Transcript Locally Advanced and Metastatic Prostate Cancer

Cytoreductive Prostatectomy
Mark L. Gonzalgo, M.D., Ph.D.
Professor & Chief of Urology
University of Miami Hospital
Associate Director for Clinical Affairs
Sylvester Comprehensive Cancer Center
University of Miami Miller School of Medicine
Locally Advanced
and Metastatic Prostate Cancer
 5-15% of newly diagnosed prostate cancers
are locally advanced or metastatic
 Survival rates for metastatic prostate cancer
remain poor
 Standard of care for metastatic prostate
cancer is systemic treatment, but is there a
role for local therapy?
Role of Local Treatment of Primary
Tumor
 Survival benefit shown for other
malignancies:
 Renal Cell
 Colorectal
 Intracranial Glioma
 Ovarian
 Breast
Proposed Rationale for Cytoreductive
Prostatectomy
 Reasonable mechanistic theories with some basic science data
exist:
 Tumor debulking
Removing tumor-promoting factors and immunosuppressive
cytokines increased response to ADT after RP
 “Seed and soil” hypothesis
Receptive microenvironment may be driven by factors secreted
by the primary tumor. Development of individual metastases is
dependent on an intact primary tumor focus
 Tumor self-seeding
Circulating tumor cells return to and grow in primary tumor
sites from derived metastases
What is Oligometastatic?
 No consensus definition
 ≤ 3 lesions outside of the treated primary tumor
 Randomized phase II trials
SABR-COMET in Canada = 5 oligometastasis
 STOMP in Belgium = 3 oligometastasis
 CORE in the UK (includes prostate, breast, and
lung cancer with 3 oligometastasis)
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Locally Advanced
and Metastatic Prostate Cancer
 No clinical trial has assessed the role of RT in
patients with node-positive N+M0 disease
 STAMPEDE Trial – Control Arm
 Exploratory
multivariate analysis of the impact
of RT on survival and failure-free survival
 Control arm of the STAMPEDE Trial
 721 men with newly diagnosed M0 disease were
included:
 Radiotherapy encouraged but not mandated for
N0M0 patients only (since November 2011)
 Failure-free survival outcomes favored use of RT for
patients with both N0M0 (HR, 0.33 [95% CI, 0.18-0.61])
and N+M0 disease (HR, 0.48 [95% CI, 0.29-0.79]).
 Data suggest that benefits of RT extend to men with
N+M0 disease
James et al., JAMA Oncol, 2016
James et al., JAMA Oncol, 2016
 3,540 patients with cN+ prostate cancer without
distant metastases between 2004 and 2011
 32.2% men treated with ADT alone
 51.4% received ADT+RT
 Propensity score matching: 318 patients in each
group
 Statistically significant overall survival benefit for
patients with cN+ prostate cancer treated with
ADT+RT compared to ADT alone
Lin et al., JNCI 2015
Lin et al., JNCI 2015
 Retrospective study 0f
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SEER data
2004 – 2010
8,185 patients
Stage IV (M1a-c) PC
Radical prostatectomy
(RP) vs.
Brachytherapy (BT) vs.
No surgery or radiation
therapy (NSR)
38% of men died from prostate cancer with median follow-up of 16 months
5-yr OS
 RP
67.4%
 BT
52.6%
 NSR 22.5%
RP and BT were independently associated with better overall survival
compared to no surgery or radiation
Cumulative incidence of cancer-specific mortality
RP and BT were associated with decreased cancer-specific mortality
compared to no surgery or radiation
Subgroup Analysis
 Factors independently associated
with increased mortality in
localized therapy:
 age ≥ 70 yr
 cT4
 high grade disease
 PSA ≥ 20 ng/ml
 pelvic lymphadenopathy
 5 year OS:
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≤ 1 factor - 77.3%
2 factors- 53.1%
≥ 3 factors - 38.2% - similar to
NSR
Culp et al., Eur Urol, 2014
Limitations
 Selection bias
 No
 No
data on comorbidities
data about adjuvant ADT or
chemotherapy
 No data on extent of bony metastasis
 Patients treated with RP were 10 years
younger than the NSR group (62 vs 72)
 RP patients had a higher proportion of
those with PSA < 20
 No discussion on the impact on quality of
life or complications of treatment
 Examined perioperative outcomes and short-
term complications after radical prostatectomy
for locally resectable, distant metastatic prostate
cancer
 Retrospective case series from 2007 to 2014:
 106 patients with newly diagnosed metastatic
(M1) prostate cancer from USA, Germany,
Italy, and Sweden
 Outcome measures: margin status,
continence, readmission, reoperation, and
overall complication rates at 90 days
 79.2% of patients had no complications
 Positive-margin rate = 53.8%
 94/106 (88.7%) men were alive at a
median follow-up of 22.8 months
Multi-institutional Analysis of Perioperative Outcomes in 106 Men
Who Underwent Radical Prostatectomy for Distant Metastatic
Prostate Cancer at Presentation (Sooriakumaran, et al.)
Retrospective. Comparison to meta-analysis
of prostatectomy for standard indications.
(Tewari, et al.)
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Overall complications ~ 20.8% (8.2 -19.4)
Readmission ~ 3.8% (3.0)
Reoperation ~ 1.9% (2.3)
Transfusion rates ~ 14.2% (16.5)
Mean length of stay ~ 3.1 days (3.0)
Wound infections ~ 4.7% (2.8)
Positive margin rate ~ 54% (42.6)
Take home message: Radical prostatectomy is technically feasible
and safe in men with metastatic prostate cancer
Developed a predictive model for 3 year cancer
specific mortality risk based on:
 Age at diagnosis
 PSA level
 Gleason score
 T stage
 N stage
 M stage
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LT compared with NLT conferred higher CSM-free
survival rate in patients with a predicted CSM risk < 40%
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LT did not provide a survival benefit when the
predicted CSM risk > 50%
 11 patients with oligometastatic disease treated
with RP and extendend PLND
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Oligometastatic: ≤ 5 bone lesions at bone scan with or
without suspicious nodal involvement
 10 patients had LN invasion
 8 patients had positive SM
 ADT was administered to 10 patients
CSM-free survival = 82%
7 year clinical progression-free survival = 45%
Conclusions
 Data for support of cytoreductive prostatectomy
remains limited
 Clinical Trials are necessary:
 Some evidence exists for safety in
perioperative period and technically feasibility
 Little evidence for long term safety/morbidity
 Reasonable mechanistic theories
 Prospective cohort studies for other cancers lend
credibility
Future Directions
 TRoMbone: 5 year OS of radical prostatectomy plus usual
treatment vs. usual treatment alone in oligometastatic PC
 STAMPEDE (NCT00268476): ADT vs multiple arms
including ADT+RP
 NCT01751438: Systemic + local (radiation or surgery) vs
systemic alone in M1 mPC
 NCT00924469 and NCT01547299: Neoadjuvant androgen
deprivation therapy to RP