How to detect and investigate
Prostate Cancer before TRT
Frans M.J. Debruyne
Professor of Urology
Andros Men’s Health Institutes, The Netherlands
PRISM BRUGES
Recommendations for monitoring
prostate health before TRT
treatment
• Normal digital rectal examination (DRE)
• PSA <4.0 ng/mL
• Evaluate individual risk of prostate cancer
Recommendations for monitoring
prostate health during TRT treatment
•
Measure PSA At 3–6 months Annually or semiannually as
long as treatment continues
•
Perform DRE Annually or semiannually as long as treatment
continues
•
Refer for urological evaluation and possible prostate biopsy if
•
Prostate is abnormal on DRE or PSA >4 ng/mL or
•
PSA increase >1 ng/mL after 3–4 months on testosterone
treatment
•
Or PSA velocity >1.5 ng/mL/y or >0.75 ng/mL/y over 2 years
•
Or PSA velocity >0.4 ng/mL/y over an observation period of
<3 years (with PSA after 6 months on testosterone therapy
used as a reference point)
Digital Rectal Examination
(DRE)
5
PSA
The Diagnostic Triad
in Prostate Cancer
Digital Rectal Examination
• For patients with a PSA over 4 ng/ml
(n=9,776)
•
•
•
•
Normal DRE, Normal TRUS: PPV 17%
Normal DRE, Abnormal TRUS: PPV 33%
Abnormal DRE, Normal TRUS: PPV 32%
Abnormal DRE, Abnormal TRUS: PPV 75%
• Rietbergen et al, J Urol, 1999
• For patients with a PSA less than
4ng/ml
• DRE is of no value
• Schroeder et al, JNCI 1999
Prostate Specific Antigen
(PSA)
Age specific PSA levels
AGE
PSA LEVEL
40-50 Years
0-2.5ng/ml
50-60 Years
0-3.5ng/ml
60-70 Years
0-4.5ng/ml
70-80 Years
0-6.5ng/ml
Oesterling et al 1993
Kalish et al 1994
Transrectal Ultrasound
(TRUS)
TRUS
Cheap, but operator dependent
Examines the prostate in different planes, but only
on the basis of one section at any time.
uses a spatially flexible and variable twodimensional imaging technique, to visualise a
three-dimensional (3-D) anatomy and disease
process
The capsule, strictly speaking is not visible, and the
diagnosis of extracapsular involvement relies on
disruption of the periprostatic fat
Diagnostic triad for early detection
of prostate cancer
Trans-Rectal-Ultra-Sound Biopsy
T1: non palpable not visible laesion
T1a: < 5%
T1b: > 5%
T1c: tumor identified by biopsy (elevated
PSA)
T2: limited to the prostate
T2a: halve a lobe or less
T2b: more than halve a lobe but
only unilaterally
T2c: both lobes
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Staging Prostate Cancer
Problems: TRUS Bx
•
Important cancers are
missed
•
Clinically insignificant
cancers are identified by
chance
•
36-46% undergrading of
Gleason score
Imaging with Multi-parametric
MRI
Learning Objectives
1. High resolution T2-w: anatomy
2. Diffusion Weighted Imaging: function
3. Dynamic Contrast Enhanced: function
4. Hydrogen MR-Spectroscopy: function
MP-MRI: Learning
anatomy
Objectives
1 mm
MR-anatomy of PCa
Low SI: PCa
MR-anatomy of PCa
B
B
H
H
Low SI: PCa + hematoma + prostatitis + BPH
Multi-modality MRI: DWI
Organised galandular tissue
Tightly packed cellular tissue
DWI: PCa restricted H2O movement
Specificity, aggression!
Multi-modality MRI: DCE
DCE MRI: PCa increased vascular permeability
Sensitivity!
MR Spectroscopy
Metabolite ratios
Cho + Cr
Cit
Cho
Cr
Citrate
0.37 / 0.64
Multiparametric magnetic resonance images of
the prostate at 3 T
van Leeuwen, Eur Urol 5 9 ( 2 0 1 1 )
Prostate Cancer Biomarkers
33
CRITERIA IDEAL BIOMARKER FOR PCa…PSA
 Produced only by tumor tissue
 Non-invasive – easy to manage
 As inexpensive as possible to encourage widespread use
 Ability to detect PCa at an early stage
 Ability to differentiate aggressive tumors leading to death
 High specificity
 High sensitivity
34
PROMISING PCa BIOMARKERS IN THE FIELD
 PCA3 (Prostate CAncer gene 3)
 TMPRSS2-ERG (Transmembrane Protease, Serine)
 CTCs (Circulating Tumor Cells)
35
Is the PCA3 test the future?
Cells in prostatic
urethra
Digital Rectal
Exam (DRE)
PCA3
 Non coding messenger RNA
 Prostate cancer specific urine test
 Median 66x more PCA3 mRNA in prostate tumour cells
 PCA3 score = [PCA3 mRNA]/[PSA mRNA] x 1000
 Cutoff score 35
 Sensitivity 47-69%
Specificity 72-79%
 PSA 4,0-10,0:
Specificity 25-40%
37
Conclusions:
• PCA3 clinical performance was
validated in the largest repeat
biopsy study to date.
• Use of PCA3 in combination
with serum prostate specific
antigen and other risk factors
significantly increased diagnostic
accuracy.
Aubin, J Urol 10
PCA3 UPDATE
 PCA3 to aid in the decision to take initial biopsies. 1
 PCA3 correlated with tumour volume and insignificant PCa.2,3
 PCA3 does not correlate with ECE or SVI.3
 PCA3 no independent risk factor for aggressive disease.
1. De la Taille et al. Clinical evaluation of the PCA3 assay in guiding initial biopsy decisions. J Urol 2011.
2. Ploussard et al. Prostate cancer antigen 3 score accurately predicts tumour volume and might help in selecting prostate cancer
patients for active surveillance. Eur Urol 2011.
3. Auprich et al. Critical assessment of preoperative urinary prostate cancer antigen 3 on the accuracy of prostate cancer staging.
Eur Urol 2011.
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TMPRSS2-ERG
 Gene-rearrangement (fusion of TMPRSS2 and ETS)
 Non-invasive urine-test
 In ± 50% of PCa patients
 Sensitivity 32-51%
 Specificity 91-94%
 Association with cancer aggressiveness??
Demichelis F, Fall K, Perner S, et al. TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort. Oncogene 2007;26:4596-9.
Attard G, Clark J, Ambroisine L, et al. Duplication of the fusion of TMPRSS2 to ERG sequences identifies fatal human prostate cancer. Oncogene 2008;27:253-63.
FitzGerald LM, Agalliu I, Johnson K, et al. Association of TMPRSS2-ERG gene fusion with clinical characteristics and outcomes: results from a population-based
study of prostate cancer. BMC Cancer 2008;8:230.
Hessels D, Smit FP, Verhaegh GW et al. Detection of TMPRSS2-ERG fusion transcripts and prostate cancer antigen 3 in urinary sediments may improve diagnosis
40
of prostate cancer. Clin Can Res. 2007; 13: 5103-8.
CIRCULATING TUMOR CELLS (CTCs)
“Cancer cell that has detached from a solid tumor lesion
and entered the peripheral blood circulation”
Tumor
metastatic
spread of
cancer cells
Death..
41
A needle in a haystack
But what kind of needle?