NRG-GU003 Trial Compares Hypofractionated vs Conventional Postprostatectomy Radiotherapy for Prostate Cancer

Five-year results from the Phase III NRG-GU003 clinical trial demonstrate that hypofractionated postprostatectomy radiotherapy (HYPORT)—delivering a shorter 25-fraction course of radiation—achieves biochemical control and patient-reported quality-of-life outcomes comparable to conventional postprostatectomy radiotherapy (COPORT) across 37 fractions for men with prostate cancer recurrence.

For men facing biochemical recurrence after a prostatectomy, postoperative radiation therapy represents a vital window to achieve disease control. Traditionally, this intervention requires 37 separate treatment sessions spanning roughly seven weeks. This extended timeline creates significant logistical hurdles and treatment fatigue for patients. The NRG-GU003 trial evaluated whether condensing this regimen could alleviate patient burden without sacrificing clinical efficacy.

In Plain English: What the Data Shows for Patients

• Shorter Schedules: Hypofractionated radiation delivers a total dose over 25 treatments instead of 37, cutting the overall treatment timeline down to approximately five weeks.
• Equal Cancer Control: Five-year follow-up data confirms that long-term cancer containment and overall quality of life remain comparable between the two schedules.
• Increased Short-Term Toxicity: Physician-reported grade 3 urinary side effects were notably higher in the shorter treatment arm, requiring careful clinical monitoring.

Trial Design and Comparative Dosimetry in NRG-GU003

The Phase III trial accrued 296 eligible patients, stratifying them based on baseline Expanded Prostate Cancer Index Composite (EPIC) urinary and bowel scores alongside prior androgen deprivation therapy use. Investigators randomly assigned participants to one of two distinct treatment arms. The HYPORT arm delivered a total dose of 62.5 Gy to the prostate bed using 25 fractions of 2.5 Gy each. Conversely, the COPORT arm administered 66.6 Gy to the prostate bed across 37 fractions of 1.8 Gy each.

The primary objective was establishing whether the hypofractionated schedule was noninferior to conventional dosing regarding patient-reported urinary and bowel symptoms at the two-year mark. Secondary endpoints tracked biochemical failure, time to disease progression, local and regional failure rates, salvage therapy requirements, distant metastases, and overall survival.

Clinical Parameter	HYPORT Arm (25 Fractions)	COPORT Arm (37 Fractions)	Statistical Significance
Total Dose to Prostate Bed	62.5 Gy (2.5 Gy / fraction)	66.6 Gy (1.8 Gy / fraction)	N/A
Five-Year Biochemical Failure	21%	18%	p = 0.3 (Similar)
Overall Grade 3 Adverse Events	16%	7%	p = 0.02 (Higher in HYPORT)
Grade 3 Renal and Urinary Disorders	13%	3%	p = 0.003 (Higher in HYPORT)

Balancing Efficacy Against Physician-Reported Toxicity

While patient-reported quality of life and bowel symptoms showed no statistically significant divergence at five years, the trial revealed a stark contrast in physician-documented adverse events. At the five-year evaluation, overall grade 3 adverse events reached 16 percent in the HYPORT group compared to 7 percent in the COPORT group. This discrepancy was primarily driven by grade 3 renal and urinary disorders, specifically noninfective cystitis and hematuria.

Lead author Mark Buyyounouski, MD, MS, FASTRO, at Stanford University highlighted the complex nature of evaluating post-treatment toxicity. Physician-reported measures capture clinical events and required medical interventions, whereas patient-reported outcomes reflect day-to-day functional symptoms and overall lifestyle impact. These divergent metrics offer complementary insights into how patients experience radiation therapy over time.

Funding and Research Support

This prospective clinical trial was supported by grants UG1CA189867 (NCORP), U10CA180822 (NRG Oncology SDMC), U10CA180868 (NRG Oncology Operations), and U24CA180803 (IROC) provided by the National Cancer Institute, a division of the National Institutes of Health. The findings reflect the consensus presented during the Clinical Trials Session of the American Society for Radiation Oncology Annual Meeting.

References

• American Society for Radiation Oncology (ASTRO). Clinical Trials Session: NRG-GU003 Trial Results. Boston, Massachusetts.
• National Cancer Institute (NCI). Grant Support Frameworks UG1CA189867, U10CA180822, U10CA180868, and U24CA180803.