It remains unknown whether or not short-term androgen deprivation (STAD) improves survival among men with intermediate-risk prostate cancer (IRPC) treated with dose-escalated radiotherapy (RT).

The NRG Oncology/Radiation Therapy Oncology Group 0815 study randomly assigned 1,492 patients with stage T2b-T2c, Gleason score 7, or prostate-specific antigen (PSA) value >10 and ≤20 ng/mL to dose-escalated RT alone (arm 1) or with STAD (arm 2). STAD was 6 months of luteinizing hormone-releasing hormone agonist/antagonist therapy plus antiandrogen. RT modalities were external-beam RT alone to 79.2 Gy or external beam (45 Gy) with brachytherapy boost. The primary end point was overall survival (OS). Secondary end points included prostate cancer-specific mortality (PCSM), non-PCSM, distant metastases (DMs), PSA failure, and rates of salvage therapy.

Median follow-up was 6.3 years. Two hundred nineteen deaths occurred, 119 in arm 1 and 100 in arm 2. Five-year OS estimates were 90% versus 91%, respectively (hazard ratio [HR], 0.85; 95% CI, 0.65 to 1.11]; = .22). STAD resulted in reduced PSA failure (HR, 0.52; <.001), DM (HR, 0.25; <.001), PCSM (HR, 0.10; = .007), and salvage therapy use (HR, 0.62; = .025). Other-cause deaths were not significantly different ( = .56). Acute grade ≥3 adverse events (AEs) occurred in 2% of patients in arm 1 and in 12% for arm 2 ( <.001). Cumulative incidence of late grade ≥3 AEs was 14% in arm 1 and 15% in arm 2 ( = .29).

STAD did not improve OS rates for men with IRPC treated with dose-escalated RT. Improvements in metastases rates, prostate cancer deaths, and PSA failures should be weighed against the risk of adverse events and the impact of STAD on quality of life.