Use and duration of androgen suppression therapy with definitive radiotherapy for localized prostate cancer: a meta-analysis of individual patient data

Fund

Randomized trials have investigated various strategies for intensifying androgen deprivation therapy (ADT) in men receiving radiation therapy for the treatment of prostate cancer. This meta-analysis of individual patient data from relevant randomized trials aimed to quantify the benefit of these interventions overall and in clinically relevant subgroups.

Methods

For this meta-analysis, we performed a systematic literature search of MEDLINE, Embase, trials registries, the Web of Science, Scopus and conference proceedings to identify trials with results published in English between 1 January 1962 and December 30, 2020. Multicenter randomized trials were eligible if they evaluated the use or prolongation of ADT (or both) in men with localized prostate cancer receiving definitive radiotherapy, reported or collected data on distant metastasis and survival, and used ADT for a protocol-defined duration. The Meta-Analysis of Randomized Trials in Prostate Cancer Consortium (MARCAP) was consulted to obtain individual patient data from randomized trials. The primary endpoint was metastasis-free survival. Hazard ratios (HR) were obtained using stratified Cox models for the use of ADT (radiation therapy alone vs. radiotherapy plus ADT), neoadjuvant extension ADT (c. –6 months to 18–36 months). Formal interaction tests between interventions and metastasis-free survival were performed for predefined subgroups defined by age, National Comprehensive Cancer Network (NCCN) risk group, and radiation therapy dose. This meta-analysis is registered with PROSPERO, CRD42021236855.

Results

Our search returned 12 eligible trials that provided individual patient data (10,853 patients) with a median follow-up of 11·4 years (IQR 9·0–15·0). Adding ADT to radiotherapy significantly improved metastasis-free survival (HR 0 83 [95% CI 0·77–0·89], p

Interpretation

Our results provide the strongest level of evidence to date on the magnitude of benefit of intensified ADT treatment with radiotherapy for men with localized prostate cancer. Adding ADT and extending the portion of ADT following radiation therapy is associated with improved metastasis-free survival in men regardless of risk group, age, and dose of radiation therapy given ; however, the magnitude of benefit may vary and shared decision-making with patients is recommended.

Funding

University Hospitals Seidman Cancer Center, Prostate Cancer Foundation and American Society for Radiation Oncology.

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