Five-year patient-reported outcome data from NRG Oncology GU003, a phase 3 randomized trial, were presented at the ASTRO 2026 Annual Meeting by Mark Buyyounouski, MD, of Stanford University. The trial compared hypofractionated postprostatectomy radiotherapy (HYPORT) with conventionally fractionated postprostatectomy radiotherapy (COPORT) in men with high-risk prostate cancer features following radical prostatectomy.
At five years, no statistically significant differences were observed in patient-reported genitourinary or gastrointestinal outcomes, quality of life, or biochemical failure rates between the two treatment arms. However, physician-reported grade 3 genitourinary adverse events were significantly more common with HYPORT, driven primarily by higher rates of noninfective cystitis and hematuria.
Key finding
Despite a significantly higher rate of physician-reported grade 3 genitourinary adverse events with hypofractionated postprostatectomy radiotherapy compared with conventional fractionation (13% vs. 3%), five-year patient-reported urinary, bowel, and quality-of-life outcomes showed no significant differences between arms, though EPIC questionnaire compliance at five years was only 56%, which limits the strength of these conclusions.
Study Design
| Trial | NRG Oncology GU003 (Phase 3, randomized) |
|---|---|
| Population | 296 men with pT2/3pNX/0 prostate cancer post-prostatectomy; eligible with detectable PSA ≥0.1 ng/mL or undetectable PSA with pT3 disease or pT2 disease with positive surgical margin |
| Treatment | HYPORT: 62.5 Gy to the prostate bed in 25 fractions of 2.5 Gy (n=144) vs. COPORT: 66.6 Gy in 37 fractions of 1.8 Gy (n=152) |
| Primary endpoint | Patient-reported genitourinary and gastrointestinal toxicity at 2 years via the Expanded Prostate Index Composite (EPIC); noninferiority of HYPORT previously demonstrated in the primary analysis |
| Key secondary endpoints | Quality of life (EQ-5D), adverse events, overall survival, prostate cancer-specific survival, biochemical failure (PSA ≥0.4 ng/mL and rising) |
The trial enrolled men at high risk for adverse pathologic features at prostatectomy, including those with Gleason 8–10 disease or MRI-suspected extracapsular extension, a population in which surgery alone is frequently non-curative and postoperative radiotherapy is often required. The five-year results reported here represent longer-term follow-up of a trial whose primary noninferiority finding was previously published at two years. Median follow-up for this analysis was seven years.
Results and Safety
At five years, patient-reported EPIC bowel summary score changes from baseline were 0.6 with COPORT and −2.0 with HYPORT (p=0.1), and EPIC urinary summary score changes were −5.7 with COPORT and −8.0 with HYPORT (p=0.4), with neither difference reaching statistical significance. EQ-5D quality-of-life score changes from baseline were similarly comparable between arms (−0.01 vs. 0.0; p=0.5). EPIC compliance at five years was 56% overall (58% COPORT, 55% HYPORT), and EQ-5D compliance was 51% in both arms; these relatively modest compliance rates should be considered when interpreting the patient-reported findings.
Biochemical failure rates at five years did not differ significantly between arms: 18% with COPORT versus 21% with HYPORT (p=0.3). A total of 31 deaths were reported across both arms (14 COPORT, 17 HYPORT), with four (13%) attributable to prostate cancer. No grade 4 or 5 adverse events related to radiotherapy were reported in either arm. Grade 3 adverse events occurred in 7% of patients receiving COPORT (11 men) and 16% receiving HYPORT (23 men; p=0.02). Grade 3 renal and urinary disorders specifically occurred in 3% with COPORT versus 13% with HYPORT (p=0.003), driven by higher rates of noninfective cystitis (0% vs. 7%) and hematuria (0.7% vs. 6%). One grade 3 urinary tract obstruction (stricture) was reported on the COPORT arm. Time to grade 3 adverse events did not differ between the two arms (p=0.4).
Clinical Context
Conventional postprostatectomy radiotherapy requires 37 fractions — 48% more than the 25-fraction HYPORT regimen studied in GU003. A shorter course offers practical advantages for patients, including reduced travel burden and treatment time. The five-year data from GU003 suggest that the patient-centered benefits of hypofractionation can be preserved without meaningful differences in patient-reported outcomes or disease control, even as physician-reported grade 3 genitourinary toxicity (predominantly cystitis and hematuria) was more frequent with HYPORT. The investigators noted that this toxicity profile was consistent with contemporary series and that the absolute differences in cystitis (7%) and hematuria (5%) did not translate into detectably worse patient-reported outcomes.
Longer-term survival and disease-control data beyond the seven-year median follow-up reported here were not presented, and questions remain about outcomes in specific pathologic subgroups. The relatively low EPIC compliance at five years (56%) is a limitation that may affect the precision of patient-reported outcome comparisons at that timepoint.
Sources
- ASTRO 2026 Annual Meeting. “Five-Year Results of a Phase 3 Trial of Hypofractionated vs. Conventional Postprostatectomy Radiotherapy: NRG Oncology GU003.” Conference abstract and presentation (CT 01 – Clinical Trials Session). Presented September 27, 2026. View source.
AI disclosure: This article was prepared with assistance from generative AI using the source material cited above. It was reviewed and edited by Brandon Twyford before publication.
