ADT combinations with radiation for prostate cancer: A systematic review and meta-analysis.

Abstract

There is substantially heterogeneous use of luteinizing hormone-releasing hormone analogues (LHRHa) with or without first-generation non-steroidal anti-androgens (NSAA, e.g. bicalutamide) during radiation for localized prostate cancer. The primary objectives of this study were to determine the impact of NSAA on overall survival (OS), other cause mortality (OCM) and toxicity. We performed a systematic search of studies conducted between 1966 and March 2026 evaluating ADT duration, with or without NSAA, when combined with definitive or salvage radiotherapy for localized prostate cancer. Trials including second-generation NSAA, surgical castration, lifelong ADT or intermittent ADT were excluded. PRISMA guidelines were used for abstracting data and assessing data quality and validity, with independent extraction by two observers. Data were pooled using a random-effects model. While prolonging LHRHa duration was associated with improved OS, prolonging NSAA was not (ref 1-2 months; 3-5 months NSAA HR 1.54, 95% CI 0.97, 2.44, p=0.07; ≥6 months NSAA HR 1.68, 95% CI 1.07-2.63, p=0.02). Longer durations of NSAA or LHRHa were not significantly associated with OCM. Prolonging NSAA duration was associated with higher odds of early ADT discontinuation (ref 0-2 months NSAA; 3-5 months OR 5.05, 95% CI 1.21-21.16, p=0.03; 6-9 months 3.97, 95% CI 0.94-16.67, p=0.06), although estimates were imprecise with wide confidence intervals. This meta-analysis demonstrates a lack of OS benefit to prolonging NSAA duration when used with LHRHa. There is some signal that adding NSAA contributes to early ADT discontinuation, but our data did not show clear signal that prolonging NSAA was associated with increased toxicity. Providers should consider limiting the duration of NSAA if used in combination with LHRHa.