To evaluate the safety of moderately hypofractionated radiotherapy to the prostate and pelvic elective nodal irradiation (ENI) with intraprostatic and nodal boost in patients with high-risk prostate cancer.
In this prospective phase 2 single-arm study, patients with high-risk or node-positive prostate cancer received external beam radiotherapy to the prostate and ENI with moderate hypofractionation (60 Gy in 20 fractions to the prostate; 48 Gy ENI) with ADT. Simultaneous integrated boosts were allowed to 68 Gy to intraprostatic gross disease (MRI-defined) and 55 Gy to radiographically-involved nodes. The primary endpoint was acute gastrointestinal (GI) side effects (CTCAE v5.0) at 3 months following radiotherapy, with an a priori hypothesis that acute grade ≥ 2 GI side effects would not exceed 35%. Secondary endpoints included acute genitourinary (GU) side effects and quality of life (QoL) (EPIC-26 and IPSS).
100 patients were enrolled; 97 completed treatment. Median age was 73, 49% had grade group 4-5 disease, median PSA was 22.2 ng/mL, 21% were cN1. 23 (24%) and 18 (19%) of patients received intraprostatic and nodal boosts, respectively. The rate of acute grade ≥ 2 GI side effects was 15.5% (one-sided 95% upper confidence bound22.8%). On univariable analysis, higher rectal and bowel D1cc and intraprostatic boost were significantly associated with increased acute GI side effects. The rate of grade ≥ 2 acute GU side effects was 26.8% (95% CI 18.3-36.8%). There was no statistically significant detriment to mean GI or GU QoL at 3 months post-treatment.
Moderately hypofractionated radiotherapy to the prostate and ENI with boosts to gross disease was associated with lower-than-expected side effects and no statistically significant detriment to patient-reported mean GI or GU QoL at 3 months post-treatment.
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. 2026 May 23 [Epub ahead of print]
John Mohan Mathew, Hannah Bacon, Jeff Winter, Jamie Bernstein, Zhihui Amy Liu, Vickie Kong, Jennifer Dang, Katelyn Wang, Peter Chung, Andrew Bayley, Alejandro Berlin, Charles Catton, Enrique Gutierrez, Aruz Mesci, Andrew McPartlin, Srinivas Raman, Shabbir Alibhai, Edward Taylor, Padraig Warde, Rachel M Glicksman
Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada; Department of Radiation Oncology, Government Medical College, Thiruvananthapuram, Kerala, India., Department of Radiation Oncology, University of Toronto, Toronto, Canada., Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Canada., Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada., Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada. Electronic address: ., Radiation Oncology, BC Cancer, Department of Surgery, The University of British Columbia, Vancouver, Canada., Department of Supportive Care, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada., Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Canada. Electronic address: .