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

Abstract

Introduction: 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 radiotherapy for the subset of patients with intermediate-risk prostate cancer (IR-PCa). However, due to inclusion criteria, several studies such as NRG/RTOG 0815, GETUG-14, and DFCI 95-096 were excluded. Thus, we conduct the present analysis, inclusive of all studies to define the current role for ST-ADT in IR-PCa.

Methods: A systematic review was conducted of phase III RCTs published or presented between 1/1980 and 10/2024 which profiled the comparative efficacy of radiotherapy ± 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 utilized to explore trial-level factors associated with treatment effects. Synthetic individual patient-level OS data was pooled for confirmation and used to estimate the relative and absolute survival benefit.

Results: Seven RCTs (NRG/RTOG 9408, DFCI 95-096, TROG 96.01, PCS III, EORTC 22991, NRG/RTOG 0815, and GETUG-14) reporting outcomes of 6,279 patients were identified. The pooled HR_OS, HR_BF, and HR_BF+bPFS were 0.88 (95% confidence interval [CI]: 0.79-0.97; p = 0.01), 0.50 (95% CI: 0.37-0.68; p<0.001), and 0.54 (95% CI: 0.46-0.65; p<0.001), 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<0.05) but not for OS (all p>0.05). 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 = 0.021), corresponding to an absolute survival benefit of 5% benefit at 10 years.

Conclusion: The present analysis confirms current knowledge that ST-ADT improves both OS and PSA-based outcomes for unselected patients with IR-PCa to a clinically significant degree.