Hypofractionated radiotherapy for prostate cancer matches conventional treatment outcomes

Men with high-risk prostate cancer have a higher likelihood of having residual disease following prostatectomy and may require radiation therapy after surgery, particularly when PSA levels begin to rise. Conventional postprostatectomy radiotherapy (COPORT) is typically delivered over 37 fractions, while hypofractionated postprostatectomy radiotherapy (HYPORT) delivers a slightly lower total radiation dose over just 25 fractions. Five-year results from the NRG-GU003 study showed that HYPORT and COPORT provided similar patient-reported urinary and bowel outcomes, overall quality of life, and biochemical control. However, HYPORT was associated with a statistically significant increase in physician-reported grade 3 urinary adverse events, particularly cystitis and hematuria. These results were presented during the Clinical Trials Session of the 2026 American Society for Radiation Oncology Annual Meeting in Boston, Massachusetts.

Postoperative radiation is an important part of preserving the opportunity for cure in patients with PSA recurrence after prostatectomy. Traditionally, treatment has required 37 sessions over approximately seven weeks, which can make it difficult for some patients to receive and burdensome for those who do. These findings show that postoperative radiation can be delivered in a shorter five-week course of 25 treatments without compromising long-term cancer control or patient-reported quality of life."

Mark Buyyounouski, MD, MS, FASTRO at Stanford University and lead author, NRG-GU003 manuscript

The Phase III trial accrued 296 eligible patients and stratified them by baseline EPIC urinary and bowel scores and prior androgen deprivation therapy use. Patients were then randomly assigned to either the HYPORT treatment arm receiving 62.5 Gy to the prostate bed in 25 fractions of 2.5 Gy or the COPORT treatment arm receiving 66.6 Gy to the prostate bed in 37 fractions of 1.8 Gy. The primary objective of the study was to determine if HYPORT was noninferior to COPORT regarding patient-reported urinary and bowel symptoms at 2 years. Secondary endpoints of this trial included freedom from biochemical failure, time to progression, local failure, regional failure, salvage therapy, distant metastases, prostate cancer-specific survival, overall survival, and adverse events.

At 5 years, HYPORT was associated with higher rates of grade 3 adverse events compared with COPORT (16% vs. 7%; p=0.02), including grade 3 renal and urinary disorders (13% vs. 3%; p=0.003), driven by higher rates of noninfective cystitis (7% vs. 0%) and hematuria (6% vs. 0.7%). However, there were no grade 4–5 radiation-related adverse events, and time to grade 3 adverse events did not differ between groups (p=0.4). The mean change in patient-reported outcomes from baseline to 5 years were also similar between COPORT and HYPORT for bowel symptoms (0.6 vs. −2.0; p=0.1), urinary symptoms (−5.7 vs. −8.0; p=0.4), and overall quality of life as measured by EQ-5D (−0.01 vs. 0.0; p=0.5). With a median follow-up of 7 years, biochemical failure at 5 years was also similar between COPORT and HYPORT (18% vs. 21%; p=0.3), with 31 total deaths reported, including 4 from prostate cancer.

"While long-term patient-reported urinary outcomes were similar, physician-reported Grade 3 urologic toxicity was increased with hypofractionation. The reason for that difference is unknown. Physician-reported toxicity primarily captures clinical events and the interventions they require, while patient-reported outcomes capture symptoms, function, and how treatment affects patients' daily lives. These measures provide different, complementary perspectives on treatment effects."

He concludes, "Physicians will need to decide how much weight to give the toxicity findings when choosing a fractionation schedule, particularly when a shorter course could improve access to care, reduce treatment burden, or even make postoperative radiation possible."

This project was supported by grants UG1CA189867 (NCORP), U10CA180822 (NRG Oncology SDMC), U10CA180868 (NRG Oncology Operations), and U24CA180803 (IROC) from the National Cancer Institute (NCI), part of National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.