Anti-Androgen Therapy Overcomes the Time Delay in Initiation of Salvage Radiation Therapy and Rescues the Oncological Outcomes in Men with Recurrent Prostate Cancer After Radical Prostatectomy: A Post Hoc Analysis of the RTOG-9601 Trial Data.

Abstract

BackgroundIt is unknown whether the addition of anti-androgen therapy (AAT) to late salvage radiation therapy (sRT) can lead to oncological outcomes equivalent to that of early sRT in men with recurrent prostate cancer (CaP) after surgery.MethodsData on 670 men who participated in the Radiation Therapy Oncology Group (RTOG)-9601 trial and who experienced biochemical recurrence were extracted using the National Clinical Trials Network (NCTN) data archive platform. Patients were stratified into four treatment groups: early sRT (pre-sRT prostate-specific antigen [PSA] < 0.7 ng/mL) and late sRT (pre-sRT PSA ≥ 0.7 ng/mL) with/without concomitant AAT, based on cut-offs reported in the original trial. Time-varying Cox proportional hazards and Fine–Gray competing-risk regression analyses assessed the adjusted hazards of overall mortality, CaP-specific mortality, and metastasis among the four treatment groups.ResultsAt 15-years (median follow-up of 14.7 years), for patients treated with early sRT, early sRT with AAT, late sRT, and late sRT with AAT, the overall mortality, CaP-specific mortality, and metastasis rates were 22.9, 22.8, 40.1, and 22.9% (log-rank p = 0.0039), 12.1, 3.9, 22.7, and 8.0% (Gray’s p = 0.0004), and 18.8, 14.6, 35.9, and 19.5% (Gray’s p = 0.0004), respectively. Time-varying multivariable adjusted analysis demonstrated increased hazards of overall mortality in patients receiving delayed sRT versus early sRT (hazards ratio [HR] 1.49, 95% confidence interval [CI] 1.02–2.17); however, no difference remained after the addition of concomitant AAT to late sRT (HR 0.85, 95% CI 0.55–1.32, referent early sRT). Likewise, the hazards of cancer-specific mortality and metastatic progression were worse for late sRT when compared with early sRT, but were no different after the addition of AAT to late sRT.ConclusionsPoorer outcomes associated with late sRT in men with recurrent CaP may be rescued by delivery of concomitant AAT.