ADT Combinations With Radiation for Prostate Cancer: A Systematic Review and Meta-analysis

There is substantially heterogeneous use of luteinizing hormone-releasing hormone analogs (LHRHa) with or without first-generation nonsteroidal antiandrogens (NSAA, eg, 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, and toxicity.

We performed a systematic search of studies conducted between 1966 and March 2026 evaluating androgen deprivation therapy (ADT) duration, with or without NSAA, when combined with definitive or salvage radiation therapy 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 2 observers. Data were pooled using a random-effects model.

Although prolonging LHRHa duration was associated with improved OS, prolonging NSAA was not (ref 1-2 months; 3-5-month NSAA hazard ratio, 1.54, 95% CI, 0.97-2.44, P = .07; ≥6-month NSAA hazard ratio, 1.68, 95% CI, 1.07-2.63, P = .02). Longer durations of NSAA or LHRHa were not significantly associated with other-cause mortality. Prolonging NSAA duration was associated with higher odds of early ADT discontinuation (ref 0-2-month NSAA; 3-5-month odds ratio, 5.05, 95% CI, 1.21-21.16, P = .03; 6-9 months, 3.97, 95% CI, 0.94-16.67, P = .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 a clear signal that prolonging NSAA was associated with increased toxicity. Providers should consider limiting the duration of NSAA if used in combination with LHRHa.