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Objective This study aimed to develop a preclinical model of prostate cancer (CaP) for studying focal/hemiablation of the prostate (IDEAL stage 0), and to use the information from the stage 0 investigation to design a novel focal surgical treatment approach—the precision prostatectomy (IDEAL stage 1/2a). Methods The IDEAL stage 0 study included simulation of focal/hemiablation in whole-mount prostate specimens obtained from 100 men who had undergone radical prostatectomies, but met the criteria for focal/hemiablation. The IDEAL stage 1/2a was a prospective, single-arm, Institutional Review Board-approved study of precision prostatectomy undertaken in eight men, who met the predetermined criteria. Criteria for both stages included (1) prostate-specific antigen (PSA) ≤15 ng/mL, (2) stage ≤cT2, (3) dominant unilateral lesion with Gleason ≤4+3 with any number of cores or % cores involved ipsilaterally on transrectal biopsy, (4) no primary Gleason ≥4 contralaterally on transrectal biopsy, and (5) preoperative erectile function score (International Index of Erectile Function (IIEF)-5) of ≥17 (out of 25) without PDE-5i (applicable only to the stage 1/2a study participants). Feasibility and safety of the precision prostatectomy technique, and short-term urinary, sexual and oncological outcomes were studied. Results Analysis of whole-mount specimens in the 100 men showed an index lesion (>1 cm in diameter) in all. Ninety-eight men had satellite lesions smaller than 0.5 cm∧3 in volume—46 on the side of the dominant lesions and 52 in the contralateral lobe. If the men in this modeling cohort had undergone focal ablation with a 5–10 mm untreated margin, all except one would have had at least Gleason 6 residual cancer. If they had undergone hemiablation with no untreated tissue on the ablated side, 56 men would have had residual cancer on the contralateral side, of whom 21 would have had clinically significant cancer (Gleason 7 or higher). If these men had undergone precision prostatectomy, with preservation of 5–10 mm of tissue on the non-dominant side, 10% and 4% would have had Gleason 3+4 and Gleason 4+3 disease left behind, respectively. For the stage 1/2a study, the median (IQR) age, PSA and IIEF-5 scores at the time of surgery were 54 (52–57) years, 4.4 (3.8–6.1) ng/mL and 24 (23-25), respectively. All eight patients were continent and sexually active at 12 months with a median IIEF-5 score of 21 (out of 25). At 24–30 months from surgery, the median PSA was 0.2 (range 0.1–0.7) ng/mL. Six men had undergone follow-up protocol biopsies, two, with undetectable PSA, had refused. Two men had residual Gleason 3+3 cancer, with PSA of 0.7 and 0.4 ng/mL, and remain on active surveillance. No man has undergone secondary whole-gland therapy. Conclusions Examination of whole-mount radical prostatectomy specimens in men who fit the conventional criteria of focal/hemiablation showed that approximately 21%–68% of men would have clinically significant CaP in the untreated tissue. In a small development cohort, precision prostatectomy was technically feasible, with excellent postoperative functional recovery. At 30 months of follow-up, no patient had clinically significant residual cancer or required secondary treatment. Pending long-term follow-up, a risk-stratified surgical approach may avoid whole-gland therapy and preserve erectile function in the majority of men with intermediate-risk CaP.
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SoodA, etal. BMJ Surg Interv Health Technologies 2019;1:e000002. doi:10.1136/bmjsit-2019-000002
Open access
The Precision Prostatectomy: an IDEAL
Stage 0, 1 and 2a Study
Akshay Sood, 1 Wooju Jeong,1 Kanika Taneja,2 Firas Abdollah,1
Isaac Palma-Zamora,1 Sohrab Arora,1 Nilesh Gupta,2 Mani Menon1
To cite: SoodA, JeongW,
TanejaK, etal. The Precision
Prostatectomy: an IDEAL Stage
0, 1 and 2a Study. BMJ Surg
Interv Health Technologies
2019;1:e000002. doi:10.1136/
bmjsit-2019-000002
Received 18 March 2019
Revised 17 July 2019
Accepted 17 July 2019
1Vattikuti Urology Institute,
Henry Ford Hospital, Detroit,
Michigan, USA
2Department of Pathology, Henry
Ford Hospital, Detroit, Michigan,
USA
Correspondence to
Dr Akshay Sood;
asood1@ hfhs. org
Original article
http:// dx. doi. org/ 10. 1136/
bmjsit- 2019- 000015
© Author(s) (or their
employer(s)) 2019. Re-use
permitted under CC BY-NC. No
commercial re-use. See rights
and permissions. Published by
BMJ.
Key messages
What is already known about this subject?
Whole-gland treatment of prostate cancer (CaP) of-
ten leads to unintended adverse functional effects,
in particular, sexual impotence.
Focal ablative techniques for treatment of local-
ized CaP have recently emerged to avoid such
functional decline; although these focal ablative
techniques have shown promise, a few limitations
have emerged: (1) an inability or reluctance to treat
a prostate gland >40 gm, (2) an inability to ablate
>60% of the whole gland, (3) lack of pathological
information, and (4) a high positive biopsy rate in the
residual prostate tissue resulting in a high rate of
redo procedures (~25% of the patients).
What are the new ndings?
Precision prostatectomy allows for removal of great-
er than 90% of the prostate with complete removal
of the side of the dominant lesion, and removal of
the majority of satellite lesions on the contralateral
side.
All eight patients who underwent precision pros-
tatectomy in this exploratory study were continent
and potent within 12 months from surgery, and no
patient (out of eight) had clinically signicant resid-
ual cancer or required secondary treatment at a fol-
low-up of 30 months.
How might it impact on clinical practice in the
foreseeable future?
Precision prostatectomy may allow patients to
choose a risk-stratied surgical approach to treat-
ment of localized CaP.
ABSTRACT
Objective This study aimed to develop a preclinical model
of prostate cancer (CaP) for studying focal/hemiablation
of the prostate (IDEAL stage 0), and to use the information
from the stage 0 investigation to design a novel focal
surgical treatment approach—the precision prostatectomy
(IDEAL stage 1/2a).
Methods The IDEAL stage 0 study included simulation
of focal/hemiablation in whole-mount prostate
specimens obtained from 100 men who had undergone
radical prostatectomies, but met the criteria for focal/
hemiablation. The IDEAL stage 1/2a was a prospective,
single-arm, Institutional Review Board-approved study of
precision prostatectomy undertaken in eight men, who
met the predetermined criteria. Criteria for both stages
included (1) prostate-specic antigen (PSA) ≤15 ng/
mL, (2) stage ≤cT2, (3) dominant unilateral lesion with
Gleason ≤4+3 with any number of cores or % cores
involved ipsilaterally on transrectal biopsy, (4) no primary
Gleason ≥4 contralaterally on transrectal biopsy, and (5)
preoperative erectile function score (International Index of
Erectile Function (IIEF)-5) of ≥17 (out of 25) without PDE-
5i (applicable only to the stage 1/2a study participants).
Feasibility and safety of the precision prostatectomy
technique, and short-term urinary, sexual and oncological
outcomes were studied.
Results Analysis of whole-mount specimens in the
100 men showed an index lesion (>1 cm in diameter) in
all. Ninety-eight men had satellite lesions smaller than
0.5 cm3 in volume—46 on the side of the dominant
lesions and 52 in the contralateral lobe. If the men in this
modeling cohort had undergone focal ablation with a
5–10 mm untreated margin, all except one would have had
at least Gleason 6 residual cancer. If they had undergone
hemiablation with no untreated tissue on the ablated
side, 56 men would have had residual cancer on the
contralateral side, of whom 21 would have had clinically
signicant cancer (Gleason 7 or higher). If these men had
undergone precision prostatectomy, with preservation
of 5–10 mm of tissue on the non-dominant side, 10%
and 4% would have had Gleason 3+4 and Gleason 4+3
disease left behind, respectively. For the stage 1/2a study,
the median (IQR) age, PSA and IIEF-5 scores at the time of
surgery were 54 (52–57) years, 4.4 (3.8–6.1) ng/mL and
24 (23-25), respectively. All eight patients were continent
and sexually active at 12 months with a median IIEF-5
score of 21 (out of 25). At 24–30 months from surgery,
the median PSA was 0.2 (range 0.1–0.7) ng/mL. Six men
had undergone follow-up protocol biopsies, two, with
undetectable PSA, had refused. Two men had residual
Gleason 3+3 cancer, with PSA of 0.7 and 0.4 ng/mL, and
remain on active surveillance. No man has undergone
secondary whole-gland therapy.
Conclusions Examination of whole-mount radical
prostatectomy specimens in men who t the conventional
criteria of focal/hemiablation showed that approximately
21%–68% of men would have clinically signicant CaP
in the untreated tissue. In a small development cohort,
precision prostatectomy was technically feasible, with
excellent postoperative functional recovery. At 30 months
of follow-up, no patient had clinically signicant residual
cancer or required secondary treatment. Pending long-
term follow-up, a risk-stratied surgical approach may
avoid whole-gland therapy and preserve erectile function
in the majority of men with intermediate-risk CaP.
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Open access
INTRODUCTION
Whole-gland treatment of localized prostate cancer (CaP)
is associated with a substantial risk of adverse outcomes,
in particular of erectile dysfunction.1 2 In an attempt to
minimize this, a few investigators have developed tech-
niques of focal CaP ablation, following the well-estab-
lished organ-preserving treatment paradigms in other
malignancies.3–6 While several techniques have been
described,7 the underlying premise is to treat the index
lesion,8 9 where visible on imaging (with focal therapy),
or one side of the prostate, when lesions are not visible
(hemiablation).
Clinical studies of focal therapy in CaP, notably of high-in-
tensity focused ultrasound (HIFU), have shown promise—
1-year continence and potency rates have been reported
to be 100% and 89%, respectively,10 11 and 5-year metasta-
sis-free and cancer-specific survival rates were reported to
be 98% and 100%, respectively, in a recent multi-institu-
tional study of HIFU.12 However, certain limitations have
emerged: an inability or reluctance to treat a prostate gland
>40 g, (2) an inability to ablate >60% of the whole gland, (3)
lack of pathological information on the ablated prostatic
tissue, and (4) a high positive biopsy rate in the residual
prostate tissue resulting in a high rate of redo procedures
(~25% of the patients) at 3 years.13
We undertook a preclinical study to model the oncolog-
ical outcomes of focal/hemiablation in a cohort of men
who had undergone whole-gland radical prostatectomy
for localized CaP, but met the criteria for focal/hemiab-
lation (IDEAL stage 0). We used these data to develop a
technique that would optimize the maintenance of erec-
tile function, while allowing for the maximal removal of
CaP, including the index and most/all satellite lesions
(IDEAL stage 1/2a). Our primary intent was the precise
preservation of erectogenic nerves, hence the term
precision prostatectomy. These studies follow the IDEAL
framework for safe surgical innovation14–16 where preclin-
ical studies are considered stage 0, and the first stage of
innovation, performed on a handful of carefully selected
patients, stage 1/2a.
METHODS
IDEAL stage 0: conceptualization of the technique and
preclinical simulation
We retrospectively analyzed 100 consecutive whole-mount
radical prostatectomy specimens from patients that had
undergone robotic radical prostatectomy (January 2016–
January 2017) and satisfied the following criteria: (1)
prostate-specific antigen (PSA) 15 ng/mL, (2) stage
cT2, (3) dominant unilateral lesion with Gleason score
4+3 with any number of cores or % cores involved ipsilat-
erally on transrectal ultrasound (TRUS) prostate biopsy,
and (4) no primary Gleason score 4 contralaterally on
TRUS prostate biopsy; these inclusion criteria were based
on prior focal therapy studies.10 17 In the IDEAL stage 0
part of the study, we examined the whole-mount radical
prostatectomy specimens, to
1. Map the CaP lesions, including grade and tumor
diameter.
2. Determine the distribution of lesions that were below
the size limit of mp-MRI detection, usually defined as
10 mm in diameter or 0.5 cm3.18
3. Simulate a “what if” scenario to examine residual can-
cer rates, if these men were treated with focal or hemia-
blation rather than with conventional prostatectomy.
4. Use the risk estimates generated in this stage to devel-
op a novel technique—the precision prostatectomy—
that removes the entire hemi prostate and seminal
vesicle complex on the side of the index lesion, but
leaves a thin rim of prostatic capsule (5–10 mm) on the
side contralateral to the dominant lesion.
IDEAL stage 1/2a: study population, informed consent and
surgical technique
We examined the feasibility of precision prostatectomy
in eight carefully selected men who were desirous of
focal therapy to the prostate (IDEAL stage 1/2a). These
men were evaluated and treated over a 6-month period,
between January and July 2017, allowing a minimum
follow-up of 24 months. All men placed high priority
on preservation of erectile function and sought out the
treating surgeon specifically requesting focal therapy.
No man was a candidate for active surveillance, and all
met the following criteria: (1) PSA 15 ng/mL, (2) stage
cT2, (3) dominant unilateral lesion with Gleason score
4+3 with any number of cores or % cores involved ipsilat-
erally on TRUS prostate biopsy, (4) no primary Gleason
score 4 contralaterally on TRUS prostate biopsy, and
(5) preoperatively potent without phosphodiesterase
type 5 (PDE-5) inhibitors. Data collection was under an
ongoing protocol approved by the Institutional Review
Board, and in compliance with Health Insurance Porta-
bility and Accountability Act of 1996 (HIPAA) regula-
tions. Informed consent was obtained from all patients.
The patients were apprised of the experimental nature
of the procedure, and the fact that the risks could not
be accurately estimated given the novelty of the proce-
dure. Patients were required to review the informational
material for at least 7 days before they were considered
for precision prostatectomy. Failing this in-home eval-
uation, patients were assigned to conventional radical
prostatectomy.
Patient positioning, port placement, developing the
space of Retzius and prostatic pedicle dissection followed
our standard anterior Vattikuti Urology Institute tech-
nique of prostatectomy.19 20 However, in the precision pros-
tatectomy, standard nerve-sparing radical prostatectomy
was undertaken on the side of the dominant lesion. On
the contralateral side, the dissection was started anterior
to the vas deferens/seminal vesicle complex, preserving
all layers of Denonvilliers' fascia, with the included erecto-
genic nerves.21 22 The dissection was continued 5–10 mm
into the prostatic capsule, deliberately attempting to
leave behind a thin rim of prostatic capsule (5–10 mm)
along with the seminal vesicle/ejaculatory duct complex.
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Open access
Systematic needle biopsies (via a suprapubic approach)
were taken from the remnant prostatic tissue, and sent
for frozen section analysis. Completion prostatectomy was
performed if the frozen biopsies showed residual cancer.
Vesicourethral anastomosis was performed as previously
described.19 20 The patients received a Foley or supra-
pubic tube per patient choice.
For the stage 1/2a study, our goals were to assess:
1. The safety and feasibility of the technique.
2. Continence and potency outcomes.
3. Short-term oncological control as assessed by bio-
chemical recurrence (using the American Urological
Association (AUA) definition of biochemical recur-
rence following radical prostatectomy or the ASTRO
criteria used for radiation or focal therapy) and proto-
col biopsies of residual tissue.
IDEAL stage 0 and 1/2a: variables, endpoints and denitions
For each patient (stage 1/2a), the following clinical
parameters were noted: age at surgery, body mass index,
comorbidities, American Society of Anesthesiologists
score, preoperative PSA, clinical tumor stage (cT), and
biopsy Gleason score, total number of cores on biopsy,
number of positive cores on biopsy and percentage core
positivity. Operative parameters collected included total
operative time, console operative time, estimated blood
loss, intraoperative complications and need to convert to
radical prostatectomy. Pathological parameters collected
included pathologic Gleason Score, pathological tumor
stage (pT) and surgical margin status (negative vs posi-
tive). The prostatectomy specimens were sectioned and
processed according to the previously described method-
ology by Ruijter et al.23 Briefly, after fixation and marking
of surgical planes with dye, radical prostatectomy speci-
mens were cut into serial parallel transverse 4 mm thick
slices. Following histological processing and complete
embedding, 4 µm tissue sections were stained with H&E.
All the tumor nodules were outlined in ink on the cover-
slips of all the slides. The whole tumor was mapped and
reconstructed, and the three-dimensional (3D) shape
and size of the tumor was determined. For calculating
the maximum dimension of tumor, apart from the largest
dimension on a single slide, the longitudinal contiguous
tumor dimension across sequential sections was also taken
into account. This dimension was calculated by multi-
plying the thickness of slice by the number of sections
in which tumor was present. Postoperative complica-
tions noted included need for blood transfusion, urinary
tract infections, lymphoceles, deep venous thrombosis
(DVT), pulmonary embolus (PE), pneumonia, myocar-
dial infections and death for 30 days after surgery. Preop-
erative and postoperative urinary and sexual function
assessments were performed using the International
Prostate Symptom Score (IPSS) and International Index
of Erectile Function (IIEF-5) questionnaires. Postopera-
tive PSA was collected at 4, 8 and 12 months postopera-
tively. Biochemical recurrence (BCR) was defined using
American Urological Association (AUA) criteria for
BCR following radical prostatectomy.24 All patients were
followed for at least 12 months.
Definitions: for stages 0 and 1/2a, unilateral disease
(preoperative) was defined as cancer limited to only one
side of the prostate on 12 or more cores of TRUS-guided
biopsy, while bilateral disease included both sides (the
same definition was utilized for whole-mount analysis). A
dominant lesion on biopsy was defined as the lesion with
the highest grade, and in case, two or more lesions had
the same Gleason score, the lesion with the greatest core
length positivity was designated as the dominant lesion.
A dominant nodule was the lesion with highest grade
on final pathology, and similar to the dominant lesion
on biopsy, if two or more nodules had the same Gleason
score, the larger nodule was designated as the domi-
nant nodule. Clinically significant cancer was defined as
a lesion with Gleason score 3+4, based on prior focal
therapy studies.10 11
Nomenclature: A focus group of 30 men, including
those in this report, were asked to come up with a name
for the procedure or to choose from a menu of options:
focal surgery, focal prostatectomy, subtotal prostatectomy,
precision surgery, precision prostatectomy or capsule
preserving prostatectomy. The consensus of the men
was precision prostatectomy (29/30 men), with term
“Menon” added on by patient request because a majority
wanted to assign the credit (or the blame) to the treating
surgeon (Menon precision prostatectomy (MPP)).
Statistical analyses
Descriptive statistics of categorical variables focused on
frequencies and proportions. Medians and (IQR) were
reported for continuously coded variables. Kaplan-Meier
estimates were constructed to assess 12-month urinary
continence and sexual potency rates. Statistical anal-
yses were performed using the R statistical package (R
Foundation for Statistical Computing, Vienna, Austria),
considering a statistical significance at two-sided p<0.05.
RESULTS
IDEAL stage 0: baseline characteristics
The median (IQR) age and PSA were 61 (58–66) years
and 5.1 (4.1–7.8) ng/mL, respectively, in the 100 patients
in the preclinical study. The clinical stage was cT1 in 79%
(n=79) of the patients, and cT2 in the remaining. The
biopsy Gleason was 3+3 in 21% (n=21), 3+4 in 53% (n=53)
and 4+3 in 26% (n=26). The median (IQR) number of
cores positive on biopsy were 4 (3–6). On transrectal
biopsies, 48 men had disease located to one half of the
prostate and 52 had bilateral disease.
IDEAL stage 0: whole-mount radical prostatectomy specimen
analysis, and MPP and focal HIFU simulation analysis
In prostate mapping studies of the whole-mount radical
prostatectomy specimens, 96% of the patients had cancers
involving at least a part the peripheral zone, defined as
within 5–10 mm of the prostatic capsule; the remaining
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Open access
Figure 1 Whole-mount analysis and mapping of cancer lesions within the prostate in 100 radical prostatectomy specimens
of patients that met criteria* for focal therapy but had undergone radical prostatectomy previously. *Inclusion criteria: (1)
prostate-specic antigen ≤15 ng/mL, (2) stage ≤cT2, (3) dominant unilateral lesion with Gleason score ≤4+3 with any number
of cores or % cores involved ipsilaterally on transrectal ultrasound (TRUS) prostate biopsy, and (4) no primary Gleason score
≥4 contralaterally on TRUS prostate biopsy; the yellow zone represents 5–10 mm margin of the prostatic peripheral zone and
prostatic capsule.
4% patients had anterior zone tumors only. Seventy-one
per cent (71%) of the men had clinically significant
disease (Gleason score 7) in the peripheral zone, within
5–10 mm of the prostatic capsule (figure 1).
In all 100 patients, a dominant nodule was identifiable.
Ninety-eight men had additional satellite lesions smaller
than 0.5 cc in volume—46 on the side of the dominant
lesions and 52 in the contralateral lobe. Seventy-two per
cent (72%) of the patients had bilateral disease on whole-
mount analysis (figure 1 provides further details).
If all 100 men in the modeling cohort had been
treated with focal ablation, all men except 1 would
have had residual Gleason 6 cancer. Further, only 25
patients would have qualified for focal therapy, given the
recommended prostate weight cut-off of 40 g for HIFU.
In these 25 men, 44% would have had residual Gleason
3+4, 16% Gleason 4+3, 4% Gleason 4+4% and 4%
Gleason 4+5 disease (figure 2), given that focal HIFU
spares 5–10 mm of peripheral tissue on the treatment
side and does not treat the contralateral side. Thus,
only 8 men of the original 100 would have been eligible
and completely treated in the modeling cohort. With
hemiablation, 44 men would have had complete cancer
ablation, 56 men would have had residual cancer and
21 would have clinically significant cancer (Gleason 7
or higher).
In the simulation analysis, if these men had under-
gone MPP with preservation of 5–10 mm of tissue on
the contralateral side, no patient of the 48 with unilat-
eral disease would have had clinically significant cancer
(Gleason 7) in the preserved tissue. If patients with
bilateral disease (n=52) had undergone MPP, 19.2%
would have had Gleason 3+4% and 7.6% Gleason 4+3
disease left behind (figure 3). Hence, overall in these 100
patients, 14% of the patients would have had clinically
significant (Gleason 3+4, n=10, Gleason 4+3, n=4) disease
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Figure 2 Simulation, pictorial representation and outcomes of focal HIFU in the whole-mount radical prostatectomy
specimens of patients eligible for focal therapy; n=25 patients (IDEAL stage 0 study). HIFU, high-intensity focused ultrasound.
left behind after simulated MPP, while 86% would have
avoided whole-gland therapy.
IDEAL stage 1/2a: baseline characteristics, modications to
technique and outcomes
Baseline characteristics are provided in table 1. Eight
patients underwent MPP. Median (IQR) age and PSA were
54 (52–57) years and 4.4 (3.8–6.1) ng/mL, respectively.
All patients were potent preoperatively with a median
IIEF-5 score of 24. The majority of the patients had cT1
disease, 62.5% (n=5). The biopsy Gleason score was 3+4
in 50% (n=4); the remaining 4 had 3+3 disease. The
median (IQR) number of cores positive on biopsy were
3.5 (2–5). Seventy-five (n=6) per cent of the patients had
unilateral disease on biopsy. None of the eight patients
met the Epstein criteria for active surveillance.25
Two surgeons (MM and WJ) were involved in the
procedure, with MM being the supervising surgeon in
all cases. Median (IQR) console time was 134 (108–148)
min. Hemostasis was accomplished with a cautery: no
hemostatic agents were used. There were no complica-
tions intraoperatively or postoperatively. None of the
procedures were converted to conventional radical pros-
tatectomy (table 2). One modification to technique was
made during the series: intraoperative ultrasound was
introduced after the first two cases, to measure the depth
of residual tissue left in situ. This was between 4 and
10 mm in all six men, confirming that the intent had been
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Open access
Figure 3 Simulation, pictorial representation and outcomes of precision prostatectomy in the whole-mount radical
prostatectomy specimens of patients eligible for focal therapy; n=100 patients (IDEAL stage 0 study). GS, Gleason score; TRUS,
transrectal ultrasound.
achieved. On final pathology, five men (62.5%) had pT2c
disease. No patient had a positive surgical margin on the
side of the radical prostatectomy, while two patients had a
positive margin at the site of precision prostatectomy, but
a negative frozen section of the capsular tissue. One of the
two patients with positive surgical margins on the spec-
imen site had Gleason 3+4 disease at the affected margin,
while the other had Gleason 3+3. Follow-up protocol
biopsy of the remnant tissue showed focal Gleason six
cancer in the former patient, and no cancer in the latter.
At 12 months from surgery, all patients had recovered
urinary continence and sexual potency. The median
(IQR) time to urinary continence was 1 (1–2.5) month
and for sexual potency was 4 (4–10) months, with seven
of the eight (87.5%) patients potent by 4 months. The
median (IQR) 12-month IPSS and IIEF-5 scores were 3
(2–4) and 21 (19–25), respectively. The median (IQR)
PSA was 0.2 (0.1–0.4) ng/mL at 12 months, and the PSAs
remained stable at 24–30 months of follow-up. Per the
AUA definition for biochemical recurrence following
radical prostatectomy, two of the eight (25%) patients had
biochemical recurrence within 12 months (table 2). None
(0%) of the patients would have been considered to have
a biochemical recurrence, per the ASTRO criteria.26 The
PSA values of the two patients with BCR (per the AUA
criteria) were 0.4 and 0.7 ng/mL at 12 months.
Two men with an undetectable PSA and excellent
functional outcomes declined protocol biopsies. Four
men had protocol biopsies in the absence of PSA recur-
rence, and none had evidence of cancer (median (range)
cores: 8 (8-15)). Two patients with PSA recurrence (one
with a positive and one with a negative surgical margin)
underwent prostate transrectal ultrasound-guided biopsy
at 12 months. Both patients had focal Gleason 3+3
cancer in the remnant and are on active surveillance.
All four patients without biochemical recurrence had a
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Open access
Table 1 Preoperative characteristics in patients undergoing
robot-assisted precision prostatectomy, n=8 (MPP; IDEAL
stage 1/2a)
PREOPERATIVE PARAMETERS
Demographic details
Age in years; median (IQR) 54 (52–57)
BMI in kg/m2; median (IQR) 29 (24.7–34.3)
Comorbidities; n (%)
Diabetes mellitus 2 (25)
Hypertension 1 (12.5)
COPD/Asthma 0 (0)
Cerebrovascular disease 2 (25)
Prior abdominal surgeries 0 (0)
American Society of Anesthesiologists
score; median (IQR)
2 (1–3)
Tumor characteristics
PSA in ng/mL; median (IQR) 4.4 (3.8–6.1)
Clinical tumor stage; n (%)
cT1 5 (62.5)
cT2a 3 (37.5)
Transrectal ultrasound-guided biopsy
(12–16 cores)
Highest Gleason score; n (%) 5 (62.5)
3+3 4 (50)
3+4 4 (50)
Number of positive cores; median
(IQR)
3.5 (2–5)
Percent core positivity; median (IQR) 29.2 (16.7–41.7)
Unilateral disease (core positivity
limited to one side); n (%)
6 (75)
Preoperative IIEF-5 score; median (IQR) 24 (23–25)
Preoperative IPSS score; median (IQR) 3 (2.5–3.5)
BMI, body mass index; COPD, chronic obstructive pulmonary
disease; IIEF-5, International Index of Erectile Function; IPSS,
International Prostate Symptom Score; IQR, IQR range; PSA,
prostate specic antigen.
Table 2 Operative and postoperative outcomes in patients
undergoing robot-assisted precision prostatectomy, n=8
(MPP; IDEAL stage 1/2a)
OPERATIVE OUTCOMES
Operative time (incision–closure) in minutes; median
(IQR)
173 (143–185)
Console time (console start–nish) in minutes;
median (IQR)
134 (108–148)
Patients with suprapubic tube at end of procedure;
n (%)
7 (87.5)
Estimated blood loss; median (IQR) 100 (85–200)
Volume of prostate tissue left behind in *cm3;
median (IQR)
4 (2–7)
Complications/adverse outcomes; n (%)
Intraoperative complications 0 (0)
Margin positivity of the remnant tissue on frozen
section analysis
0 (0)
Need for conversion to radical prostatectomy 0 (0)
POSTOPERATIVE OUTCOMES
Length of stay in days; median (IQR) 1 (1–1)
Postoperative complications**; n (%) 0 (0)
Hospital readmission in 30 days; n (%) 0 (0)
Pathological analysis; n (%)
Pathological tumor stage; n (%)
pT2a 3 (37.5)
pT2c 5 (62.5)
Highest Gleason score; n (%)
3+3 1 (12.5)
3+4 6 (75)
4+3 1 (12.5)
Lymph-node involvement; n (%) 0 (0)
Nerve sparing on the side of the dominant nodule;
n (%)
Veil 5 (62.5)
Standard 3 (37.5)
Surgical margin positivity; n (%)
On the side of the radical dissection 0 (0)
On the side of the precision prostatectomy 2 (25)
PSA at 12 months; median (IQR) 0.2 (0.1–0.4)
Patients with biochemical recurrence per AUA
denition; n (%)
2 (25)
Patients with biochemical recurrence per ASTRO
criteria; n (%)
0 (0)
Patients undergone additional therapy at latest
follow-up (24-30 months); n (%)
0 (0)
Urinary continent at 12 months; n (%) 8 (100)
Sexual health at 12 months; n (%)
Potent at 12 months*** 8 (100)
Using PDE-5 inhibitors 4 (50)
Using intracavernosal injections 0 (0)
*n=6 for this data point; **Postoperative complications included need
for blood transfusion, DVT/PE, lymphoceles, urinary tract infection or
cardiopulmonary events; ***Five out of the eight patients were potent
by 1 month (total=62.5%), an additional two were potent by 4 months
(total=87.5%), and all were potent by 12 months (100%).
AUA, American Urological Association; DVT, deep vein thrombosis; PE,
pulmonary embolism; PSA, prostate-specic antigen.
combination of benign prostatic tissue and fibromuscular
tissue on biopsies. No patient had required additional
therapy at their last follow-up (24–30 months).
DISCUSSION
Radical prostatectomy or radiation therapy are well-es-
tablished methods of treating CaP. A high rate of cancer
control is achieved, but at the cost of significant functional
effects, especially erectile dysfunction. Two contemporary
publications suggest that erectile dysfunction remains
problematic. Published data from well-designed prospec-
tive trials in the UK (ProtecT)27 and the USA (CAESAR)1
demonstrate erectile dysfunction rates of 50%–70% at 12
months after prostatectomy. A report from a single center
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Open access
of excellence in the USA, Memorial Sloan-Kettering
Cancer Center, is largely confirmatory (27% potency),
despite the use of intracavernosal injections, refinements
in nerve sparing, and adoption of robotics.2
The results are quite different in men undergoing
simple prostatectomy or prostate-sparing radical cystec-
tomy. Several series report a potency rate of about 90%.
This suggests that a key to preserving potency may lie in
preserving the “prostatic capsule”,28–30 where the network
of erectogenic nerves is located.21 22 In this regard, focal
HIFU, which spares at least 50% of the prostate,10–12
has shown promise. The seminal work by Ahmed and
colleagues reported a potency rate of 89% at 12 months
and a continence rate of 100%.10 Other studies on focal
therapy (HIFU and others) have corroborated their find-
ings.11 13 31
There remains a concern regarding the oncological
efficacy of the procedure, however. A multicenter 5-year
follow-up of 505 men with intermediate risk CaP who
underwent focal HIFU reported a cancer-specific survival
of 100%,12 but a retreatment rate of 27% and a positive
biopsy rate of 25% in men who were re-biopsied. Another
single-institution study of 150 men (n=132, Gleason 7)
showed residual cancer in 81% of men who underwent
confirmatory biopsy and a 25% retreatment rate, despite
an attempt to ablate fivefold to 10-fold the lesion volume
detected on mp-MRI.13
We reasoned that the high anatomical failure rate from
focal HIFU may be related to the presence of residual CaP
that is below the detection resolution of MRI, currently,
10 mm in diameter or 0.5 cm3 in volume. Our preclin-
ical, stage 0, prostatic mapping study was performed to
test the validity of this assumption. We found that >70%
of men who were candidates for focal or hemiablation
therapy harbored low volume clinically significant CaP
on analysis of whole-mount specimens. These results are
comparable with other reports. Kenigsberg et al in a simu-
lation study of focal HIFU in radical prostatectomy spec-
imens noted that significant cancer (Gleason pattern 4
or above) would have been left behind in 23.7% of the
patients who had underwent mp-MRI evaluation.32 Simi-
larly, Elkhoury et al demonstrated that detection rate
of Gleason 7 cancer via mp-MRI fusion biopsy varies
between 47% and 60% in patients with mp-MRI visible
lesions, while 15% of clinically significant cancers are
invisible.33
Our analysis allowed us to simulate a novel surgical
technique, precision prostatectomy. In this approach, we
attempt to remove all prostatic tissue, but for a 5–10 mm
rim of prostate capsule on the side contralateral to the
dominant lesion. In a “what-if” analysis, if all men had
undergone precision prostatectomy, the residual cancer
rate would have been 14% (10% Gleason 3+4, 4% Gleason
4+3) while it would have been 68% had they undergone
focal HIFU (44% Gleason 3+4, 16% Gleason 4+3, 4%
Gleason 4+4% and 4% Gleason 4+5; see figures 2 and
3). Looked at in another way, precision prostatectomy
would have spared 86% of men from having whole-gland
therapy, with equivalent oncologic control, and a higher
erectile function rate than whole-gland therapy. This is
probably due to the fact that precision prostatectomy
allows for removal of greater than 90% of the prostate
with complete removal of the side of the dominant lesion,
and removal of the majority of satellite lesions on the
contralateral side.
Following IDEAL guidelines, the stage 0 study was
followed by a stage 1/2a study of MPP in eight highly
selected patients. Precision prostatectomy offers several
conceptual benefits over focal/hemiablation. No patient
needed to be excluded because of prostate size or the
location of the tumor. It is noteworthy that manufac-
turers’ guidelines suggest limiting focal HIFU to men
with prostate volumes less than 40 cc, and to men without
apical/anterior tumors, approaching 75% of men in the
preclinical study. Further, the treated tissue remains avail-
able for detailed pathological or genomic analysis after
MPP, while it is destroyed at ablation.
In this development study, we demonstrate that MPP
is technically feasible and safe. No patient needed to be
converted to radical prostatectomy, or suffered an intra-
operative or postoperative complication. Only one modi-
fication to technique was made during this series: using
intraoperative ultrasonography with a drop-in probe, we
were able to measure accurately the volume of residual
tissue and confirm that the intent of removing >90% of
prostatic tissue was met.
From a functional outcomes standpoint, the patients
undergoing precision prostatectomy achieved excellent
results, with all eight (100%) patients achieving urinary
continence within 4 months of surgery and potency
within 12 months.
Evaluation of the oncological effectiveness of focal
therapy has been bedeviled by a lack of consensus on
what constitutes a PSA failure, an important surrogate for
oncological control after radical prostatectomy. After all,
a significant portion of the prostate is left behind after
focal therapy, and continues to produce PSA. Most inves-
tigators are silent about PSA values after focal therapy,
but Bass et al found that the PSA nadir was 2–3 ng/mL
at 2–3 years of follow-up.13 Using the AUA definition for
biochemical recurrence following radical prostatectomy
(PSA of 0.2 ng/mL and rising, or a single value of 0.4 ng/
mL24), we demonstrated that two out of the eight (25%)
patients developed biochemical recurrence, whereas no
patient (0%) had a recurrence if we used the ASTRO
criteria for recurrence.26 Postoperative biopsy in the two
patients with biochemical recurrence (per AUA criteria)
showed low-volume, low-risk disease: 1/6 cores of Gleason
3+3 in one patient and 2/6 cores of Gleason 3+3 in the
other.
Another important oncological consideration is the
evaluation of surgical margins. Information about surgical
margins cannot be obtained from ablation studies, where,
by definition, no tissue is removed. Further, the use of
surgical margins as a meaningful endpoint is debatable:
the recent 29-year follow-up of SPCG-4 trial,34 and our
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SoodA, etal. BMJ Surg Interv Health Technologies 2019;1:e000002. doi:10.1136/bmjsit-2019-000002
Open access
prior work,35 suggests that surgical margins matter mini-
mally, if at all, unless patients have extraprostatic disease
and high-grade cancer. In line with this, the two patients
that had positive surgical margins have not required addi-
tional treatment and remain on active surveillance with
stable PSAs.
Our study has several limitations. By design, this is
a stage 0-1/2a, single-center study evaluating a small
number of patients. Hence, conclusions should be drawn
with caution. However, the study design is in accordance
with recommendations provided by the IDEAL collabo-
ration for surgical innovation. A second limitation is that
MRIs were not performed in these men. The reasons for
this were partly pragmatic, and partly by intent. At the
time that the patients in the stage 0 study were operated
on, mp-MRI was not readily available for general clin-
ical use in the USA. And a raison d’etre for the study
was to examine the distribution of clinically significant
cancers that are smaller than the current detection limit
of mp-MRI in a target population that would qualify for
focal therapy.
Another limitation of precision prostatectomy is that
two out of eight patients had residual cancer on protocol
biopsy. Although these patients have not required
any further treatment as of the writing of this paper, it
suggests that there is room for improvement in selection
of the patients. For the reasons explained above, we are
not convinced that mp-MRI would eliminate the rate
of residual cancer, as this study and others suggest that
a substantial proportion of clinically significant tumors
are below the detection limits of mp-MRI.18 32 33 36 We are
exploring an alternate diagnostic methodology to accu-
rately stage focal therapy candidates preoperatively with
3D transperineal saturation biopsy.37 Biopsies that target
specifically the area of the prostate that will be left behind
during precision prostatectomy may complement biop-
sies that target the tissue that is removed, and thus reduce
the incidence of missed cancer.
It can also be argued that cancer control requires the
treatment of just the index lesion. This conclusion is
controversial. Kneppers et al showed that in about 20%
of men, lymph node metastases arose from non-index
lesions.38 In a more recent study, the Palapattu group
demonstrated that, using next generation sequencing,
the genetic footprint of MRI invisible lesions was indis-
tinguishable from MRI visible or index lesions.39 Further,
the short duration of follow-up and the high incidence of
secondary treatment after focal HIFU argue for the devel-
opment of newer approaches, a better mouse trap, if you
will. It seems reasonable to plead that if new procedures
are being contemplated, their development should follow
a structured pattern, the IDEAL path.
Finally, conclusions about functional superiority are
best resolved with randomized clinical trials. We are in
the process of doing such a trial. The data reported here
merely form a basis of such a trial.
CONCLUSIONS
Whole-gland therapy of CaP provides excellent cancer
control, but results in a high rate of erectile dysfunction.
Focal ablative therapy eliminates sexual dysfunction,
but at the cost of leaving residual cancer. We propose a
novel surgical approach to localized CaP similar to the
surgical treatment of breast cancer. Precision prosta-
tectomy is feasible, safe, offers excellent postoperative
functional recovery, and promises superior oncological
control (compared to ablative technologies). For now,
precision prostatectomy may defer or avoid the need
for immediate whole-gland therapy in 80% of men with
intermediate-risk CaP, while reducing the risk of postop-
erative erectile dysfunction. However, longer follow-up
with randomized trials is necessary to properly define the
exact role of precision prostatectomy in the treatment of
men with localized CaP.
Contributors Study design and conception: MM. Administrative support: MM. Data
collection, analysis and interpretation: AS, WJ, KT, FA, IPZ, SA, NG, MM. Drafting of
the manuscript: AS, MM. Revision of the manuscript: AS, MM.
Funding The authors have not declared a specic grant for this research from any
funding agency in the public, commercial or not-for-prot sectors.
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Commissioned; externally peer reviewed.
Data availability statement Data are available on request.
Open access This is an open access article distributed in accordance with the
Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which
permits others to distribute, remix, adapt, build upon this work non-commercially,
and license their derivative works on different terms, provided the original work is
properly cited, appropriate credit is given, any changes made indicated, and the use
is non-commercial. See:http:// creativecommons. org/ licenses/ by- nc/ 4. 0/.
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... In an effort to improve on the oncologic drawbacks of existing ablative FT techniques and active surveillance (undertreatment) and the functional shortcomings of radical therapies (overtreatment), we developed a novel surgical technique for subtotal resection of the prostate, called precision prostatectomy [41][42][43]. This technique allows maximal prostatic tissue extirpation (>90% tissue is removed) without affecting the functional reserve [41][42][43][44]. ...
... In an effort to improve on the oncologic drawbacks of existing ablative FT techniques and active surveillance (undertreatment) and the functional shortcomings of radical therapies (overtreatment), we developed a novel surgical technique for subtotal resection of the prostate, called precision prostatectomy [41][42][43]. This technique allows maximal prostatic tissue extirpation (>90% tissue is removed) without affecting the functional reserve [41][42][43][44]. Here we provide a technical description of this novel surgical procedure and report on functional and oncologic outcomes in a cohort of 88 men who underwent this procedure as part of an IDEAL (Idea, Development, Exploration, Assessment and Long-term Follow-up) stage 1-2b prospective development study. ...
... The current investigation was a single-arm, single-center IDEAL stage 1-2b prospective development study [45][46][47] and followed our IDEAL stage 0 (preclinical) and 1 (early clinical) studies that laid the theoretical foundation for precision prostatectomy and established its feasibility, respectively [41,42] [48], telephone interviews, and in-person visits. ...
Article
Background The existing treatment options for men with intermediate- or high-volume low-risk prostate cancer (PCa) are associated with a substantial risk of over- or undertreatment. The development of risk-adjusted therapies is an unmet need for these patients. Objective To describe our novel technique of precision prostatectomy, a form of surgical focal therapy that allows radical excision of the index PCa lesion along with >90% prostatic tissue extirpation while preserving the prostatic capsule and seminal vesicle/vas deferens complex on the side contralateral to the dominant cancer lesion, and to report on medium-term functional and oncologic outcomes in the first 88 consecutive men who underwent this procedure between December 2016 and January 2020. Design, setting, and participants Men with (1) prostate-specific antigen (PSA) ≤20 ng/ml, (2) clinical T stage ≤cT2, (3) a dominant unilateral lesion with Gleason ≤ 4 + 3 disease with any number or percentage of cores involved ipsilaterally on prostate biopsy, (4) no primary Gleason ≥4 lesion contralaterally, and (5) a preoperative Sexual Health Inventory of Men (SHIM) score of ≥17 (out of 25) with/without phosphodiesterase type-5 inhibitor use who consented to undergo precision prostatectomy were included in this single-arm, single-center, IDEAL stage 2b prospective development study. Intervention Robotic precision prostatectomy. Outcome measurements and statistical analysis The safety and urinary, sexual, and oncologic outcomes of the precision prostatectomy technique were studied. Descriptive statistics and Kaplan-Meier analyses were used to assess 12-mo urinary continence (0–1 pad), 12-mo sexual potency (SHIM score ≥17), 36-mo freedom from clinically significant PCa (grade group ≥2), secondary treatments, metastatic disease, and mortality. Results and limitations At study entry, the median age, PSA, and SHIM score were 60.0 yr (interquartile range [IQR] 54.2–65.9), 5.7 ng/ml (IQR 4.2–7.1), and 22 points (IQR 19–24), respectively. The median follow-up was 25 mo (IQR 14–38). At 12 mo, all patients were continent (0–1 pads), with 90.9% of patients using 0 pads. The median time to urinary continence was 1 mo (IQR 1–4). At 12 mo, 85% of all-comers and 90.2% of the preoperatively potent men were potent. The median time to sexual potency was 4 mo (IQR 4–12). From an oncologic standpoint, at 36 mo an estimated 93.4% of the patients were free from clinically significant residual PCa and 91.7% had not undergone any additional treatment. All patients were alive and free of metastatic disease at 36 mo. Conclusions Precision prostatectomy is technically safe and reproducible and offers excellent postoperative functional results. At 36-mo follow-up, the oncologic outcomes and secondary treatment rates appear to be superior to existing ablative focal therapy results. Pending long-term data, a risk-stratified surgical approach to PCa may avoid whole-gland therapy and preserve functional quality of life in men with localized PCa. Patient summary Precision prostatectomy is a new form of focal therapy for intermediate-risk prostate cancer in which a 5–10-mm rim of prostate capsule is left on the opposite side of the gland to where the dominant cancer is located. The technique appears to be safe and efficacious and adds to the growing armamentarium of risk-adapted therapies for treatment of localized prostate cancer that avoid the adverse effects on urinary and erectile function of whole-gland treatments.
... The robotic precision prostatectomy spares a 5-10 mm rim of prostate tissue unilaterally saving the ipsilateral neurovascular bundle in toto, while removing >90% of the gland along with the dominant cancer lesion. We recently reported on the short-term results in the first 8 patients that we had treated using this focal surgical approach (10,11). In this article, we sought to accomplish two goals: First, to provide an update on the safety, and functional and oncological outcomes in the first 25 consecutive men that have undergone precision prostatectomy and have greater than 2 years of followup, and second, to identify men within the Surveillance Epidemiology and End Results (SEER) data-registry that have undergone non-radical/focal treatment (surgical or ablative) for CaP over the years of registry subsistence, and assess long-term cancer survival outcomes in them. ...
... Men meeting the criteria: (I) PSA ≤15 ng/mL, (II) stage ≤cT2, (III) dominant unilateral lesion with Gleason score ≤4+3 with any number of cores or percentage (%) cores involved ipsilaterally on TRUS prostate biopsy, (IV) no primary Gleason score ≥4 contralaterally on TRUS prostate biopsy, and (V) preoperatively potent with/without PDE-5 inhibitors were included in this IDEAL stage 2b prospective study (10,11). ...
... The difference was in the way the nerve-sparing was performed: A conventional nerve-sparing was performed on the side of the dominant cancer lesion, while, on the contralateral side (the precision side), the dissection was started anterior to the vas deferens/seminal vesicle complex, preserving all layers of Denonvilliers' fascia, with the included erectogenic nerves (14,15). The dissection was then continued 5-10 mm into the prostatic capsule, deliberately attempting to leave behind a thin rim of prostatic capsule/peripheral tissue (5-10 mm) along with the seminal vesicle/ejaculatory duct complex (10,11). Systematic needle biopsies (via a suprapubic or transperineal approach) were taken from the remnant prostatic tissue, and sent for frozen section analysis. ...
Article
Background: We recently described a novel form of focal therapy for prostate cancer (CaP)-the precision prostatectomy. Here we report on the first 25 consecutive patients. Further, utilizing Surveillance Epidemiology and End Results (SEER)-registry data, we assess long-term oncological efficacies of various focal therapy techniques. Methods: Men who met the criteria: (I) PSA ≤15 ng/mL, (II) stage ≤cT2, (III) dominant unilateral lesion with Gleason ≤4+3 with any number or percentage (%) of cores involved ipsilaterally on biopsy, (IV) no primary Gleason ≥4 contralaterally, and (V) preoperative erectile function score (IIEF-5/SHIM) of ≥17 with/without PDE-5i were included in this prospective, single-arm, IDEAL stage 2b study (December 2016 to July 2017). Safety of the technique, and intermediate-term urinary, sexual and oncological outcomes were studied. Descriptive statistics and Kaplan-Meier (KM) analysis were used to assess 12-month urinary continence (0-1 pad), 12-month sexual potency (SHIM ≥17), and 36-month freedom from clinically-significant CaP (grade group ≥2), radical treatment, metastatic disease and mortality. SEER-registry was queried to evaluate CaP-specific survival in patients undergoing hyperthermia, cryotherapy, or segmental prostatectomy. Results: At study entry, the median (IQR) age, PSA and SHIM score were 56.5 (53.1-62.3) years, 4.2 (3.8-5.9) ng/mL and 23 [20-25], respectively. Only 1 patient met the Epstein criteria for active surveillance. All patients were followed for a minimum of 2 years. At 12 months, from a functional standpoint, all patients were continent. Twenty-three (92%) patients were potent at 12 months. From an oncological standpoint, at 36 months, the KM analysis (95% CI) demonstrated a 96.2% (92.9-98.7) rate of freedom from clinically-significant CaP and a 92.7% (88.9-97.2) rate of freedom from radical treatment. All patients were alive and free of metastatic disease at the latest follow-up. Analysis of the SEER-registry data demonstrated 10-year CaP-specific survival rates of 91.6% to 97.7% among the 3 studied modalities, P=0.298. Conclusions: Precision prostatectomy is feasible, technically safe, and offers excellent postoperative functional results. At 36 months of follow-up, the oncological outcomes and secondary procedure rates appear to be at-par with the ablative forms of focal therapy.
... We hypothesized that the high anatomical failure rate after focal HIFU may be related to two concurrent issues: the presence of clinically significant CaP lesions below the detection resolution of existing MRI technology, currently 10 mm in diameter or 0.5 cm 3 in volume [12], and the existence of field cancerization in prostatic tissue [13]. A preclinical, IDEAL stage 0, prostatic mapping study we carried out verified this assumption [14]. We found that >70% of subjects who were candidates for focal or hemiablation therapy harbored low-volume clinically significant CaP on analysis of whole-mount radical prostatectomy specimens. ...
... If cancer is present on frozen intraoperative sections, the operation is converted to radical prostatectomy. More details can be found elsewhere [14]. ...
... We are in the process of conducting a blinded, doublearm randomized trial and the data are embargoed. However, we can share preliminary results that have been published [14]: in our study of eight patients, the precision prostatectomy seemed to offer several potential benefits over focal/hemiablation. No patients needed to be excluded because of prostate size or the location of the tumor. ...
Article
Precision prostatectomy may allow patients to choose a risk-stratified surgical approach for treatment of localized prostate cancer.
... [12][13][14] To address the issues outlined previously, we have developed a novel surgical technique-known as the precision prostatectomy procedure-that aims to remove ~95% of the prostate while maximally preserving the erectogenic nerves that run alongside the prostate capsule. [15][16][17] During this procedure, men undergo a standard radical prostatectomy on one side along with a contralateral subtotal prostatectomy, leaving the patient with several millimetre rims of tissue that contains the erectogenic nerves. We have previously reported the highly favorable results of 88 patients who underwent this novel procedure. ...
Article
Objective: To assess the impact of iterative changes in preoperative and postoperative biopsy techniques on the outcomes of men undergoing the precision prostatectomy procedure. Precision prostatectomy is a novel surgical treatment for prostate cancer that aims to maximally preserve erectogenic nerves via partial preservation of the prostate capsule. Design: Retrospective. Setting: Single tertiary care center. Participants: This study included 120 patients who consented to undergo prostate cancer treatment with the precision prostatectomy procedure. Patients were originally enrolled in one of two separate prospective protocols studying precision prostatectomy. Interventions: Preoperatively, 60 patients were screened with transrectal (TR) biopsy and 60 were screened by transperineal (TP) biopsy. Ultimately, 117 patients underwent precision prostatectomy. Of the 43 postoperative biopsies, 19 were TR; 17 were TP with ultrasound; and 7 were TP with microultrasound (mUS). Main outcome measures: Preoperatively, we evaluated whether the transition to TP biopsy was associated with differences in postoperative treatment failure defined as a neoplasm-positive postoperative biopsy. Postoperative biopsies were compared with respect to their ability to sample the remnant tissue, specifically percentage of cores positive for prostate tissue. Results: Preoperatively, 9/60 (15%) positive postoperative biopsies occurred in the TR group and 6/60 (10%) in the TP group; Kaplan-Meier survival estimates did not differ between groups (p=0.69 by log rank). Postoperatively, the numbers of cores positive for prostate tissue were 99/160 (62%), 63/107 (59%), and 36/39 (92%) in the TR biopsy, TP with ultrasound, and TP with mUS groups, respectively; this difference was statistically significant versus the rate in the TR and standard TP groups (p=0.0003 and 0.0002). Conclusion: We found no significant improvement in patient screening, preoperatively-though limited by small sample size and relatively short follow-up. The incorporation of high-frequency mUS for postoperative biopsies improved the ability to sample the remnant tissue with a higher efficiency.
Article
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Background: To identify the periprostatic structures associated with early return of urinary continence after radical prostatectomy (RP). Methods: We compared total continence results between four different techniques of robot-assisted radical prostatectomy (RARP). Specifically, we studied 1-week and 1-month zero-pad continence rates of anterior (n = 60), posterior (n = 59), a novel hybrid posterior-anterior (n = 12), and transvesical (n = 12) approaches of RARP. Each technique preserved a unique set of periprostatic anatomic structures, thereby, allowing evaluation of the individual impact of preservation of nerves, bladder neck, and space of Retzius with associated anterior support structures on early continence. Urethral length was preserved in all approaches. The space of Retzius was preserved in posterior and transvesical approaches, while the bladder neck was preserved in posterior and hybrid approaches. Nerve sparing was done per preoperative oncological risk. For all patients, 24-h pad usage rates and 24-h pad weights were noted at 1 week and 1 month after catheter removal. Multivariable logistic regression analysis was performed to identify predictors of early continence. Data were obtained from prospective studies conducted between 2015 and 2021. Results: At 1 week, 15%, 42%, 45%, and 8% of patients undergoing anterior, posterior, hybrid, and transvesical RARP approaches, respectively, were totally continent (p = 0.003). These rates at 1 month were 35%, 66%, 64%, and 25% (p = 0.002), respectively. The transvesical approach, which preserved the space of Retzius but not the bladder neck, was associated with the poorest continence rates, while the posterior and hybrid approaches in which the bladder neck was preserved with or without space of Retzius preservation were associated with quickest urinary continence recovery. Bladder neck preservation was the only significant predictor of 1-week and 1-month total continence recovery in adjusted analysis, Odds ratios 9.06 (p = 0.001) and 5.18 (p = 0.004), respectively. Conclusions: The beneficial effect of the Retzius-sparing approach on early continence recovery maybe associated with bladder neck preservation rather than space of Retzius preservation.
Article
Results after radical prostatectomy (RP) are generally judged by complete removal of the cancer, return of urinary control, and the ability to have intercourse. Given the complexity of the anatomy of the prostate and its relationship to the surrounding nerves, muscles, and fascia, RP is considered a challenging and technically demanding surgery. Here we propose multiple intraoperative strategies to optimize oncological and functional outcomes.
Article
Purpose of review: Urinary incontinence and erectile dysfunction are common after radical prostatectomy. These side effects greatly impact patients' quality of life. Therefore, surgical techniques and technology tools are constantly being developed to optimize trifecta outcomes. Here we focus on advances in nerve-sparing (NS) and continence preservation. Recent findings: New surgical techniques dedicated to preservation rather than reconstruction have been developed to improve urinary continence (UC) and NS. On the other hand, intraoperative assessment of prostatic and periprostatic structures has shown promising outcomes toward NS whereas avoiding omission of extracapsular extension (ECE). Likewise, neural regeneration strategies are under research to improve return of erectile function and UC. Summary: Superb outcomes after Robot-Assisted Radical Prostatectomy require a proper balance between NS and risk of ECE. Detailed anatomic knowledge together with an accurate surgical planning are cornerstone for tailoring the approach in each case.
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Purpose: Multiparametric magnetic resonance imaging (mpMRI) is used widely for prostate cancer (PCa) evaluation. Approximately 35% of aggressive tumors, however, are not visible on mpMRI. We sought to identify the molecular alterations associated with mpMRI-invisible tumors and determine whether mpMRI visibility is associated with PCa prognosis. Methods: Discovery and validation cohorts included patients who underwent mpMRI before radical prostatectomy and were found to harbor both mpMRI-visible (Prostate Imaging and Reporting Data System 3 to 5) and -invisible (Prostate Imaging and Reporting Data System 1 or 2) foci on surgical pathology. Next-generation sequencing was performed to determine differential gene expression between mpMRI-visible and -invisible foci. A genetic signature for tumor mpMRI visibility was derived in the discovery cohort and assessed in an independent validation cohort. Its association with long-term oncologic outcomes was evaluated in a separate testing cohort. Results: The discovery cohort included 10 patients with 26 distinct PCa foci on surgical pathology, of which 12 (46%) were visible and 14 (54%) were invisible on preoperative mpMRI. Next-generation sequencing detected prioritized genetic mutations in 14 (54%) tumor foci (n = 8 mpMRI visible, n = 6 mpMRI invisible). A nine-gene signature (composed largely of cell organization/structure genes) associated with mpMRI visibility was derived (area under the curve = 0.89), and the signature predicted MRI visibility with 75% sensitivity and 100% specificity (area under the curve = 0.88) in the validation cohort. In the testing cohort (n = 375, median follow-up 8 years) there was no significant difference in biochemical recurrence, distant metastasis, or cancer-specific mortality in patients with predicted mpMRI-visible versus -invisible tumors (all P > .05). Conclusion: Compared with mpMRI-invisible disease, mpMRI-visible tumors are associated with underexpression of cellular organization genes. mpMRI visibility does not seem to be predictive of long-term cancer outcomes, highlighting the need for biopsy strategies that detect mpMRI-invisible tumors.
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Purpose: We assessed the outcomes of high-intensity focused ultrasound for the primary treatment of localized prostate cancer in a retrospective series. This represents one of the largest published series of intermediate and high-risk patients. Materials and methods: A retrospective, multicenter analysis of patients who underwent partial gland ablation (PGA) between January 2013 to September 2017 was performed. Patients with biopsy-proven localized disease and limited multifocality based on MRI, who preferred a minimally invasive outpatient treatment, were treated with the Sonablate 500 system. Oncological and functional outcomes, as well as risk factors for recurrence, were analyzed. Results: A total of 166 procedures were performed in 150 patients. Grade group ≥ 2 was present in 89% cases. Mean follow-up was 24.3 ± 14.4 months. Mean prostatic-specific antigen decreased 65% from 7.9 ± 6.8 ng/ml to a nadir of 2.7 ± 3.1 ng/ml. Confirmatory biopsies were performed in 87 (52%) high-risk for recurrence patients. Clinically significant cancer (Grade Group ≥ 2) was detected in 37 (42%) cases. Patients with a higher number of positive cores, medial tumor location, or with higher prostatic specific antigen values had higher probabilities of recurrence. Thirty-seven (24.6%) patients underwent salvage treatment, including 16 repeatedPGAs. Conclusions: PGA with high-intensity focused ultrasound therapy is safe and has a minimal impact on functional outcomes. Local recurrence/failure occurred in 42% of the patients who were at high risk for recurrence. Medially located tumors had a higher failure rate. Serious complications were rare. Whole gland treatment was avoided in 81% of patients.
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Background: Clinically significant nonmetastatic prostate cancer (PCa) is currently treated using whole-gland therapy. This approach is effective but can have urinary, sexual, and rectal side effects. Objective: To report on 5-yr PCa control following focal high-intensity focused ultrasound (HIFU) therapy to treat individual areas of cancer within the prostate. Design, setting, and participants: This was a prospective study of 625 consecutive patients with nonmetastatic clinically significant PCa undergoing focal HIFU therapy (Sonablate) in secondary care centres between January 1, 2006 and December 31, 2015. A minimum of 6-mo follow-up was available for599 patients. Intermediate- or high-risk PCa was found in 505 patients (84%). Intervention: Disease was localised using multiparametric magnetic resonance imaging (mpMRI) combined with targeted and systematic biopsies, or transperineal mapping biopsies. Areas of significant disease were treated. Follow-up included prostate-specific antigen (PSA) measurement, mpMRI, and biopsies. Outcome measurements and statistical analysis: The primary endpoint, failure-free survival (FFS), was defined as freedom from radical or systemic therapy, metastases, and cancer-specific mortality. Results and limitations: The median follow-up was 56 mo (interquartile range [IQR] 35-70). The median age was 65 yr (IQR 61-71) and median preoperative PSA was 7.2 ng/ml (IQR 5.2-10.0). FFS was 99% (95% confidence interval [CI] 98-100%) at 1 yr, 92% (95% CI 90-95%) at 3 yr, and 88% (95% 85-91%) at 5 yr. For the whole patient cohort, metastasis-free, cancer-specific, and overall survival at 5 yr was 98% (95% CI 97-99%), 100%, and 99% (95% CI 97-100%), respectively. Among patients who returned validated questionnaires, 241/247 (98%) achieved complete pad-free urinary continence and none required more than 1 pad/d. Limitations include the lack of long-term follow-up. Conclusions: Focal therapy for select patients with clinically significant nonmetastatic prostate cancer is effective in the medium term and has a low probability of side effects. Patient summary: In this multicentre study of 625 patients undergoing focal therapy using high-intensity focused ultrasound (HIFU), failure-free survival, metastasis-free survival, cancer-specific survival, and overall survival were 88%, 98%, 100%, and 99%, respectively. Urinary incontinence (any pad use) was 2%. Focal HIFU therapy for patients with clinically significant prostate cancer that has not spread has a low probability of side effects and is effective at 5 yr.
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Patient summary: Focal therapy of prostate cancer is the targeted destruction of cancer within a specific part of the prostate gland, sparing the rest of the prostate and nearby tissue. This procedure could potentially reduce side effects when compared with established standard treatments, such as surgery or radiotherapy, which treat the entire prostate. Studies show that for most men with low-risk cancer, active surveillance is the preferred treatment option. However, the available data regarding all forms of focal therapy are still poor and inconclusive. Consequently, due to both the lack of clear results associated with focal therapy and the difficulties in detecting all cancerous areas of the prostate, focal therapy should be considered an investigational modality only.
Article
Sampling error is an inherent problem of prostate biopsy. Consequently, there are problems in determining whether a given carcinoma is clinically significant on the basis of biopsy results. This study assesses the factors that predispose to errors in biopsy grading, as well as the dimensions of sampling error due to these factors. Among 187 cases, biopsy grading error was retrospectively related to grade heterogeneity in the prostate and to biopsy‐related factors. Clinically relevant biopsy grading errors occurred in a quarter of the cases. Of all grading errors, at least 17% resulted from misinterpretation by the pathologist only. Overall, prostates with grade heterogeneity revealed grading errors twice as frequently as specimens without grade heterogeneity. In most cases, however, grading error resulted from multiple factors, such as the number and length of cores obtained (p<0.05). This was an important finding because the mean core length was only 9.4 mm, whereas the biopsy needle is designed to obtain cores of 15 mm. Moreover, clinically relevant biopsy grading error had occurred in almost half of the cases when the Gleason score was based on a tumour deposit measvring less than 0.5 mm (p<0.05). The clinical consequences of these findings are important. Clinicians should try to obtain at least six biopsies, each 15 mm in length, to minimize grading error. Pathologists should be cautious in reporting Gleason scores based on tumour lesions smaller than 400x total magnification field. Interpretation could be refined, when necessary, by warning the urologist of the Limitations of the biopsy report. Copyright © 2000 John Wiley & Sons, Ltd.
Article
Importance Magnetic resonance imaging (MRI) guidance improves the accuracy of prostate biopsy for the detection of clinically significant prostate cancer, but the optimal use of such guidance is not yet clear. Objective To determine the cancer detection rate (CDR) of targeting MRI-visible lesions vs systematic prostate sampling in the diagnosis of clinically significant prostate cancer in men who were biopsy naive. Design, Setting, and Participants This paired cohort trial, known as the Prospective Assessment of Image Registration in the Diagnosis of Prostate Cancer (PAIREDCAP) study, was conducted in an academic medical center from January 2015 to April 2018. Men undergoing first-time prostate biopsy were enrolled. Paired-cohort participants were a consecutive series of men with MRI-visible lesions (defined by a Prostate Imaging Reporting & Data System version 2 score ≥ 3), who each underwent 3 biopsy methods at the same sitting: first, a systematic biopsy; second, an MRI-lesion biopsy targeted by cognitive fusion; and third, an MRI-lesion targeted by software fusion. Another consecutive series of men without MRI-visible lesions underwent systematic biopsies to help determine the false-negative rate of MRI during the trial period. Main Outcomes and Measures The primary end point was the detection rate of clinically significant prostate cancer (Gleason grade group ≥2) overall and by each biopsy method separately. The secondary end points were the effects of the Prostate Imaging Reporting & Data System version 2 grade, prostate-specific antigen density, and prostate volume on the primary end point. Tertiary end points were the false-negative rate of MRI and concordance of biopsy-method results by location of detected cancers within the prostate. Results A total of 300 men participated; 248 had MRI-visible lesions (mean [SD] age, 65.5 [7.7] years; 197 were white [79.4%]), and 52 were control participants (mean [SD] age, 63.6 [5.9] years; 39 were white [75%]). The overall CDR was 70% in the paired cohort group, achieved by combining systematic and targeted biopsy results. The CDR by systematic sampling was 15% in the group without MRI-visible lesions. In the paired-cohort group, CDRs varied from 47% (116 of 248 men) when using cognitive fusion biopsy alone, to approximately 60% when using systematic biopsy (149 of 248 men) or either fusion method alone (154 of 248 men), to 70% (174 of 248 men) when combining systematic and targeted biopsy. Discordance of tumor locations suggests that the different biopsy methods detect different tumors. Thus, combining targeting and systematic sampling provide greatest sensitivity for detection of clinically significant prostate cancer. For all biopsy methods, the Prostate Imaging Reporting & Data System version 2 grade and prostate-specific antigen density were directly associated with CDRs, and prostate volume was inversely associated. Conclusions and Relevance An MRI-visible lesion in men undergoing first-time prostate biopsy identifies those with a heightened risk of clinically significant prostate cancer. Combining targeted and systematic biopsy offers the best chances of detecting the cancer.
Article
Primary prostate cancer lesions are clonally heterogeneous and often arise independently. In contrast, metastases were reported to share a monoclonal background. Because prostate cancer mortality is the consequence of distant metastases, prevention of metastatic outgrowth by primary tumor ablation is the main focus of treatment for localized disease. Focal therapy is targeted ablation of the primary index lesion, but it is unclear whether remaining primary lesions metastasize at a later stage. In this study, we compared copy number aberration profiles of primary prostate cancer lesions with matching pelvic lymph node metastases of 30 patients to establish clonality between a lymph node metastasis and multiple primary lesions within the same patient. Interestingly, in 23.3% of the cases, the regional metastasis was not clonally linked to the index primary lesion. These findings suggest that focal ablation of only the index lesion is potentially an undertreatment of a significant proportion of prostate cancer patients.
Article
Background Radical prostatectomy reduces mortality among men with clinically detected localized prostate cancer, but evidence from randomized trials with long-term follow-up is sparse. Methods We randomly assigned 695 men with localized prostate cancer to watchful waiting or radical prostatectomy from October 1989 through February 1999 and collected follow-up data through 2017. Cumulative incidence and relative risks with 95% confidence intervals for death from any cause, death from prostate cancer, and metastasis were estimated in intention-to-treat and per-protocol analyses, and numbers of years of life gained were estimated. We evaluated the prognostic value of histopathological measures with a Cox proportional-hazards model. Results By December 31, 2017, a total of 261 of the 347 men in the radical-prostatectomy group and 292 of the 348 men in the watchful-waiting group had died; 71 deaths in the radical-prostatectomy group and 110 in the watchful-waiting group were due to prostate cancer (relative risk, 0.55; 95% confidence interval [CI], 0.41 to 0.74; P<0.001; absolute difference in risk, 11.7 percentage points; 95% CI, 5.2 to 18.2). The number needed to treat to avert one death from any cause was 8.4. At 23 years, a mean of 2.9 extra years of life were gained with radical prostatectomy. Among the men who underwent radical prostatectomy, extracapsular extension was associated with a risk of death from prostate cancer that was 5 times as high as that among men without extracapsular extension, and a Gleason score higher than 7 was associated with a risk that was 10 times as high as that with a score of 6 or lower (scores range from 2 to 10, with higher scores indicating more aggressive cancer). Conclusions Men with clinically detected, localized prostate cancer and a long life expectancy benefited from radical prostatectomy, with a mean of 2.9 years of life gained. A high Gleason score and the presence of extracapsular extension in the radical prostatectomy specimens were highly predictive of death from prostate cancer. (Funded by the Swedish Cancer Society and others.)
Article
Background: The last decade has seen several advances in radical prostatectomy (RP) technique and post-RP care that are relevant to erectile function (EF) recovery. Objective: We examined whether these practice changes have led to observed improvements in EF rates over time. Design, setting, and participants: We identified 2364 patients treated with either open or minimally-invasive RP at a single academic center in 2008-2015. To mitigate confounding by the surgical learning curve, only patients treated by surgeons who performed at least 100 procedures were considered. Intervention: EF before and after RP was assessed by the International Index of Erectile Function 6 (IIEF-6), with recovery defined as IIEF-6 ≥24. Outcome measurements and statistical analysis: We analyzed EF recovery rates of patients treated with bilateral nerve-sparing surgery and free from adjuvant/salvage treatment at the time of EF assessment. Local polynomial regression analyses explored changes in the outcomes over time. Linear and logistic regression analyses were used to estimate the influence of year of surgery on baseline variables and EF recovery. Results and limitations: We observed a significant decrease over time of the EF recovery rates at both 12 and 24mo post-RP (all p=0.01). However, patient's age at surgery increased over time (mean increase of 0.5 per year; p<0.01), with a resultant increase in risk of comorbidity (odds ratio [OR]=1.1, 95% confidence interval [CI]: 1.02-1.15; p=0.008) and thus decrease in baseline IIEF-6 score (0.35 points per year; p=0.0003). After accounting for baseline and pathological characteristics, urinary function, and type of surgery in a multivariable analysis, year of surgery was not associated with EF recovery (12mo: OR=0.97, 95% CI: 0.91-1.03, p=0.4; 24mo: OR=0.97, 95% CI: 0.91-1.03, p=0.3). Conclusions: Findings from a high-volume center suggest that, despite the advancements in surgical and postoperative care, EF outcomes after RP have not improved over the last decade. Additional strategies are required to improve EF recovery after RP. Patient summary: The probability of regaining potency after surgery for prostate cancer did not improve over the last decade; more efforts are needed to improve patient's care after radical prostatectomy.