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.
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).
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 (pinteraction=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 (pinteraction=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.
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.
National Institutes of Health.
Lancet (London, England). 2026 Feb 26 [Epub ahead of print]
Amar U Kishan, Yilun Sun, Christopher C Parker, Paul Sargos, Matthew R Sydes, Sylvie Chabaud, Meryem Brihoum, Tahmineh Romero Kalbasi, Michael L Steinberg, Luca F Valle, Kekoa Taparra, Jonathan E Shoag, Jorge A Garcia, Jason R Brown, Matthew B Rettig, Adam E Singer, Robert E Reiter, Scott Eggener, Wayne Brisbane, Soumyajit Roy, Nicholas G Zaorsky, Angela Y Jia, Ting Martin Ma, Nicholas G Nickols, Jason A Efstathiou, Osama Mohamad, James J Dignam, Wendy F Seiferheld, Alan Pollack, Howard M Sandler, Paul L Nguyen, Pascal Pommier, Daniel E Spratt
Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: ., Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA., The Royal Marsden NHS Foundation Trust, London, UK; The Institute of Cancer Research, London, UK., Institut Bergonié, Bordeaux, France., MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK., Clinical Research Department, Centre Léon Bérard, Lyon, France., Unicancer, Paris, France., Department of Medicine Statistical Core, University of California, Los Angeles, Los Angeles, CA, USA., Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, USA., Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, USA; School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA., Department of Urology, University Hospitals Seidman Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Department of Medicine, University Hospitals Seidman Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA., Department of Urology, University of California, Los Angeles, Los Angeles, CA, USA., Department of Radiation Oncology, University of Washington, Seattle, WA, USA., Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, USA; Department of Radiation Oncology, Greater Los Angeles VA, Los Angeles, CA, USA., Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Department of Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA; Department of American University of Beirut, Beirut, Lebanon., Department of Public Health Sciences, University of Chicago, Chicago, IL, USA; NRG Oncology Statistics and Data Management Center, Philadelphia, PA., NRG Oncology Statistics and Data Management Center, Philadelphia, PA., Department of Radiation Oncology, Miller School of Medicine and Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA., Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Department of Radiation Oncology, Brigham and Women's Hospital and Dana Farber Cancer Institute, Boston, MA, USA., Clinical Research Department, Centre Léon Bérard, Lyon, France; Department of Radiotherapy, Institut Curie, Paris, France.