Ultra-hypofractionation (UHF) has emerged as a safe and effective strategy; however, its role in prostate cancer (PCa) pelvic nodal irradiation combined with high-dose-rate brachytherapy (HDR-BT) and androgen deprivation therapy (ADT) remains insufficiently defined. PCS-XI (NCT05820633) is a multicentre, phase III randomized trial evaluating pelvic UHF versus conventionally fractionated (CF) radiotherapy. We report a prespecified interim analysis focusing on toxicity and patient-reported outcomes (PROs).
Men with unfavorable-intermediate to very-high-risk prostate adenocarcinoma were enrolled. Patients were randomized 1:1 to CF (43 Gy/20 fractions, 44 Gy/22 fractions, or 46 Gy/23 fractions) or UHF (25 Gy in 5 fractions delivered every other day) whole pelvis radiotherapy, combined with single-fraction 15 Gy HDR-BT to the prostate with concomitant ADT. Genitourinary and gastrointestinal toxicities (CTCAE v5.0) and PROs (IPSS, SHIM, EPIC-26) were collected longitudinally.
At interim analysis, 142 patients were randomized (CF = 73; UHF = 69), with a median follow-up of 17.6 months. Baseline clinicopathologic characteristics, ADT exposure, and treatment volumes were well balanced between arms. Grade 2-3 GU and GI toxicity rates were low and comparable between arms. No grade 4-5 toxicities were observed. Longitudinal PRO analyses demonstrated parallel trajectories. Clinically meaningful differences favoring UHF were observed for urinary incontinence at 12 months and bowel function at 18 months. Conversely, the CF arm demonstrated superior early hormonal function at 3 and 9 months.
Pelvic UHF combined with HDR-BT and ADT was well tolerated compared to CF. These findings support its short-term safety and tolerability. Longer follow-up is required to prove non-inferiority and assess oncologic outcomes.
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. 2026 May 13 [Epub ahead of print]
François Fabi, Juanita Crook, Marjory Jolicoeur, Sarah Rauth, Wayne Koll, Steven Tisseveransinghe, Annie Ebacher, Tamim Niazi, Danny Duplan, Andrée-Anne Bernard, Peter Vavassis, William Foster, Éric Vigneault, Louis Archambault, Luc Beaulieu, Marie-Claude Lavallée, Frédéric Lacroix, Damien Carignan, André-Guy Martin
Radiation Oncology Service, Department of Specialized Medicine, Centre Intégré de Cancérologie (CIC), Hôpital de l'Enfant-Jésus, Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Québec, QC, Canada; Service of Medical Physics and Radioprotection, CHU de Québec-Université Laval, Québec, QC, Canada., Department of Radiation Oncology, BC Cancer- Kelowna, Kelowna, BC, Canada., Department of Oncology, Division of Radiation Oncology, Hôpital Charles LeMoyne, Greenfield Park, QC, Canada., Department of Radiation Oncology, Carlo Fidani Peel Regional Cancer Centre, Mississauga, ON, Canada., Department of Radiation Oncology, RS McLaughlin Durham Regional Cancer Centre, Lakeridge Health, Oshawa, ON, Canada., Department of Oncology, Division of Radiation Oncology, Hôpital Gatineau, Gatineau, QC, Canada., Department of Oncology, Division of Radiation Oncology, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada., Department of Oncology, Division of Radiation Oncology, Jewish General Hospital, McGill University, QC, Canada., Division of Radiation Oncology, Hôpital Cité de-de-la-Santé, Laval, QC, Canada., Radiation Oncology Service, CISSS du Bas-Saint-Laurent, Rimouski, QC, Canada., Department of Oncology, Division of Radiation Oncology, Hôpital Maisonneuve-Rosemont, Montreal, QC, Canada., Radiation Oncology Service, Department of Specialized Medicine, Centre Intégré de Cancérologie (CIC), Hôpital de l'Enfant-Jésus, Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Québec, QC, Canada; Research Center of the CHU de Québec-Université Laval, Axe Oncologie, Québec, QC, Canada., Service of Medical Physics and Radioprotection, CHU de Québec-Université Laval, Québec, QC, Canada; Research Center of the CHU de Québec-Université Laval, Axe Oncologie, Québec, QC, Canada., Service of Medical Physics and Radioprotection, CHU de Québec-Université Laval, Québec, QC, Canada., Research Center of the CHU de Québec-Université Laval, Axe Oncologie, Québec, QC, Canada., Radiation Oncology Service, Department of Specialized Medicine, Centre Intégré de Cancérologie (CIC), Hôpital de l'Enfant-Jésus, Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Québec, QC, Canada; Research Center of the CHU de Québec-Université Laval, Axe Oncologie, Québec, QC, Canada. Electronic address: .