Abstract

e17115

Background: The survival benefit of adding androgen deprivation therapy (ADT) to radiotherapy for intermediate- and high-risk localized prostate cancer (PCa) was established in trials conducted before the widespread adoption of contemporary image guidance, hypofractionation, and stereotactic ablative radiotherapy (SABR). As SABR enables delivery of high biological doses with improved precision, the incremental oncologic contribution of ADT in the SABR era is increasingly uncertain. This question is particularly relevant for older patients, who frequently have comorbidities and competing mortality risks, where ADT-related sexual, metabolic, and quality-of-life toxicities may outweigh potential benefit and may plausibly worsen overall health status. Methods: We conducted a prospective matched cohort study of men with intermediate- and high-risk localized PCa treated with SABR (35 Gy in 5 fractions) with or without ADT between 2018 and 2024. For each patient receiving SABR+ADT, a contemporaneous SABR-alone patient was matched based on NCCN risk group, baseline PSA, age, and treatment year. Thirty-nine matched pairs were included; mean age was 70.6 years and median follow-up was 42 months. Biochemical recurrence (BCR) was defined per Phoenix criteria. Time-to-event outcomes were analyzed using Kaplan-Meier, log-rank, and stratified Cox models; toxicities were collected retrospectively from medical records. Results: BCR occurred in 5 patients treated with SABR+ADT and 4 patients treated with SABR alone. BCR-free survival did not differ significantly between groups (log-rank p = 0.13). In a stratified Cox model, omission of ADT did not increase the risk of BCR (HR 1.47; 95% CI 0.59–3.64; p = 0.41). Patterns of recurrence were similar across risk categories (HR: 3 vs 3; UIR: 2 vs 1). One SABR-alone patient developed a solitary bone metastasis that was successfully treated with ablative SABR. No prostate cancer-specific deaths occurred in either cohort. Unrelated mortality was 4 vs 2, and loss to follow-up was 4 vs 1 (ADT vs no ADT). Treatment-related toxicity was reported in 28/39 ADT-treated patients, including sexual dysfunction, fatigue, and metabolic adverse effects. No clinically meaningful toxicity was observed with SABR alone. Conclusions: In this prospective matched cohort of predominantly older men treated with SABR for intermediate- and high-risk localized PCa, omission of ADT was not associated with worse biochemical outcomes while avoiding substantial toxicity. Given the comorbidity burden and competing mortality risks common in this population, routine ADT use may represent avoidable harm for selected patients, whereas SABR alone may preserve cancer control with a more favorable tolerability profile. These findings support individualized, risk-adapted ADT use in the SABR era and justify larger prospective studies to refine patient selection.