Optimal Duration of Androgen Deprivation Therapy With Definitive Radiotherapy for Localized Prostate Cancer: A Meta-Analysis.

Abstract

The ideal duration of androgen deprivation therapy (ADT) for treating localized prostate cancer is unknown due to variable adherence and treatment durations tested in clinical trials. To determine the ideal duration of ADT for patients with prostate cancer treated with radiotherapy. This individual patient data meta-analysis of 13 randomized phase 3 clinical trials evaluated the use of radiotherapy alone or with ADT. It included patients with a median follow-up of 11.3 (IQR, 9.5-14.5) years and ADT duration of 0 to 36 months. Most patients (7392 [72%]) included had National Comprehensive Cancer Network high-risk or very high-risk disease. For this meta-analysis, a systematic literature search from 1980 to 2020 was performed in trial registries (Cochrane Central Register of Controlled Trials and ClinicalTrials.gov), MEDLINE (1966-2020), Embase (1982-2020), Web of Science, and Scopus to identify trials. Intention-to-treat and as-treated analyses were performed. The number needed to treat to prevent 1 distant metastasis at 10 years was calculated based on prognostic risk group. The analyses were conducted from January 5 to August 15, 2023. The primary end point for this study was overall survival, defined as time to death or last follow-up from randomization. Secondary end points included biochemical recurrence, distant metastasis (DM), prostate cancer-specific mortality, and other-cause mortality. The median (IQR) age among the 10 266 male patients was 70 (65-74) years. Longer durations of ADT were associated with nonlinear improvement in relative benefits of DM, prostate cancer-specific mortality, and overall survival, with reduced estimated benefits beyond 9 to 12 months of ADT based on the end point. There was a near-linear increase in other-cause mortality associated with long-term ADT use (hazard ratio, 1.28; 95% CI, 1.09-1.50; P = .002 for 28 vs 0 months of ADT). The optimal ADT duration based on 10-year DM was 0, 6, 12 months, and undefined for patients with 1 intermediate-risk factor, 2 or more intermediate-risk factors, and National Comprehensive Cancer Network high-risk and very high-risk disease, respectively. The results of this meta-analysis suggest that, for men with localized prostate cancer treated with definitive radiotherapy and ADT, there are relative and absolute benefits from increasing durations of ADT that help provide individualized risk estimates.