Conditional Prostate Cancer-Specific Survival Probabilities in Recurrent Prostate Cancer Patients Receiving Radiation ± Antiandrogen Therapy: Secondary Analysis of a Randomized Clinical Trial

Abstract

Salvage radiation therapy (SRT) and androgen-deprivation therapy (ADT) are routinely used in patients with elevated prostate-specific antigen (PSA) levels after radical prostatectomy (RP) for prostate cancer (PCa). Although prostate cancer-specific survival (PCSS) following SRT is useful when counseling patients at the time of treatment, the utility of this data from time of diagnosis diminishes over time. Conditional survival (CS) can provide more relevant estimates, especially given long-term PCa survivorship. The primary aim of this study was to analyze CS estimates for recurrent PCa patients undergoing SRT ± ADT. The secondary objective was to determine if factors prognostic of PCSS at diagnosis remain relevant in survivorship. We analyzed data from 760 post-RP patients enrolled in NRG/RTOG 9601 (1998-2003). Eligible patients included men who had undergone prior RP and had pT2/T3 disease without nodal involvement and detectable PSA levels of 0.2-4.0 ng/mL. Patients were randomly assigned to undergo SRT and receive either 24 mo of ADT or placebo. OS was calculated (Kaplan-Meier), cumulative incidence was used to estimate PCSS rates, and prognostic factors associated with PCSS were analyzed by multivariable Cox proportional hazards modeling (MVA). Patients were followed for a median of 13 y. The 5- and 10-y PCSS estimates from diagnosis were 98.52% and 92.7%, respectively. At 1- (n = 755), 3- (n = 727), 5- (n = 680), and 8-y (n = 602) survivorship, chances of PCSS at an additional 5-y were 97.41%, 95.29%, 93.76%, and 91.04%, respectively. On MVA at diagnosis, omission of ADT (HR 2.156, P = 0.0003), increasing age (HR 1.833, P = 0.03), Gleason score (GS) 7 (HR 2.356, P = 0.0057), and GS 8-10 (HR 4.841, P < 0.0001) were associated with PCa-specific mortality. For those who achieved survivorship at 1-, 3-, 5-, and 8-y, all variables remained prognostic of PCa-specific mortality on MVA. Conditional risk of death from PCa for patients treated with SRT increases over time. The initial risk of dying from PCa over a given period, however, is higher than if already having survived a portion of that period. ADT, younger age, and lower GS continue to confer a reduced risk of PCa-specific mortality for long-term survivors. This data can be used to inform survivorship care planning, giving patients more relevant prognostic information during continued surveillance after completion of treatment.