A recent individual patient data (IPD) meta-analysis of randomized trials found a limited overall survival (OS) and metastasis-free survival (MFS) benefit to the addition of hormonal therapy (HT) to postoperative radiotherapy for prostate cancer in patients with pre-radiotherapy prostate-specific antigen (PSA) ≤0. 5 ng/ml. We evaluated whether the OS and MFS benefits of adding HT might be significantly modified by an increasing count of adverse pathological features (adverse feature count [AFC]).
We obtained IPD from five randomized phase 3 trials of postoperative radiotherapy ± HT. AFC was prospectively defined as the sum (0-4) of grade group 4-5 disease, seminal vesicle invasion, positive surgical margins, and extracapsular extension. Intention-to-treat one-stage meta-analytical models were used. We also evaluated the interaction of the benefit of HT with a restricted score comprising only GG4-5 and seminal vesicle invasion (range 0-2), as a pre-specified sensitivity analysis.
We included IPD from 4781 patients with a median follow-up of 9.1 yr. AFC was independently prognostic for OS and MFS. However, AFC did not significantly modify the OS benefit of HT (interaction hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.79-1.10; p = 0.4) or MFS benefit (interaction HR, 0.88; 95% CI, 0.77-1.01; p = 0.08). Results were similar when AFC was analyzed categorically and in high-risk subsets, and when the restricted AFC score was used.
Overall, the data suggest that although adverse pathological features are prognostic, they do not appear predictive of HT benefit after postoperative radiotherapy, which is relevant for patients with a PSA ≤0.5 ng/ml before radiation.
European urology. 2026 Jul 28 [Epub ahead of print]
Amar U Kishan, Yilun Sun, Christopher C Parker, Paul Sargos, Matthew Sydes, Sylvie Chabaud, Meryem Brihoum, Stephane Supiot, Igor Latorzeff, Stephane Guerif, Tahmineh Romero Kalbasi, Michael L Steinberg, Luca F Valle, Kekoa Taparra, Matthew J Farrell, Jonathan E Shoag, Jorge A Garcia, Jason R Brown, Matthew B Rettig, Adam E Singer, Nikita Baclig, Robert E Reiter, Scott Eggener, Wayne Brisbane, Soumyajit Roy, Angela Y Jia, Ting Martin Ma, Nicholas G Nickols, Jason A Efstathiou, 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., Institut de Cancérologie de l'Ouest, Saint Herblain, Nantes, France., Radiation Deparment Onco-Urology and BrainClinque Pasteur, Groupe Orion1 rue de la petite vitesse, 31300 Toulouse, France., Centre Hospitalier Universitaire de Poitiers, Poitiers. 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 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, Oregon Health and Sciences University, Portland, Oregon, 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.