Clinical Studies Summary
Prostate HistoScanning™
A tissue characterisation technology
supporting prostate cancer care
Introduction
•• HistoScanning™ is a new non-invasive tissue characterisation technology based on ultrasonography. It consists of a computeraided analysis of native ultrasound radiofrequency volume data to identify patterns in glandular tissue in order to detect
differentiated tissue.
•• Prostate HistoScanning™ is the commercially available transrectal ultrasound-based product of HistoScanning™, specifically
conceived to detect suspicious areas in the prostate. Because of its unique ability to accurately identify, locate and assess
the size of differentiated prostate tissue, Prostate HistoScanning™ may guide clinical decisions throughout entire prostate
cancer care: detection and diagnosis, treatment planning, treatment guidance and post-treatment monitoring (Figure 1).
•• To date over 1,500 patients have been enrolled in clinical studies on Prostate HistoScanning™ and more than 16,000 patients
have benefited already from it in clinical practice.
Tissue Characterisation with Prostate HistoScanning™
Detection and
Diagnosis
Treatment
planning
Treatment
guidance
Surveillance
FIGURE 1.
Tissue Characterisation with Prostate HistoScanning™
Detection and
Diagnosis
Treatment
Treatment
Surveillance
Visual Reassurance
for Decision Making
and True Targeting
planning
guidance
Detection and diagnosis
•• Prostate HistoScanning™ is often used in clinical practice
to determine the need for prostate biopsy and aid in
biopsy planning.
•• The ability of Prostate HistoScanning™ to predict biopsy
outcome has been evaluated in several clinical studies.1-6
% men with ≥ 1 positive
biopsy core
100
Determining biopsy need and
predicting biopsy outcome
•• In 2 single-centre pilot studies, 42-50 men with an
First biopsy
Repeat biopsy
80
75%
60
If THV < 0.20 mL,
40 0% of men had
50%
Prostate HistoScanning™ and thereafter had a first or
repeat biopsy.1,2
60%
a positive biopsy
20
0
< 0.20
0.20-0.49
0.50-0.99
≥ 1.00
THV (mL)
elevated prostate-specific antigen (PSA) level and/or
suspicious digital rectal examination (DRE) underwent
54%
81% 83%
FIGURE 3. The higher the median total cancer volume as
determined by Prostate HistoScanning™ (THV) the higher the
probability of a positive biopsy.1,2
•• Men with a positive first or repeat biopsy had a
statistically significantly larger median total cancer
biopsy (maximum 9 cores) in suspicious areas based on
volume as determined by Prostate HistoScanning™ (Total
Prostate HistoScanning™.7
HistoScanning Volume [THV]) compared to men with a
•• Prostate cancer was detected in 28 of 80 men (35%).
negative biopsy (Figure 2).
•• A total of 79% of all cancers were detected via the
14-core transrectal biopsy (Figure 4). Despite using a
maximum of only 9 cores, the transperineal Prostate
HistoScanning™-targeted biopsy detected 82% of all
cancers.
1.79
1.5
1
P<0.0001
0.71
0.5
0
0.10
0.30
Negative
(N=19)
≥ 1 positive core
(N=23)
Negative
(N=32)
Initial biopsy
≥ 1 positive core
(N=18)
Repeat biopsy
FIGURE 2. The median total cancer volume as determined by
Prostate HistoScanning™ (THV) is statistically significantly higher
in case of a positive biopsy vs. a negative biopsy.1,2
•• A higher median THV corresponded with a higher
percentage of men having a positive biopsy (Figure 3).1,2
% of all detected
prostate cancers (N=28)
Median THV (mL)
2
P=0.0007
100
80
60
79%
82%
14 cores
Max
9 cores
40
20
0
Systematic
transrectal biopsy
Transperineal
HistoScanning™targeted biopsy
FIGURE 4. Transperineal Prostate HistoScanning™ cognitivetargeted biopsy achieves similar prostate cancer detection rates
as systematic transrectal biopsy while reducing the number of
cores needed.7
In case of a median THV < 0.20 mL, no positive biopsies
were observed.
•• The cognitive targeted biopsy using Prostate
HistoScanning™ by the transperineal approach thus
Targeting biopsies
resulted in similar prostate cancer detection rates as the
•• Prostate HistoScanning™ may not only predict biopsy
outcome but also aid in targeting biopsies by indicating
suspicious areas in the prostate.
7,8
14-core systematic transrectal biopsy while reducing the
number of cores.
•• By reducing the number of cores needed, Prostate
•• A study was performed in 80 men who underwent
HistoScanning™ may aid in decreasing local tissue
a systematic 14-core transrectal biopsy which was
trauma and complications, patients’ pain and discomfort
supplemented with a cognitive targeted transperineal
and the surgical effort.
Clinical results of Prostate HistoScanning™
Treatment planning
•• Knowledge of the location and size of tumours may be
To provide direct instead of cognitive guidance in
transrectal ultrasound-based biopsy, the Prostate
HistoScanning™ TT system has been developed with
the ability to aid in biopsy needle orientation and
continuously monitor and document the planned
prostate biopsy. Prostate HistoScanning™ TT
complements Tissue Characterisation with True
Targeting functionality.
useful for treatment planning of a nerve-sparing radical
prostatectomy.
•• A retrospective study in 80 patients who had undergone
Prostate HistoScanning™ and radical prostatectomy
assessed whether Prostate HistoScanning™ could predict
a negative surgical margin.12
•• It was shown that when no Prostate HistoScanning™
For the definition and functionality of Prostate
volume or a volume < 0.20 mL was found at the left or
HistoScanning™ TT and True Targeting, refer to product
right side of the prostate, the probability of a negative
documentation MK2U00146D-EN.
surgical margin at that side was 91%.
•• On multivariate analysis, the presence of a Prostate
HistoScanning™ focus volume ≥ 0.20 mL was associated
Detecting significant cancer
with a 3.7-fold increased risk of a positive surgical margin
•• Prostate HistoScanning™ has also been evaluated for its
(P=0.027; Figure 5).
use to discriminate between clinically insignificant and
significant prostate cancer.9-12
•• A study in 32 men demonstrated that Prostate
HistoScanning™ outcomes were statistically significantly
different between pT2 and pT3 and between
Gleason sum ≤ 6, 7 and ≥ 7 cancers.
9
•• Another single-centre study in a smaller population
comparing Prostate HistoScanning™ results with radical
prostatectomy specimens showed that the likelihood
(calculated as relative risk) of Prostate HistoScanning™
to accurately grade tumours as Gleason grade 4/5 vs.
3 was 3.2 (P<0.0001).10
•• Furthermore, a study in 85 men undergoing radical
prostatectomy demonstrated that the sensitivity of Prostate
HistoScanning™ focus
≥ 0.20 mL vs. < 0.20 mL
3.66 P=0.027
HistoScanning™ focus
≥ 0.50 mL vs. < 0.20 mL
3.84 P=0.012
Biopsy Gleason sum 4
vs. negative biopsy
3.88 P=0.005
0
1
2
3
4
5
6
Odds ratio for presence of positive surgical margin
at radical prostatectomy
FIGURE 5. The risk of a positive surgical margin increases
almost 4-fold in case of a Prostate HistoScanning™-detected
focus ≥ 0.20 mL.12
HistoScanning™ in detecting prostate cancer increases
with tumour stage, grade and volume (Table 1).11
•• In another study in 25 men (50 prostate lobes) scheduled
for nerve-sparing radical prostatectomy, the use of
TABLE 1. Sensitivity of Prostate HistoScanning™ increases
with higher pathological stage, grade and volume of prostate
cancer.11
Prostate HistoScanning™ in addition to standard preoperative clinical assessment and 3 T diffusion-weighted
(DW) magnetic resonance imaging (MRI) changed the
nerve-sparing approach in 32% of lobes.13 A trend for
pT2 (N=44)
pT3 (N=38)
All (N=85)
reduced use of intra-fascial and extra-fascial nerve-
61%
92%
74%
sparing, and increased use of side excision was apparent
Gleason sum 6
(N=9)
Gleason sum 7
(N=50)
Gleason sum ≥ 8
(N=18)
55%
74%
83%
Tumour volume
< 1 mL (N=10)
Tumour volume
1-5 mL (N=40)
Tumour volume
> 5 mL (N=35)
50%
58%
86%
after refined staging with Prostate HistoScanning™. This
was reflected in reduced positive margin rates.
•• These studies suggest that Prostate HistoScanning™ may
refine and optimise pre-operative staging resulting in an
oncologically safer nerve-sparing radical prostatectomy
and reduced positive margin rates.
Treatment guidance
Post-treatment monitoring
•• Because of its ability to characterise prostate tissue,
•• The ability of Prostate HistoScanning™ to accurately
Prostate HistoScanning™ may aid in guiding local
localise cancer foci enables its use for monitoring
prostate cancer therapy, such as brachytherapy.
patients for recurrent disease after prior prostate cancer
•• A prospective, single-centre, phase II study has explored
therapy.15,16
the feasibility of selectively escalating the dose in tumour
•• A study in 90 patients who had been previously treated
areas inside the prostate by image-guided interstitial pulse-
with high-intensity focused ultrasound (HIFU) for localised
dosed rate (PDR)/high-dose rate (HDR) brachytherapy,
prostate cancer used Prostate HistoScanning™ to identify
i.e. fine-tuned dose-painting that allows the creation of
suspicious areas after 1-7 years. All patients underwent
microboost volumes.
biopsy for histological verification.15
14
Prostate HistoScanning™ was
performed to detect high-risk areas.
•• Prostate HistoScanning™ demonstrated a high diagnostic
•• Table 2 presents the interim results of 19 patients.
performance in detecting recurrent cancer foci of
> 0.20 mL after prior HIFU therapy (Table 3).
TABLE 2. Feasibility of Prostate HistoScanning™ in determining
brachytherapy areas.14
Dosimetric
quantifier (N=19)
Prostate
Median V100
99%
Median D90
112%
Prostate HistoScanning™
defined high-risk areas
TABLE 3. Diagnostic performance* of Prostate HistoScanning™
in detecting recurrent cancer foci > 0.20 mL after prior HIFU
therapy.15
Volume of suspicious area
124%
Median V120
94%
Median V130
85%
Dx: dose that covers x% of the prostate volume; Vx: fractional
volume of the prostate that received x% of the prescription dose.
< 0.20 mL
(N=51)
0.20-0.50 mL
(N=24)
> 0.50 mL
(N=15)
Sensitivity
100%
96%
100%
Specificity
8%
88%
100%
* Reference test biopsy
•• A good tolerability without significant acute side effects
(no grade ≥ 3 toxicities) was shown during 3-months
follow-up.
•• This suggests that Prostate HistoScanning™ cognitive
guidance for brachytherapy allows significant dose
escalations as microboost to prostate tumour regions
while meeting stringent dose constraints for the adjacent
organs at risk.
Conclusions
Prostate HistoScanning™ can provide support to clinicians to make informed decisions
throughout prostate cancer treatment to provide optimal patient care:
• determining the need for biopsy
• prediction of biopsy outcome and improved targeting of biopsies
• guidance in treatment planning and execution
• aid in monitoring of patients after treatment
The technology
Clinical validation
•• Prostate HistoScanning™ is a tissue characterisation
•• Several studies have validated the ability of Prostate
technology using native radiofrequency data from
HistoScanning™ to identify and characterise cancer
transrectal ultrasound (TRUS) volume scans of
foci with histology results from radical prostatectomy
the prostate. The native radiofrequency data are
specimens as reference test.9,19-29
analysed by a set of validated, multiparametric
•• The exploratory, open-label, proof-of-concept study
mathematical algorithms to detect specific changes
PHS -01 demonstrated that the concordance in
in tissue characteristics. This results in a 3-dimensional
diameter of index tumour was high between Prostate
prostate image in which suspicious areas in the
HistoScanning™ and histology results (r=0.95,
prostate are labelled in colour, superimposed on
P<0.001).19 Moreover, there was a 100% concordance
top of the simultaneously processed grey-scale TRUS
in attribution of multifocality and laterality. Prostate
image (Figure 6). A special volumetric tool enables
HistoScanning™ performed well in detecting cancer
measurement of total prostate volume and volume of
foci ≥ 0.50 mL on histology (Table 4).20 There was a
suspicious areas.
strong correlation in lesion volumes (r=0.99, P<0.001)
•• Prostate HistoScanning™ can be easily integrated in the
and total cancer volume (r=0.98, P<0.001) between
existing clinical pathway and has a short acquisition
Prostate HistoScanning™ and radical prostatectomy
and analysis procedure. Inter-observer agreement for
histology.
presence or absence of cancer foci ≥ 0.50 mL in prostate
sextants has been reported to be high (75%‑90%).17,18
TABLE 4. Diagnostic performance* of Prostate HistoScanning™
in predicting lesions ≥ 0.50 mL in 13 patients with 28 lesions
(12 lesions ≥ 0.50 mL).20
Volume
threshold
a.
Foci ≥ 0.50 mL
Sensitivity Specificity
100%
(12/12)
81%
(13/16)
PPV
NPV
80%
(12/15)
100%
(13/13)
PPV: positive predictive value; NPV: negative predictive value
* Reference test radical prostatectomy
•• The multi-centre, European, prospective cohort study
PHS-02 in patients with organ-confined prostate cancer
b.
c.
scheduled for radical prostatectomy examined the
diagnostic accuracy of Prostate HistoScanning™ to
locate a cancer focus of at least 0.20 mL or 0.50 mL
in a sextant.21 Prostate HistoScanning™ showed 90%
sensitivity and 70%‑72% specificity for the correct
localisation and identification of lesions ≥ 0.20 mL
and ≥ 0.50 mL within a sextant compared with radical
prostatectomy histology (Table 5).
FIGURE 6. a. Example slice of a surgical specimen case CLI-001
b. View of grid analysis of the example slice case CLI-001
c. View in Prostate HistoScanning™ of the example slice case
CLI-001
Image courtesy of Prof. Dr. František Zát’ura, Univerzita Palackého v Olomouci
(UPOL) - Urologická klinika - Fakultní nemocnice, Czech Republic.
TABLE 5. Diagnostic performance* of Prostate HistoScanning™
to correctly identify prostate cancer in 23 patients (138 sextants)
with an index foci ≥ 0.50 mL and 27 patients (162 sextants) with
an index foci ≥ 0.20 mL.21
Volume
threshold
Sensitivity Specificity
PPV
NPV
Foci ≥ 0.50 mL
90%
(79/88)
70%
(35/50)
84%
(79/94)
80%
(35/44)
Foci ≥ 0.20 mL
90%
(87/97)
72%
(47/65)
83%
(87/105)
82%
(47/57)
PPV: positive predictive value; NPV: negative predictive value
* Reference test radical prostatectomy
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