Faculty Collaboration Database

Optimal Duration of Androgen Deprivation Therapy With Definitive Radiotherapy for Localized Prostate Cancer: A Meta-Analysis. JAMA Oncol 2026 Jan 01;12(1):58-65

Date

11/20/2025

Pubmed ID

41264309

Pubmed Central ID

PMC12635924

DOI

10.1001/jamaoncol.2025.4800

Scopus ID

2-s2.0-105023283707 (requires institutional sign-in at Scopus site)   8 Citations

Abstract

IMPORTANCE: 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.

OBJECTIVE: To determine the ideal duration of ADT for patients with prostate cancer treated with radiotherapy.

DATA SOURCES: 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.

STUDY SELECTION: 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.

DATA EXTRACTION AND SYNTHESIS: 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.

MAIN OUTCOMES AND MEASURES: 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.

RESULTS: 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.

CONCLUSIONS AND RELEVANCE: 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.

Author List

Zaorsky NG, Sun Y, Nabid A, Zapatero A, Bolla M, Joseph D, Maingon P, Guerrero A, Gonzalez AA, San-Segundo CG, Cabeza Rodríguez MÁ, Sole JM, Olivé AP, Steigler A, Souhami L, Carrier N, Armstrong JG, Gillham C, Pisansky TM, Schipper M, Sandler HM, Efstathiou JA, Lawton C, de Reijke TM, Attard G, Roy S, Morgan SC, Malone S, Hall WA, Nguyen PL, Shoag JE, Vince RA Jr, Calaway A, Garcia JA, Barata PC, Mendiratta P, Brown JR, Valle L, Rettig M, Dess RT, Jackson WC, Martin T, Jia AY, Steinberg M, Romero T, Kishan AU, Spratt DE

Authors

William Adrian Hall MD Chair, Professor in the Radiation Oncology department at Medical College of Wisconsin
Colleen A. Lawton MD Emeritus Professor in the Radiation Oncology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aged
Androgen Antagonists
Clinical Trials, Phase III as Topic
Humans
Male
Prostatic Neoplasms
Randomized Controlled Trials as Topic
Time Factors
Treatment Outcome