Derya Tilki1,2, Ming-Hui Chen3, Jing Wu4, Hartwig Huland1, Markus Graefen1, Thomas Wiegel5, Dirk Böhmer6, Osama Mohamad7, Janet E Cowan8, Felix Y Feng7,8, Peter R Carroll8, Bruce J Trock9, Alan W Partin10, Anthony V D'Amico11. 1. Martini-Klinik Prostate Cancer Center, University Hospital-Hamburg-Eppendorf, Hamburg, Germany. 2. Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany. 3. Department of Statistics, University of Connecticut, Storrs, CT. 4. Department of Computer Science and Statistics, University of Rhode Island, Kingston, RI. 5. Department of Radio Oncology, University Hospital Ulm, Ulm, Germany. 6. Department of Radiation Oncology, Charité University Hospital, Berlin, Germany. 7. Department of Radiation Oncology, University of San Francisco, San Francisco, CA. 8. Department of Urology, University of San Francisco, San Francisco, CA. 9. Division of Epidemiology, Brady Urological Institute at Johns Hopkins Medical Institution, Baltimore, MD. 10. Department of Urology, Brady Urological Institute at Johns Hopkins Medical Institution, Baltimore, MD. 11. Department of Radiation Oncology, Brigham and Women's Hospital and Dana Farber Cancer Institute, Boston, MA.
Abstract
PURPOSE: Adjuvant compared with early salvage radiation therapy (sRT) following radical prostatectomy (RP) has not been shown to reduce progression-free survival in randomized controlled trials. However, these trials might have missed a benefit in men with adverse pathology at RP given that these men were under-represented and immortal time bias might have been present; herein, we investigate this possibility. METHODS: We evaluated the impact of adjuvant versus early sRT on all-cause mortality (ACM) risk in men with adverse pathology defined as positive pelvic lymph nodes (pN1) or pGleason score 8-10 prostate cancer (PC) and disease extending beyond the prostate (pT3/4). We used a treatment propensity score to minimize potential treatment selection bias when estimating the causal effect of adjuvant versus early sRT on ACM risk and a sensitivity analysis to assess the impact that varying definitions of adverse pathology had on ACM risk adjusting for age at RP, PC prognostic factors, site, and the time-dependent use of post-RP androgen deprivation therapy. RESULTS: After a median follow-up (interquartile range) of 8.16 (6.00-12.10) years, of the 26,118 men in the study cohort, 2,104 (8.06%) died, of which 539 (25.62%) were from PC. After excluding men with a persistent prostate-specific antigen, adjuvant compared with early sRT was associated with a significantly lower ACM risk among men with adverse pathology at RP when men with pN1 PC were excluded (0.33 [0.13-0.85]; P = .02) or included (0.66 [0.44-0.99]; P = .04). CONCLUSION: Adjuvant radiation therapy should be considered in men with pN1 or pGleason score 8 to 10 and pT3/4 PC given the possibility that a significant reduction in ACM risk exists.
PURPOSE: Adjuvant compared with early salvage radiation therapy (sRT) following radical prostatectomy (RP) has not been shown to reduce progression-free survival in randomized controlled trials. However, these trials might have missed a benefit in men with adverse pathology at RP given that these men were under-represented and immortal time bias might have been present; herein, we investigate this possibility. METHODS: We evaluated the impact of adjuvant versus early sRT on all-cause mortality (ACM) risk in men with adverse pathology defined as positive pelvic lymph nodes (pN1) or pGleason score 8-10 prostate cancer (PC) and disease extending beyond the prostate (pT3/4). We used a treatment propensity score to minimize potential treatment selection bias when estimating the causal effect of adjuvant versus early sRT on ACM risk and a sensitivity analysis to assess the impact that varying definitions of adverse pathology had on ACM risk adjusting for age at RP, PC prognostic factors, site, and the time-dependent use of post-RP androgen deprivation therapy. RESULTS: After a median follow-up (interquartile range) of 8.16 (6.00-12.10) years, of the 26,118 men in the study cohort, 2,104 (8.06%) died, of which 539 (25.62%) were from PC. After excluding men with a persistent prostate-specific antigen, adjuvant compared with early sRT was associated with a significantly lower ACM risk among men with adverse pathology at RP when men with pN1 PC were excluded (0.33 [0.13-0.85]; P = .02) or included (0.66 [0.44-0.99]; P = .04). CONCLUSION: Adjuvant radiation therapy should be considered in men with pN1 or pGleason score 8 to 10 and pT3/4 PC given the possibility that a significant reduction in ACM risk exists.
Authors: Giuseppe Ferrera; Salvatore D'Alessandro; Francesco Cuccia; Vincenzo Serretta; Giovanna Trapani; Gianfranco Savoca; Gianluca Mortellaro; Antonio Lo Casto Journal: J Cancer Res Clin Oncol Date: 2021-09-30 Impact factor: 4.553