The Benefit of Short-Term Androgen Deprivation Therapy with Radiation Therapy for Intermediate-Risk Prostate Cancer.

Abstract

A previous, individual patient-level meta-analysis of randomized controlled trials (RCTs) demonstrated the overall survival (OS) benefit of short-term androgen deprivation therapy (ST-ADT) when delivered with radiation therapy (RT) for the subset of patients with intermediate-risk prostate cancer (IR-PCa). However, because of inclusion criteria, several studies such as NRG/RTOG 0815, GETUG-14, and DFCI 95-096 were excluded. Thus, we conducted the present analysis, inclusive of all studies to define the current role of ST-ADT in IR-PCa. A systematic review was conducted of phase 3 RCTs published or presented between January 1980 and October 2024 which profiled the comparative efficacy of radiation therapy ± ST-ADT in patients with IR-PCa. A study-level, random-effects meta-analysis was performed. The primary endpoint of this meta-analysis was OS, with secondary endpoints of time-to-biochemical failure (BF) ± biochemical-progress-free survival (bPFS). Meta-regression was used to explore trial-level factors associated with treatment effects. Synthetic individual patient-level OS data were pooled for confirmation and used to estimate the relative and absolute survival benefit. Seven RCTs (NRG/RTOG 9408, DFCI 95-096, TROG 96.01, PCS III, EORTC 22991, NRG/RTOG 0815, and GETUG-14) reporting outcomes of 6179 patients were identified. The pooled hazard ratios (HRs) for HR_OS, HR_BF, and HR_BF+_bPFS were 0.88 (95% confidence interval [CI], 0.79-0.97; P = .01), 0.50 (95% CI, 0.37-0.68; P < .001), and 0.54 (95% CI, 0.46-0.65; P < .001), respectively. ST-ADT duration, RT dose, and Gleason score trial population composition were each associated with an increased benefit of ST-ADT for biochemical disease control (all P < .05) but not for OS (all P > .05). Pooling of simulated, patient-level data confirmed the presence of a survival benefit (HR_OS, 0.85 [95% CI, 0.76-0.96], log-rank P = .021), corresponding to an absolute survival benefit of 5% benefit at 10 years. The present analysis confirms current knowledge that ST-ADT improves both OS and prostate-specific antigen-based outcomes for unselected patients with IR-PCa to a clinically significant degree.