TY - JOUR
T1 - Comparison between adjuvant and early-salvage postprostatectomy radiotherapy for prostate cancer with adverse pathological features
AU - Hwang, William L.
AU - Tendulkar, Rahul D.
AU - Niemierko, Andrzej
AU - Agrawal, Shree
AU - Stephans, Kevin L.
AU - Spratt, Daniel E.
AU - Hearn, Jason W.
AU - Koontz, Bridget F.
AU - Lee, W. Robert
AU - Michalski, Jeff M.
AU - Pisansky, Thomas M.
AU - Liauw, Stanley L.
AU - Abramowitz, Matthew C.
AU - Pollack, Alan
AU - Moghanaki, Drew
AU - Anscher, Mitchell S.
AU - Den, Robert B.
AU - Zietman, Anthony L.
AU - Stephenson, Andrew J.
AU - Efstathiou, Jason A.
N1 - Funding Information:
reported serving on the advisory board of Dendreon and being a member of the NRG Oncology Genitourinary Core Committee. Dr Koontz reported receiving research funding from Janssen Pharmaceuticals and consulting for Blue Earth Diagnostics, GenomeDx Biosciences, Laguna Pharmaceuticals, and ChanRX. Dr Michalski reported receiving travel accommodations and expenses from Varian Medical Systems, Siemens Healthcare Diagnostics, ViewRay, and General Electric Systems. Dr Abramowitz reported receiving research funding from Elekta, consulting for General Electric Corporation, and being employed by Artech. Dr Pollack reported receiving research funding from GenomeDx Biosciences. Dr Moghanaki reported receiving travel accommodations and expenses from Varian Medical Systems and honoraria from Augmenix and Varian Medical Systems. Dr Den reported receiving research funding from Medivation as well as consulting honoraria for GenomeDx Biosciences and Bayer Healthcare. Dr Stephenson reported consulting for Bayer, receiving research funding from Medivation/Astellas Pharma, and receiving travel accommodations and expenses from Blue Earth and Genomic Health. Dr Efstathiou reported receiving research funding from the Prostate Cancer Foundation and consulting for Medivation/ Astellas, Genentech, Bayer Healthcare, EMD Serono/Pfizer, Blue Earth Diagnostics, and Taris Biomedical. No other disclosures were reported.
Funding Information:
Funding/Support: This work was supported by the Prostate Cancer Foundation.
Publisher Copyright:
© 2018 American Medical Association. All rights reserved.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2018/5
Y1 - 2018/5
N2 - IMPORTANCE Prostate cancer with adverse pathological features (ie, pT3 and/or positive margins) after prostatectomy may be managed with adjuvant radiotherapy (ART) or surveillance followed by early-salvage radiotherapy (ESRT) for biochemical recurrence. The optimal timing of postoperative radiotherapy is unclear. OBJECTIVE To compare the clinical outcomes of postoperative ART and ESRT administered to patients with prostate cancer with adverse pathological features. DESIGN, SETTING, AND PARTICIPANTS This multi-institutional, propensity score–matched cohort study involved 1566 consecutive patients who underwent postprostatectomy ART or ESRT at 10 US academic medical centers between January 1, 1987, and December 31, 2013. Propensity score 1-to-1 matching was used to account for covariates potentially associated with treatment selection. Data were collected from January 1 to September 30, 2016. Data analysis was conducted from October 1, 2016, to October 21, 2017. MAIN OUTCOMES AND MEASURES Freedom from postirradiation biochemical failure, freedom from distant metastases, and overall survival. All outcomes were measured from date of surgery to address lead-time bias. RESULTS Of 1566 patients, 1195 with prostate-specific antigen levels of 0.1 to 0.5 ng/mL received ESRT and 371 patients with prostate-specific antigen levels lower than 0.1 ng/mL received ART. The median age (interquartile range) was 60 (55-65) years. After propensity score matching, the median (interquartile range) follow-up after surgery was similar between the ESRT and ART groups (73.3 [44.9-106.6] months vs 65.8 [40-107] months; P = .22). Adjuvant RT, compared with ESRT, was associated with higher freedom from biochemical failure (12-year actuarial rates: 69% [95% CI, 60%-76%] vs 43% [95% CI, 35%-51%]; effect size, 26%), freedom from distant metastases (95% [95% CI, 90%-97%] vs 85% [95% CI, 76%-90%]; effect size, 10%), and overall survival (91% [95% CI, 84%-95%] vs 79% [95% CI, 69%-86%]; effect size, 12%). Adjuvant RT, lower Gleason score and T stage, nodal irradiation, and postoperative androgen deprivation therapy were favorable prognostic features on multivariate analysis for biochemical failure. Sensitivity analysis demonstrated that the decreased risk of biochemical failure associated with ART remained significant unless more than 56% of patients in the ART group were cured by surgery alone. This threshold is greater than the estimated 12-year freedom from biochemical failure rate of 33% to 52% after radical prostatectomy alone, as determined by a contemporary dynamic nomogram. CONCLUSIONS AND RELEVANCE Adjuvant RT, compared with ESRT, was associated with reduced biochemical recurrence, distant metastases, and death for high-risk patients, pending prospective validation. These findings suggest that a greater proportion of patients with prostate cancer who have adverse pathological features may benefit from postprostatectomy ART rather than surveillance followed by ESRT.
AB - IMPORTANCE Prostate cancer with adverse pathological features (ie, pT3 and/or positive margins) after prostatectomy may be managed with adjuvant radiotherapy (ART) or surveillance followed by early-salvage radiotherapy (ESRT) for biochemical recurrence. The optimal timing of postoperative radiotherapy is unclear. OBJECTIVE To compare the clinical outcomes of postoperative ART and ESRT administered to patients with prostate cancer with adverse pathological features. DESIGN, SETTING, AND PARTICIPANTS This multi-institutional, propensity score–matched cohort study involved 1566 consecutive patients who underwent postprostatectomy ART or ESRT at 10 US academic medical centers between January 1, 1987, and December 31, 2013. Propensity score 1-to-1 matching was used to account for covariates potentially associated with treatment selection. Data were collected from January 1 to September 30, 2016. Data analysis was conducted from October 1, 2016, to October 21, 2017. MAIN OUTCOMES AND MEASURES Freedom from postirradiation biochemical failure, freedom from distant metastases, and overall survival. All outcomes were measured from date of surgery to address lead-time bias. RESULTS Of 1566 patients, 1195 with prostate-specific antigen levels of 0.1 to 0.5 ng/mL received ESRT and 371 patients with prostate-specific antigen levels lower than 0.1 ng/mL received ART. The median age (interquartile range) was 60 (55-65) years. After propensity score matching, the median (interquartile range) follow-up after surgery was similar between the ESRT and ART groups (73.3 [44.9-106.6] months vs 65.8 [40-107] months; P = .22). Adjuvant RT, compared with ESRT, was associated with higher freedom from biochemical failure (12-year actuarial rates: 69% [95% CI, 60%-76%] vs 43% [95% CI, 35%-51%]; effect size, 26%), freedom from distant metastases (95% [95% CI, 90%-97%] vs 85% [95% CI, 76%-90%]; effect size, 10%), and overall survival (91% [95% CI, 84%-95%] vs 79% [95% CI, 69%-86%]; effect size, 12%). Adjuvant RT, lower Gleason score and T stage, nodal irradiation, and postoperative androgen deprivation therapy were favorable prognostic features on multivariate analysis for biochemical failure. Sensitivity analysis demonstrated that the decreased risk of biochemical failure associated with ART remained significant unless more than 56% of patients in the ART group were cured by surgery alone. This threshold is greater than the estimated 12-year freedom from biochemical failure rate of 33% to 52% after radical prostatectomy alone, as determined by a contemporary dynamic nomogram. CONCLUSIONS AND RELEVANCE Adjuvant RT, compared with ESRT, was associated with reduced biochemical recurrence, distant metastases, and death for high-risk patients, pending prospective validation. These findings suggest that a greater proportion of patients with prostate cancer who have adverse pathological features may benefit from postprostatectomy ART rather than surveillance followed by ESRT.
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U2 - 10.1001/jamaoncol.2017.5230
DO - 10.1001/jamaoncol.2017.5230
M3 - Article
C2 - 29372236
AN - SCOPUS:85048735559
VL - 4
JO - JAMA oncology
JF - JAMA oncology
SN - 2374-2437
IS - 5
M1 - 2670381
ER -