BACKGROUND: Intermediate clinical endpoints (ICEs) prognostic for overall survival (OS) are needed for men receiving postprostatectomy radiation therapy (PORT) to improve clinical trial design. OBJECTIVE: To identify a potential ICE for men receiving PORT. DESIGN, SETTING, AND PARTICIPANTS: We performed an institutional review board-approved multi-institutional retrospective study of 566 men consecutively treated with PORT at tertiary care centers from 1986 to 2013. The median follow-up was 8.2 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Biochemical failure (BF), distant metastases (DM), and castrate-resistant prostate cancer (CRPC) were evaluated for correlation with OS and assessed as time-dependent variables in a multivariable Cox proportional hazards model and in landmark analyses at 1, 3, 5, and 7 yr after PORT. Cross-validated concordance (c) indices were used to assess model discrimination. RESULTS AND LIMITATIONS: OS at 1, 3, 5, and 7 yr after PORT was 98%, 95%, 90%, and 82%, respectively. In a time-varying model controlling for clinical and pathologic variables, BF (hazard ratio [HR] 2.32, 95% confidence interval [CI] 1.45-3.71; p<0.001), DM (HR 6.52, 95% CI 4.20-10.1; p<0.001), and CRPC (HR 2.47, 95% CI 1.56-3.92; p<0.001) were associated with OS. In landmark analyses, 5-yr DM had the highest c index when adjusting for baseline covariates (0.78), with 5-yr DM also providing the greatest increase in discriminatory power over a model only including baseline covariates. These findings require validation in prospective randomized data. CONCLUSIONS: While limited by the retrospective nature of the data, 5-yr DM is associated with lower OS following PORT, outperforming the prognostic capability of BF and CRPC at 1, 3, 5, or 7 yr after treatment. Confirmation of this ICE as a surrogate for OS is needed from randomized trial data so that it can be incorporated into future clinical trial design. PATIENT SUMMARY: We assessed potential intermediate clinical endpoints prognostic for overall survival in a cohort of men receiving radiotherapy after prostatectomy. We identified the development of metastatic disease within 5 yr after treatment as the strongest predictor of overall survival.
BACKGROUND: Intermediate clinical endpoints (ICEs) prognostic for overall survival (OS) are needed for men receiving postprostatectomy radiation therapy (PORT) to improve clinical trial design. OBJECTIVE: To identify a potential ICE for men receiving PORT. DESIGN, SETTING, AND PARTICIPANTS: We performed an institutional review board-approved multi-institutional retrospective study of 566 men consecutively treated with PORT at tertiary care centers from 1986 to 2013. The median follow-up was 8.2 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Biochemical failure (BF), distant metastases (DM), and castrate-resistant prostate cancer (CRPC) were evaluated for correlation with OS and assessed as time-dependent variables in a multivariable Cox proportional hazards model and in landmark analyses at 1, 3, 5, and 7 yr after PORT. Cross-validated concordance (c) indices were used to assess model discrimination. RESULTS AND LIMITATIONS: OS at 1, 3, 5, and 7 yr after PORT was 98%, 95%, 90%, and 82%, respectively. In a time-varying model controlling for clinical and pathologic variables, BF (hazard ratio [HR] 2.32, 95% confidence interval [CI] 1.45-3.71; p<0.001), DM (HR 6.52, 95% CI 4.20-10.1; p<0.001), and CRPC (HR 2.47, 95% CI 1.56-3.92; p<0.001) were associated with OS. In landmark analyses, 5-yr DM had the highest c index when adjusting for baseline covariates (0.78), with 5-yr DM also providing the greatest increase in discriminatory power over a model only including baseline covariates. These findings require validation in prospective randomized data. CONCLUSIONS: While limited by the retrospective nature of the data, 5-yr DM is associated with lower OS following PORT, outperforming the prognostic capability of BF and CRPC at 1, 3, 5, or 7 yr after treatment. Confirmation of this ICE as a surrogate for OS is needed from randomized trial data so that it can be incorporated into future clinical trial design. PATIENT SUMMARY: We assessed potential intermediate clinical endpoints prognostic for overall survival in a cohort of men receiving radiotherapy after prostatectomy. We identified the development of metastatic disease within 5 yr after treatment as the strongest predictor of overall survival.
Authors: Kathleen E Houlahan; Yu-Jia Shiah; Alexander Gusev; Jiapei Yuan; Musaddeque Ahmed; Anamay Shetty; Susmita G Ramanand; Cindy Q Yao; Connor Bell; Edward O'Connor; Vincent Huang; Michael Fraser; Lawrence E Heisler; Julie Livingstone; Takafumi N Yamaguchi; Alexandre Rouette; Adrien Foucal; Shadrielle Melijah G Espiritu; Ankit Sinha; Michelle Sam; Lee Timms; Jeremy Johns; Ada Wong; Alex Murison; Michèle Orain; Valérie Picard; Hélène Hovington; Alain Bergeron; Louis Lacombe; Mathieu Lupien; Yves Fradet; Bernard Têtu; John D McPherson; Bogdan Pasaniuc; Thomas Kislinger; Melvin L K Chua; Mark M Pomerantz; Theodorus van der Kwast; Matthew L Freedman; Ram S Mani; Housheng H He; Robert G Bristow; Paul C Boutros Journal: Nat Med Date: 2019-10-07 Impact factor: 53.440
Authors: William C Jackson; Ming Tang; Matthew J Schipper; Howard M Sandler; Zachary S Zumsteg; Jason A Efstathiou; William U Shipley; Wendy Seiferheld; Himanshu R Lukka; Jean-Paul Bahary; Anthony L Zietman; Thomas M Pisansky; Kenneth L Zeitzer; William A Hall; Robert T Dess; Richard D Lovett; Alexander G Balogh; Felix Y Feng; Daniel E Spratt Journal: J Clin Oncol Date: 2022-06-23 Impact factor: 50.717
Authors: Gaëtan Devos; Wout Devlies; Gert De Meerleer; Marcella Baldewijns; Thomas Gevaert; Lisa Moris; Daimantas Milonas; Hendrik Van Poppel; Charlien Berghen; Wouter Everaerts; Frank Claessens; Steven Joniau Journal: Nat Rev Urol Date: 2021-09-15 Impact factor: 14.432
Authors: Kosj Yamoah; Kyung Min Lee; Shivanshu Awasthi; Patrick R Alba; Cristina Perez; Tori R Anglin-Foote; Brian Robison; Anthony Gao; Scott L DuVall; Evangelia Katsoulakis; Yu-Ning Wong; Sarah C Markt; Brent S Rose; Ryan Burri; Carrie Wang; Okoduwa Aboiralor; Angelina K Fink; Nicholas G Nickols; Julie A Lynch; Isla P Garraway Journal: JAMA Netw Open Date: 2022-01-04