Hormone therapy use and duration with postoperative radiotherapy for recurrent prostate cancer: an individual patient data meta-analysis.

[BACKGROUND] Adding hormone therapy to definitive radiotherapy in localised prostate cancer improves overall survival, but whether it similarly improves overall survival in the context of postoperative radiotherapy (PORT) after radical prostatectomy is unclear. Herein, we report an individual patient data (IPD) meta-analysis of randomised trials aimed at quantifying the benefit of adding hormonal therapy to PORT.

[METHODS] This was an IPD meta-analysis that identified randomised, phase 3 trials of PORT with or without hormone therapy. A systematic literature search of MEDLINE, Embase, trial registries, the Web of Science, Scopus, and relevant conference proceedings was done on Dec 15, 2024. IPD were available via the MARCAP consortium. The primary outcome was overall survival. Meta-analyses evaluated the benefit of adding hormone therapy, short-term hormone therapy (4-6 months), or long-term hormone therapy (24 months) to PORT. Tests for interaction based on pre-PORT prostate-specific antigen (PSA) and duration of hormone therapy were evaluated and non-linear associations between pre-PORT PSA and overall survival were modelled. This study was done under the master protocol of the MARCAP Consortium (PROSPERO registration CRD42019134376).

[FINDINGS] IPD were available for six randomised trials including 6057 patients with a median follow-up of 9·0 years (IQR 7·2-10·7 years). Adding hormone therapy to radiotherapy did not significantly improve overall survival (hazard ratio [HR] 0·87, 95% CI 0·76-1·01, p=0·06). There was no significant interaction between hormone therapy duration and this effect (p=0·17), although there was a significant interaction with pre-PORT PSA greater than 0·5 ng/mL versus 0·5 ng/mL or less (p=0·02). For all pre-PORT PSA values, the upper bounds of the 95% CI of the HR for overall survival crossed 1·0 for patients randomly assigned to PORT with or without short-term hormone therapy (n=3938). For patients randomly assigned to PORT with or without long-term hormone therapy (n=1088), the upper bounds of the 95% CI for overall survival HR fell below 1·0 at PSA greater than 1·6 ng/mL.

[INTERPRETATION] Our findings, we believe, provide the strongest level of evidence to date suggesting there might be no meaningful overall survival benefit to adding hormone therapy, either short-term or long-term hormone therapy, to PORT for PSA 0·5 ng/mL or less, with no apparent difference in efficacy for short-term versus long-term hormone therapy. There is an unmet need to identify biomarkers to predict potential hormone therapy benefit.

[FUNDING] National Institutes of Health.