (the only
tertiary center in Kosovo). 117 cases with prostate cancer were
processed, considering their age, the Gleason score and the type of
intervention. We have been more focused on monitoring and the
course of disease of the patients with locally advanced prostate
cancer.
Results: 117 patients were processed, to which surgical
intervention was applied, because of prostate cancer. We applied
radical prostatectomy in 38 patients, orchiectomy in 53 patients
(patients with advanced cancer), transvesical prostatectomy in 24
patients, only the biopsy in 1 patient and ureterocutaneostomy
in 1 patient. Before these interventions the sextant biopsy was
performed and the Gleason score ranged from 1-10. In 3 of them
the Gleason score was 10, with infiltration of the seminal vesicles,
and in 2 of them this score was 9. So it means that we dealt with
T3c and T3a stages or with locally advanced prostate cancer. In 2
cases radical prostatectomy with orchiectomy was performed, and
in the 3 other cases radical prostatectomy was performed with 2
cycles of Androcur. The course of the disease was followed for 2
years and it was seen that the first 2 cases had normal PSA levels
within 2 months and there was no tendency for these values to
increase. In 1 case, who was treated with Androcur, no evidence
wa seen of an increased PSA level. In the 2 other cases treated
with Androcur, the levels of PSA started to increase after 2 years.
These 5 patients were told to make a CT of pelvic and abdomen,
and since they turned out to be normal, we suggested them to have
subcapsular orchiectomy, and 1 month after the intervention the
levels of PSA were normal.
Conclusions: The treatment of locally advanced prostate cancer
(or T3) is still a controversial topic. Radiotherapy and adjuvant
androgen-deprivation therapy are considered standard treatment.
The guidelines of the EAU mention that radical prostatectomy is
an option for selected patients with small T3a, Gleason score of
58 ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������ abstracts
<8, PSA level <20 ng/ml, and a life expectancy of >10 years. Our
patients resulted with high levels of PSA; 120, 85, and 60 ng/ml,
for the patients with Gleason score 10, and 60 and 45 ng/ml, for
the 2 patients with score 9. All these 5 patients were operated 3,
respectively 2 years ago. Their course of disease was followed by
performing the CT and measuring the PSA levels every 4 months,
which showed us that there was no relapse, and their condition was
good (being able to do their daily activities and not complaining of
pain), so we came to the conclusion that radical prostatectomy can
be considered as a favorable choice even for patients with highly
advanced prostate cancer, and even when the Gleason score is 10,
and should be followed with androgen-deprivation therapy or with
subcapsular orchidectomy.
78
Moderately hypofractionated radiotherapy treatment using
tomotherapy for prostate cancer: toxicity analysis of 64
consecutive patients treated at the Radiotherapy Unit of AOU
Policlinico di Modena
Bruni A, Mazzeo E, Rubino L, Lanfranchi B, Bertoni F. Radiotherapy, AOU Policlinico di
Modena, Modena, Italy
Purpose: Curative treatment of patients with prostate cancer
(PC) comprises surgery, radiotherapy (RT) and/or hormone
therapy (HT). In external beam RT dose escalation is currently
investigated to improve outcomes in terms of dose-response
relation of local tumor control, biochemical progression free
survival and progression free survival. Dose escalation can
also be achieved by increasing dose per fraction above 2 Gy and
several studies showed that PC cells may be strongly susceptible
to this regimen due to their low α/β ratio. However dose
escalation and hypofractionation may also increase acute/late
toxicities, but the introduction of IMRT may allow us to deliver
higher doses without increasing toxicities.
Materials & Methods: From February 2008 to December
2011, 64 patients (pts) with PC underwent radical RT using
hypofractionation with or without concomitant HT. All of them
were treated using tomotherapy. Median age was 71 years. Eight
of 64 pts had low risk PC (12.5%), 4 intermediate risk (6.5%)
and 52 high risk (81%). About clinical stage, 13 pts had T1 PC
(20%), 7 T2 (10%), 10 T3a (15.6%) and 34 pts had T3b (53.1%);
pathological pelvic nodes were diagnosed in 5 pts (8%). Thirtyfour pts (53.1%) received neoadjuvant and/or concomitant HT,
while 30 pts (46.8%) received even adjuvant HT. Gleason score
was less than 7 in 23 pts, equal to 7 in 15 and superior in 16;
median Gleason score was 7. RT was delivered to a median dose
of 70 Gy in 28 daily fractions (2.5 Gy per day). Clinical target
volume included prostate in 2 pts, prostate and seminal vescicles
in 34 (53%); pelvic abdominal RT (with prophylactic intent)
was performed in 28 pts (43.7%) due to high risk of lymphatic
involvement (based on Roach algorithm).
Results: Median follow up was 20 months; 90% of pts (57/64)
are free from disease, 5 pts (8%) had locoregional relapse and 2
(2%) developed metastatic disease. RT was well tolerated with
only 4 pts complaining of acute severe urinary toxicity; 1 pt
developed a Grade 3 acute rectal side effect. Late Grade 3 rectal
toxicity was reported in 4 pts (6%) and Grade 2 urinary toxicity
in 3 pts (4%); no Grade 3 urinary late toxicity was found. No
treatment related deaths were encountered.
Conclusions: No increase of acute and severe side effects was
found. Hypofractionated dose escalated RT using tomotherapy
seems to be feasible and should be considered in the management
of prostate cancer in association with HT.
79
Analysis of the seminal vesicles biopsies protocol of the
Morales Meseguer Hospital
Montoya-Chinchilla R, Rosino-Sanchez A, Miñana-Lopez B, Pietricica B, Cano-Garcia
MC, Hidalgo-Agullo G, Reina-Alcaina L, Izquierdo-Morejon E. Urology, Morales
Meseguer Hospital, Murcia, Spain
Although new MRI techniques have high sensitivity for seminal
vesicle invasion, low availability and high cost involved makes it
necessary to incorporate cheaper and easier techniques that can
assist in the staging of prostate cancer. There are currently no
standard indication criteria for seminal vesicle biopsies. Due to
the lack of data in this field, an analysis of protocol biopsies of
the seminal vesicles of the Morales Meseguer Hospital has been
done. The overall rate of seminal vesicle invasion in our study was
15.7%, 25.58% if we only took into account patients diagnosed
with prostate cancer. All patients who were biopsied and showed
positivity in the three indication criteria for seminal vesicle
biopsies proposed, were T3b. Submit any alteration in prostate
base, either by physical examination or by ultrasound, has
shown a rate of 53.8% of T3b. To our knowledge, seminal vesicles
biopsies should be considered as a complementary procedure
for staging prostate cancer. It’s comfortable, cheap and with few
complications.
80
Metastatic cervical lymph node in prostate cancer
Pascual-Fernandez A, Calleja-Escudero J, Torrecilla García-Ripoll JR, Calvo-Gonzalez
R, Martín Martín S, Cortiñas González JR. Urology, University Clinic Hospital,
Valladolid, Spain
Background: Lymph node metastasis is an uncommon clinical
presentation in patients with prostate cancer and it could be
suggestive of the diagnosis of malignant lymphoma. Evaluation
of the PSA level and lymph node biopsy can lead to the final
diagnosis. Furthermore, the Gleason scores should be high in
almost all patients. The prognosis after such a presentation was
generally poor, with a mean survival of 18 months. Hormone
treatment has been shown to be of benefit even in patients in the
advanced stages.
Case presentation: We present the unusual case of a 77-yearsold male with a left neck mass for about 2 months associated to
weight loss, fatigue and hyporexia. He denies fever syndrome,
night sweats or pruritus. No lower urinary tract symptoms.
Cervical CT scan was performed, which showed two adenopathic
clusters of 21x23 and 25x27 mm in carotid-jugular area (image 1)
extending to left supraclavicular level with a noticeable increase
in caliber of the subclavian, axillary and proximal left humeral
vein compatible with deep vein thrombosis. In thoraco-abdominal
CT scan was objectified left axillary, paraaortic, retrocrurales
and throughout the retroperitoneum lymphadenopathy. Serum
prostate specific antigen (PSA) was 185.60 ng/ml. Digital
rectal examination revealed enlarged prostate with an uneven
surface. Cervical node biopsy showed adenocarcinoma that was
strongly positive for PSA and AE1-AE3 in immunohistochemical
study. Bone scan revealed no evidence of malignancy. Hormone
treatment was started with bicalutamide and leuprolide acetate.
Six months after initiation of treatment, the serum PSA declined
to 1.7 ng/ml. No evidence of significant lymphadenopathy in the
control CT scan. Nine months after diagnosis, the patient is still
alive.
Conclusions: Prostate carcinoma should always be considered
in the differential diagnosis of elderly men with cervical
abstracts ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������� 59
lymphadenopathy, even in the absence of lower urinary tract
symptoms.
Immunohistochemical stain of PSA can lead to the final
diagnosis, but PSA level must be perfomed. Once the diagnosis is
established, hormone treatment has been shown to be of benefit
even in patients in the advanced stages of the disease.
82
Sarcomatoid carcinoma of the prostate
Calleja-Escudero J, Calvo-Gonzalez R, Valsero-Herguedas E, Pascual-Fernandez A,
Bedate-Nuñez M, Pesquera-Ortega L, Cortiñas-González JR. Urology, University Clinic
Hospital, Valladolid, Spain
Background: Sarcomatoid carcinoma of the prostate is a
rare variant of prostate cancer, with few cases reported in the
literature up to date. Tumors are most commonly composed
of an admixture of both malignant glandular and spindle cell
elements. The sarcomatoid component can vary from 5 to 99%.
Case presentation: We present a case of solitary sarcomatoid
carcinoma of the prostate. It’s a 59-year-old man whose clinical
symptoms were dominated by dysuria and frequency. Digital
rectal examination showed a very large, hard and irregular
prostate. Serum PSA was 181 ng/ml. The patient underwent a
prostate needle biopsy and the histopathological examination
revealed poorly differentiated adenocarcinoma (Gleason score
5+4=9/10) in all cores of the left lobe and Gleason 7 (4+3) in
1 core of the right lobe. The bone scan showed multiple bone
metastases. He was treated with complete androgen blockade and
zoledronic. The PSA was 0,21 ng/ml 5 months after.
81
Prostate cancer in a Sub-Saharan Africa
Gueye SM, Jalloh M, Niang L, Ndoye M. Urology, Univeristy Cheikh Anta Diop and
Grand Yoff General Hospital, Dakar, Senegal
Background: Prostate cancer has the highest incidence and
prevalence of all cancers and in men it is the second non
cutaneous cancer after lung cancer. Scant data exist about
this cancer in developing countries especially in Sub-Saharan
Africa. But obviously there are rising trends on prostate cancer
prevalence in Africa. This will increase progressively. Africa is
experiencing an epidemiological transition from communicable
diseases dominated health care system to non communicable
diseases (NCDs) such as cancer, diabetes and cardiovascular
diseases. By the year 2020, over 70% of all cancer deaths will
occur in low- and middle-income developing countries (WHO).
The aim of this study was to review published data on prostate
cancer in Sub-Saharan Africa.
Materials & Methods: For this purpose, we searched for
publications in the literature in PubMed/Medline, African
Journals Online and Conference books of abstracts.
Results: Data show a limited knowledge of etiologic factors
and screening, generally advanced stage of the disease upon
diagnosis. Radical prostatectomy is safely performed for the few
localized disease patients; for the rest of the patients, hormonal
therapy is the major treatment option.
Conclusions: Limited data exist on prostate cancer in Senegal.
There are differences in clinical features of prostate cancer in this
part of the world. Late presentation is very common. The majority
of patients are referred at an advanced stage prompting palliative
therapy. Another problem is the lack of adjuvant therapy as
hormone therapy, chemotherapy and radiation therapy. Cultural
factors are limiting factors to castration. Radical prostatectomy
is safely performed for localized disease while radiation therapy
is unavailable in most of Sub-Saharan Africa.
60
He suffered from acute urinary retention after 3 months,
and underwent transurethral resection of the prostate, for
the treatment of bladder outlet obstruction. The pathological
specimen showed sarcomatoid carcinoma with squamous
differentiation. The time between the original diagnosis of acinar
adenocarcinoma and diagnosis of sarcomatoid carcinoma was 6
months. The patient died 7 months after diagnosis.
Conclusions: Sarcomatoid carcinoma is an aggressive variant
of prostate cancer, the prognosis of which is dismal regardless
of other histological or clinical findings. The pathogenesis of the
tumor is still uncertain but most likely represent a radiationinduced dedifferentiation of prostatic adenocarcinoma.
Approximately half of all patients develop metastatic disease
either at time of presentation or subsequently.
83
Conformal radiotherapy for high risk prostate cancer:
experience of the Radiotherapy and Oncology departement, Ibn
Rochd, Casablanca
Abdeslam H, Tarik C. Radiotherapy, CHU Ibn Rochd Casablanca, Casablanca,
Morocco
Introduction: High risk prostate cancer is, according to the
classification of D’Amico, defined as locally advanced (T2c and
above) or high grade (Gleason 4+3=7 and greater than 7) or
is associated with a total PSA value >20 ng/ml. The standard
treatment is a combination of conformal radiotherapy and
hormone therapy for the long term.
Materials & Methods: A retrospective study of 32 patients
with high risk prostate cancer who received the combination of
radiotherapy and hormone therapy between April 2009 and April
2011.
Results: The median age was 66 years (50-84). Stage distribution
was as follows: T1c 2, T2a 2, T2b 7, T2c 7, T3a 10, T3b 2 and
T4 2 with Gleason score 4-6 in 34%, 7 in 38% and 8-9 in 28%
of cases. The PSA value at diagnosis was less than 10 ng/ml in
16% of patients, between 10 and 20 ng/ml in 28% of patients
and more than 20 ng/ml in 56% of cases. 18 patients (55%)
������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������
abstracts
received hormone therapy including 13 patients who are still on
hormone therapy and 5 patients who have received for 3 years.
14 patients underwent surgical castration (46%). All patients
received conformal external radiotherapy, delivered by a linear
accelerator. The volumes irradiated were the prostate, seminal
vesicles and the ilio-obturator lymph nodes. The average dose
was 72 Gy (72-76). Only 1 patient received post-operative
radiotherapy at a dose of 60 Gy after radical prostatectomy
preceded by lymphadenectomy.
Evolution in short and long term was satisfactory with an
average PSA nadir of 0.255ng/ml (0002-2.2ng/ml). 5 patients had
complications (15%): 2 cases of post-radiation cystitis, 1 case of
post-radiation rectitis, 1 case of grade I dermatitis and 1 case of
urinary incontinence.
Conclusions: Our results are promising. External radiotherapy
combined with long-term hormone therapy is the standard
treatment for high risk prostate cancer. Realized in conformal
mode, it decreases urinary and rectal toxicity.
84
Peritoneal dissemination of prostate cancer with absence
of lymph node, skeletal or visceral metastases in a patient
scheduled to undergo robotic-assisted laparoscopic
prostatectomy
Labanaris AP1, Zugor V 1, Wagner C1, Afram S2, Witt JH1. 1Urology, Prostate Center
Northwest, St. Antonius-Hospital, Gronau, Germany; 2Pathology, Prostate Center
Northwest, St. Antonius-Hospital, Gronau, Germany
Introduction: We report a case of peritoneal dissemination of
prostate cancer (PCa) with absence of lymph node, skeletal or
visceral metastases in a patient scheduled to undergo roboticassisted laparoscopic prostatectomy (RALP).
Case description: In January 2012, a 62-year-old man was
referred to our department with a histological diagnosis of PCa,
cT2c cN0 cM0 Gleason 5+4=9. The initial diagnosis was made.
His serum prostate-specific antigen (PSA) level was 13.3 ng/
ml. Computerized tomography (CT) of the abdomen and thorax,
magnetic resonance imaging (MRI) of the pelvis and bone
scintigraphy showed no signs of metastasis. After the robot
was docked we noticed an odd macroscopic finding; adherent
white patches similar to that of leucoplakia spread on the whole
peritoneum, but mostly located under the bladder (Figure).
85
Clinical recurrence of prostate cancer with no change in PSA
Calleja-Escudero J, Calvo-Gonzalez R, Valsero-Herguedas E, Pascual-Fernandez A,
Bedate-Nuñez M, Pesquera-Ortega L, Cortiñas-González JR. Urology, University Clinic
Hospital, Valladolid, Spain
Background: Prostate cancer often metastasizes to the bones,
but it is rare that in patients with castration levels of PSA distant
spread takes place.
Case presentation: A 70-years-old patient with a PSA of 44.7 ng/
ml and a hard prostate on digital rectal examination. The biopsy
showed a prostate cancer Gleason 4+3 that affected more than
70% of the material. The patient was submitted to a CT and bone
scintigraphy which were negative for metastases. The patient was
treated with flutamide, goserelin and radiotherapy.
After 9 months and a PSA of 0.06 ng/ml, the patient experienced
bone pain. The bone scintigraphy showed metastases at D12-L1
and the left rib. The RMN identified a D12-L1 wedge fracture
without involvement of the spinal canal. Radiotherapy was applied
to D12-L2, and the patient received treatment with morphine and
zoledronic acid. The patient experienced persistent pain and was
operated by filling the spine with cement; kyphoplasty D12-L1.
Six years after continuous treatment with goserelin and zoledronic
acid, the patient showed a PSA of 0.6 ng/ml.
Conclusions: Although unlikely, castrate PSA levels in any clinical
manifestation may indicate spread of the disease.
Decisions & Outcomes: We performed a biopsy, sent it to
the pathologist for a frozen section analysis and continued the
operation. The diagnosis made was peritoneal cancer due to a
small cell undifferentiated cancer. At that time the pathologist
was not sure if it was metastasis due to the patients PCa or if it
was a metastatic tumor from his gastrointestinal tract. Thus, we
decided to perform only a diagnostic lymphadenectomy and end
the operation.
The final histology exhibited peritoneal cancer due to a PCa
Gleason 5+4=9 but tumor-free lymph nodes (0/15). A complete
androgen ablation was then initiated with an LH-RH agonist and
bicalutamide and in March 2012 the patient had a PSA value < 1
mg/ml.
Conclusions: In the future, diagnosis of this rare disease entity
will be the result of an extreme advance of the robotic technique
in comparison with other operative procedures; an enhanced
visibility. According to contemporary literature, treatment
should be performed in accordance with the standard strategy for
PCa, including hormone therapy and chemotherapy.
abstracts ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������� 61
86
Prostate cancer diagnosed at 28 years old – case report
Campos L, Rebimbas M, Mota Preto P, Sebastião C. Urology, HDES, Ponta Delgada,
Portugal
The status of rectum and bladder make the definite influence
on prostate location during radiotherapy. It is important for
treatment toxicity and response. In the presented case decreased
dopamine level influences rectum volume.
Case description: A 28-year-old caucasian male presented
with a painless dorsal curvature of the erect penis. He was
shown to have a PSA level of 3.4 ng/ml in a routine evaluation
made by his family practitioner. This PSA value was remeasured
and confirmed. Physical exam was normal and digital rectal
examination revealed a slightly enlarged prostate. His past
medical and family history was unremarkable.
Case presentation: We present a man with clinically T3aN0M0
III prostate cancer which was confirmed by histology. At the time
of admittance the patient did not report any urinary symptoms.
Medical history included Parkinson’s disease. Pretreatment PSA
was 4.7 ng/ml. A transrectal ultrasound-guided prostate needle
biopsy revealed prostate adenocarcinoma, with Gleason score 6
(3+3), from 1 lobe 4 positive scores and from the other 2 scores.
Whole body-bone scanning was normal. Pelvis MRI confirmed
T3a. The treatment was started with a LHRH-agonist, goserelin,
and the anti-androgen bicalutamide. The patient was included
in a single institution randomized trial comparing sequential
standard fractionated 2 stages vs whole pelvis IMRT radiotherapy
with hypofractionated simultaneous integrated boost (SIB)
IMRT. This patient was randomized to the SIB arm with 3.15 Gy
per fraction to be delivered to the prostate and seminal vesicles
and 2.2 Gy per fraction to lymph nodes in 20 fractions. On-line
CBCT setup before each treatment fraction was mandatory for
this trial. During the first fractions large variations in rectum
volume and position were observed. Therefore, targets and OARs
contours were deformed according to these day-to-day changes.
Several treatment plans were created accordingly and applied
depending on the day anatomy. The radiotherapy reactions were
evaluated with the RTOG questionnaire. After the treatment
completion the patient had general weakness. The only toxicity
observed up to date was acute GU - I grade, GI - 0 grade.
The penile curvature was corrected using the Nesbit procedure,
with satisfactory results. The patient was also submitted to a
transrectal ultrasound guided prostate biopsy. Prostate biopsy
revealed a Gleason score 6 (3 + 3) adenocarcinoma in 1 of 12
specimens.
Conclusions: The patient which otherwise would be excluded
from a randomized trial and most probably even the course of
standard RT would be compromised, was successfully treated as
planned with this daily adaptive radiotherapy. The toxicity was
GU - I grade, GI - 0 grade.
He underwent a radical retropubic prostatectomy and bilateral
pelvic lymph node dissection. The final pathology revealed a
Gleason score 6 (3 + 3) adenocarcinoma involving approximately
10% of the gland and no lymph nodes demonstrated metastatic
adenocarcinoma.
88
Three years after surgery, the patient has good oncologic control
and reasonable functional outcomes. PSA is under 0.001 ng/ml,
complete continence is achieved and erectile function is obtained
with inta-cavernosal prostaglandins.
Hainz H, Urology, Maria Hilf Krankenhaus Daun, Daun, Germany
Introduction: Prostate cancer is the fifth most common
malignancy worldwide and the second most common in men.
Its incidence and mortality rates vary significantly between
countries and regions. Evidence suggests that both genetics
and environment play a role in the origin and evolution of this
disease. However, increasing age is the most well-established risk
factor.
PSA (prostate specific antigen) was first identified and purified
in the late 1970s, but widespread use in clinical urology did not
occur for another decade. First used to monitorize treatment, its
importance was soon established in prostate cancer screening.
The optimal threshold of PSA serum level to recommend a
prostate biopsy has come under increasing scrutiny and the
standard value of 4 ng/ml is being redefined.
Conclusions: PSA-based screening has induced an important
age migration effect, such that the median age at diagnosis is
lower than before, with important implications for deciding on
the need for and type of treatment, as well as complications after
therapy.
To our knowledge, this is the youngest patient diagnosed with
prostate cancer.
87
Adaptive radiotherapy for prostate cancer with rectum
problems caused by Parkinson’s disease
Karklelyte A, Norkus D, Miller A, Valuckas KP. Radiotherapy, Institute of Oncology
Vilnius University, Vilnius, Lithuania
Introduction: The utilization of adaptive “plan of the day”
radiation therapy in case of complicated prostate cancer
treatment is not yet a widely recognized technique. We would like
to present a case report on prostate cancer of a 75-year-old man
with various rectum-associated problems during the course of
treatment, caused by Parkinson’s disease.
Laser will change surgery of geriatric oncology. Pattern could
be history of prostate therapy
Worldwide the ageing population needs more medicine;
especially minimally invasive surgery that should be affordable
everywhere. Prostate surgery started in 1901 when anesthesia
enabled painless Freyer. In 1970, TURP with transistors and
rodoptics was the first paradigm shift, followed now by laser.
Energy increase from the first Rubin laser in1961 enabled step by
step LLLT in the prostate; since 1991 coagulation (20W-NdYAG/
Hofstetter) and via cutting in 1998, vaporisation (PVP by 80W
KTPLaser/Malek&Kuntzman). With global 300000 PVP until
2007 and 80% of benign prostate enlargment-OP/USA 2010
(mostly outpatient therapy) it is new standard versus TURP.
Since 1988 we lasered 4000 tumours of the bladder and 2000
prostates. 1996 diodelaser enabled 95% of our surgery; so we
came out of “bloody medicine” to meet company to “human
treatment”. Most surgeons are not aware of a benefit of the
laser; the use of simple glass fibres for coagulation, cutting,
vaporisation and atomic photo ablation. The complications of
thousands of years old scalpel -<only costs> economically - are
reduced impressively. As we lasered transurethral prostate,
surgeons can perform minimally invasive or teleguided robot
operations with Seldinger punction and modern imaging system
in the body.
62 ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������ abstracts
Future of laser is an old dream of mankind to remove malignant
tissue without touching the body. New proton-laser Draco rom
FZD www.fzd.de generates and concentrates protons that destroy
tumours passing our body without much damage for surrounding
healthy tissue – e.g.CaP.
metastasis in a pelvic lymph node. He had regional volumetricmodulated arc therapy (VMAT) to a target gross tumor volume
with a cumulative dose of 78 Gy, and simultaneously VMAT to
a field of regional lymph nodes with a cumulative dose of 50 Gy.
He had grade 1 acute toxicity after the radiotherapy. During the
following 4+ months, PSA declined more than 50%. A repeat
[18F] FACBC PET/CT scanning showed a partial remission.
89
Conclusions: The effects and side-effects from using PET/CT
scanning and regional VMAT for lymph node-positive prostate
cancer surpassed expectations of Danish urologists.
Disseminated infiltration of bone marrow due to prostatic
adenocarcinoma: presentation of a case
Porfyris O1, Kontonis I2, Boutas L1, Tzelepis K 1, Kalomoiris P1. 1Urology, General Hospital
of Sparta, Sparta, Greece; 2Haematology, General Hospital of Sparta, Sparta, Greece
Introduction: Metastatic prostate cancer is a disease that
initially responds well to hormone therapy. Disseminated
infiltration of bone marrow due to prostate cancer is an unusual
manifestation.
Case description: We report a case of prostatic adenocarcinoma
with disseminated infiltration of bone marrow, refractory to
hormone therapy and with fatal outcome. A 74-years old man
was admitted to our department due to urinary retention,
haematuria and multiple ecchymoses. Laboratory findings were
as follows: Hb=7.9 g/dl, Ht=23.8%, WBC=4900/ml, PLT=35000/
ml, PSA=700 ng/ml. Microscopic examination of peripheral blood
showed anaemia, thrombocytopenia and leucoerythroblastosis.
Bone scan revealed multiple metastatic lesions. Bone marrow
biopsy revealed a hypocellular marrow with disseminated
infiltration of a poorly differentiated adenocarcinoma. Prostate
biopsy showed an adenocarcinoma of Gleason score 7 (3+4).
Decisions & Outcomes: The patient was treated with hormone
therapy, blood transfusions and erythropoietin. He did not
respond well to the therapy and died one and a half month after
admission due to brain haematoma.
Conclusions: Disseminated carcinomatosis to bone marrow due
to prostate cancer is rare and has a poor prognosis. It ususally
leads to disseminated intravascular coagulopathy. There are
no specific guidelines in the literature for the treatment of this
condition. Bone marrow infiltration may correlate with a more
aggressive subtype of prostate cancer, refractory to hormone
therapy.
90
Volumetric-modulated arc therapy for pelvic lymph node
metastasis of prostate cancer shown by anti-1-amino-Ffluorocyclobutane-carboxylic acid PET/CT
von Eyben FE. Internal Medicine, St Olavs University Hospital, Orkanger Hospital,
Orkanger, Norway
Introduction: Danish urologists claim that radiotherapy for
regional lymph node-positive prostate cancer is ineffective and
toxic.
Case description: A 50-year-old Danish man underwent a
radical prostatectomy for prostate cancer (pT3b, pN1, M0,
Gleason score 9 (4+5)). Postoperatively, he was given androgen
deprivation therapy. Prostate-specific antigen (PSA) declined to
unmeasurable levels but later showed a continuous rise to 1.1 ng/
mL 4 years after the prostatectomy. A MR scanning did not show
signs of metastases.
Decisions & Outcomes: A [18F] anti-1-amino-3-Ffluorocyclobutane-1-carboxylic acid PET/CT scanning showed a
91
EXMI therapy before and after radical prostatectomy
Jordan M. Urology, Private practice, Munich, Germany
I want to inform all urologists about the EXMI technology; its
value and advantages, and my experience of more than 13 years
with thousands of patients treated before and after radical
prostatectomy.
The EXMI-extracorporeal magnetic innervation is a technology
that received FDA approval for incontinence in women in 1998.
I learned about it at the first AUA meeting when this amazing
technology came on the market. As a specialist in the treatment
of incontinence I was so impressed about it that I decided after
only 10 seconds that I must own such a system.
After I got my first system in my practice I started offering it to
my patients and of course my first patient was an incontinent
male after radical prostatectomy. He was dry in 8 weeks. In the
next 2 months I had so many patients on therapy that I had
to acquire a second system. Now the EXMI is available in 56
countries.
The advantages of the EXMI, comparing the electro therapy, bio
feedback, kegel exercises, gymnastics and everything you know
as a conservative treatment of the pelvic floor are:
It is completely non-invasive. Patients stay fully dressed on
a chair, 2-3 times/week, for a total of 20 sessions, instead of
introducing probes 2 times/day for 6 months, doing unpleasant
kegel exercises or gymnastics. Electricity penetrates only 1.2-1.2
cm into the body and the EXMI up to 7.5 cm.
It is the only standard conservative therapy of the pelvic floor,
not depending on the patient, the physician or any other external
factors. The patients get up to 18,000 muscle contractions in a
20-minute session.
The compliance is almost 100%. The results depend on the
diagnosis and rate between 20-100%. We all know after we
made the diagnosis what % of improvement is to be expected, if
the patient does the treatment correctly. With the EXMI this %
comes true.
abstracts ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������� 63
Because it stimulates nerves you can treat effectively also OAB
and pain.
Authorlist
You can predict with about 10% the outcome if you did the
correct diagnosis.
A
It is the best financial help you can get into your business.
And for men, radical prostatectomy brings the risks of
incontinence and ED with it. EXMI is the instrument every one of
us needs in order to prevent and treat these problems effectively.
EXMI is life changing both for doctors and for patients.The XXIst
century urology without the EXMI is not acceptable any more.
Abbes M 58
Abdeslam H 60
Abu Eid R 39
Addali M 33
Afram S 61
Ahlering T 44, 49
Ahmad A 36
Ahn HS 48, 52
Aicha DD 58
Akhter W 36
Aksnes AK 26
Alekseev BY 27, 48, 53
Ali E 56
Ali S 36, 56
Aliu H 58
Alvisi MF 47
Ancheta J 36
Anderson C 30, 57
Andrianov AN 27, 48, 53
Andriole GL 35
Armstrong AJ 26
Audia S 28
Autier P 41
Avuzzi B 47, 54
B
Baco E 46, 51
Bailen J 36
Barbazza R 41
Bardelli I 49
Barua J 36
Bary P 29
Bassi PF 56
Bedate-Nuñez M 48, 51, 60, 61
Bedini N 39, 47, 54
Belej K 53
Bellardita L 46, 54
Benslimane L 35
Berge V 46
Berthold D 51
Bertoni F 59
Bezhani E 54
Biasoni D 47, 54
Bidair M 34, 36
Biggin C 26
Bonin S 41
Bordier B 40
Borghesi M 49
Bourgois N 28
Boutas L 63
Braeckman J 41
Brandenburg JJI 39
Brausi M 42
Brett A 30
Brown E 34
Bruland ØS 26
Bruni A 59
Burette R 28
Busby E 34
C
Cagna E 43
Cahill D 47, 52, 55
Calais da Silva FE 42
Calarco AC 56
Calleja-Escudero J 48, 51, 59, 60, 61
Calvo-Gonzalez R 48, 51, 59, 60, 61
Campos L 62
64
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abstracts
Cano-Garcia MC 59
Carbone A 50
Carneiro R 57
Carpentier P 49
Catania S 46, 47
Challacombe B 47, 52
Chandra A 52
Chang A 44
Chang RTM 47, 52, 55
Chapelon JY 46
Cheng L 56
Chi KN 26
Chinegwundoh F 36
Chmelik F 53
Cho DS 48, 52
Choi JB 52
Colecchia M 47
Collette ERP 30, 32
Collette L 51
Corbishley C 30
Corbusier A 28
Cortiñas González JR 59
Cortiñas-González JR 48, 51, 60, 61
Crouzet S 46
Cuni H 54
Cuni Xh 54
Cussenot O 38, 40
Cuzick J 36
D
Damber J-E 55
Damber JE 32
Dass RN 37
de Bono JS 26
de Braud F 39
Decaestecker K 31
De Coninck V 41
De Groote R 34
de Lange DCD 47
De Meerleer G 31, 34
De Naeyer G 49
De Potter A 45
Desai S 41
De Troyer B 31
Devcich G 29
De Visschere PJ 34, 45
D’Hondt F 34
Di Cristofano C 50
Djamel A 58
Donegani S 54
Duasko S 52
G
Gabriele P 43
Gattenloehner S 39
Gelet A 46
Germeau F 28
Gittelman M 36
Gjertsson P 32
Gonçalves F 42
Green J 36
Grivas N 40
Groskopf J 34, 36
Gross-Langenhoff M 53
Gueye SM 60
Gujral SJ 38
H
Habibzada J 30
Hainz H 62
Hamal M 28
Hamann C 37
Hamann MF 37
Hamberg P 37
Han KS 51
Hastazeris K 40
Hawaux E 29
Hawizy A 38
Haxhiu A 54, 58
Haxhiu E 58
Haxhiu I 54, 58
Heinrich E 50
Henderson RJ 36
Hertzman B 36
Hidalgo-Agullo G 59
Hines J 36
Hirmand M 26
Höglund P 32
Ho L 36
Holmes MA 29
Holz S 29
Hong SJ 51
Hong SY 48
Hoshinaga K 45
Hyseni S 58
I
Iken A 35
Ishise H 45
Issa R 30, 57
Izquierdo-Morejon E 59
E
J
Edenbrandt L 32
Efros M 36
Eggesbø HB 51
Egner T 50
Engel RP 30, 32, 47
Jalloh M 60
Jelski J 36
Jordan M 63
Juenemann KP 37
F
Faik M 35
Fellin G 43
Feng Z 34
Ferber A 50
Ficarra V 49
Fiorino C 43
Fizazi K 26
Fonteyne V 31, 34
Fossion LMCL 33, 39
Franco N 36
Fukami N 45
Fukaya K 45
K
Kaboteh R 32
Kafarakis V 40
Kagan J 34
Kalomoiris P 63
Kaplan O 53
Karklelyte A 62
Kelkar A 38
Khalil F 35
Khan Y 30
Kibel AS 34
Kim S 48, 52
Kim SJ 48, 52
Kim YS 52
Kinsella J 47, 55
Klaver OS 30, 32, 47
Klevecka V 27
Kliffen M 30, 32, 47
Kliment J 42
Klonowski W 39
Kocarek J 53
Kohler O 53
Kontonis I 63
Koziol I 36
Kröpfl D 27
Kusaka M 45
L
Labanaris AP 28, 30, 31, 33, 61
Laghi A 50
Lanfranchi B 59
Laungani RG 45
Lee A 36
Lencastre J 57
Leyland J 29
Limani K 29
Lin D 34
Liss M 49
Lomsky M 32
Lopes F 37
Lotan Y 34
Luedecke G 39
Lumen N 31, 34, 57
Lusch A 49
M
Maes H 31
Magnani T 46, 47, 54
Malavaud B 38, 40
Marchesin F 41
Marenghi C 46, 47, 54
Martini M 56
Martín Martín S 59
Maruyama T 45
Mauro FA 43
Mazzeo E 59
McMeekin F 36
Meesen B 40
Meiers I 52
Michielsen D 41
Miller A 62
Miller K 26
Miñana-Lopez B 59
Mokhtar HC 58
Monteiro H 37
Montoya-Chinchilla R 59
Morales B 44
Morris E 52
Mota Preto P 62
Mota R 37
Mottet N 38, 40
Mottrie A 31, 49
Mulders PFA 26
Musch M 27
N
Nargund V 54, 56
Naumann CM 37
Ndoye M 60
Neves T 37
Niang L 60
Nicolai N 47, 54
Nilsson S 26
Norkus D 62
Nyushko KM 27, 48, 53
abstracts ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������� 65
O
Ohlmann CH 53
Ohlsson M 32
Oliver T 36
Oosterlinck W 34
Osann K 44, 49
Osimani M 50
Ost P 31, 34
P
Palleschi G 50
Paolini B 47
Parker C 26, 38
Partin A 34
Pascual-Fernandez A 48, 51, 59, 60, 61
Pastore AL 50
Pati J 54, 56
Patil A 41
Peltier A 29
Perry M 30, 57
Persson B-E 55
Pesquera-Ortega L 48, 51, 60, 61
Petrozza V 50
Pierconti F 56
Pierris N 44
Pierzchalski M 39
Pietricica B 59
Pinney L 36
Pinto F 56
Plümmer J 27
Popert R 47, 52, 55
Porfyris O 63
Pracella D 41
Praet M 34
Procopio G 39, 54
Q
Queimadelos M 42
Quni Xh 58
R
Raina S 41
Rambaran SS 30, 32, 47
Ramos R 37, 57
Rancati T 43, 46, 47, 54
Rebimbas M 62
Rebola J 57
Recupero SM 56
Reina-Alcaina L 59
Rengo M 50
Robertson C 42
Rodrigues T 37
Roggenbuck U 27
Roggero E 41
Rosino-Sanchez A 59
Rottey S 34, 57
Rouviere O 46
Rozet F 38, 40
Rubino L 59
Rud E 46, 51
Ruffion A 38, 40
S
Saad F 26
Salvioni R 39, 46, 47, 54
Sanda MG 34
Sasaki H 45
Schatteman P 49
Scher HI 26
Schiefelbein F 50
66
Schoen G 50
Sebastião C 62
Segaran S 36
Selby S 26
Shin TY 52
Shiroki R 45
Siegel FP 50
Silva E 57
Silva J 57
Skarecky D 44, 49
Skolarikos A 44
Slimane L 58
Smets L 35, 38
Smit-Archer L 29
Sokoll L 34
Speakman M 36
Spencer M 37
Srivastava S 34
Stagni S 39, 54
Stamatiou K 44
Stanta G 41
Staudacher K 26
Stavropoulos NE 40
Stepien P 39
Stepien RA 39
Sternberg CN 26
Stoevelaar H 35, 38, 40
Suardi N 49
Svindland A 51
T
W
Wagenlehner F 39
Wagner C 28, 30, 31, 33, 61
Waliszewski P 39
Ward J 36
Warren MA 57
Weidner W 39
Wei JT 34
Wells P 54, 56
Wheatley Price P 37
Williams T 36
Witt JH 28, 30, 31, 33, 61
X
Xhani M 54
Y
Yamamoto H 52
Yoon IS 52
Yusuf T 54
Z
Zaffaroni N 54
Zoubida Z 58
Zou J 26
Zugor V 28, 30, 31, 33, 61
Tanabalan C 54, 56
Tanase M 39
Taneja S 34
Taplin ME 26
Tarik C 60
Tartari F 54
Taylor D 51
Terry B 36
Thompson I 34
Tombal B 35
Torrecilla García-Ripoll JR 59
Totaro A 56
Trojan L 50
Tsimaris I 40
Tsui M 52
Tunn UW 53
Turner B 36, 54, 56
Tzelepis K 63
V
Valdagni R 39, 47, 54
Valsero-Herguedas E 48, 51, 60, 61
Valuckas KP 62
van den Ouden D 47
van Dooren VPM 33
Van Leer P 28
Van Poppel H 55
Van Praet C 31, 34, 57
van Velthoven R 29
Vavassori V 43
Verbaeys A 34
Verzoni E 39, 54
Villa S 39, 47, 54
Villeirs G 31, 34, 45
Viterbo R 34
von Eyben FE 63
Vorobyev NV 27, 48, 53
Vyas L 47, 52, 55
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abstracts
published by:
e-HIMS
Duwijckstraat 17
2500 Lier, Belgium
F: +32 3 491 82 71
Prostate cancer
From diagnosis to managing
advanced disease
Proceedings of the Global Congress on Prostate Cancer
28-30 June 2012 – Brussels, Belgium