SBRT improves bowel health related quality-of-life in patients with localized intermediate-risk prostate cancer

Results of the NRG Oncology NRG-GU005 clinical study comparing stereotactic body radiation therapy (SBRT) to moderately hypofractionated intensity-modulated radiation therapy (MH-IMRT) for patients with localized intermediate risk prostate cancer indicate that the use of SBRT improved bowel health related quality of life (HRQOL) in this patient population. There was no significant improvement for SBRT seen for the other primary objectives including urinary HRQOL and disease-free survival. These results are now published in the Journal of the American Medical Association (JAMA) following the presentation during the Plenary Session of the 2025 American Society for Radiation Oncology Annual Meeting in San Francisco, California.

Although the NRG-GU005 trial was not positive, the HRQOL endpoint showed that SBRT was associated with a positive outcome in the EPIC-26 bowel domain quality-of-life measure but not the urinary irritative/obstructive domain. The secondary genitourinary endpoints showed that SBRT had lower incontinence related quality of life and improved maintenance of erectile dysfunction versus moderately hypo fractionated IMRT . The Disease-Free Survival (DFS) co-primary endpoint was reported early because of futility of superiority related solely to higher biochemical failure, determined by PSA, in the SBRT arm. Further follow-up is warranted to assess the longer-term results. PACE-B showed SBRT is non-inferior to IMRT, and now NRG-GU005 shows SBRT is less likely to adversely affect aspects of patients' quality of life as determined by these patient-reported outcomes." 

Rodney J. Ellis, MD, University of South Florida and lead author of the NRG-GU005 abstract

The Phase III NRG-GU005 trial enrolled 698 evaluable patients with intermediate-risk prostate cancer. Trial participants were randomly assigned to either receive SBRT at 36.25 Gy in 5 fractions or IMRT at 70 Gy in 28 fractions or 60 Gy in 20 fractions. The trial had co-primary endpoints of DFS and HRQOL, the latter measured using the bowel and urinary irritative or obstructive domains of the EPIC-26. Both co-endpoints needed to be met for the trial to be positive. Fewer patients on the SBRT arm experienced a minimally clinically important difference (MCID in bowel HRQOL at 2 years than patients receiving IMRT (34.9% vs. 43.8%, p=0.034). Longitudinal models showed SBRT and use of rectal spacers led to improved bowel domain scores. However, there was no significant difference in MCID frequency for the urinary irritative or obstructive symptoms domain between patients receiving SBRT or IMRT (33.7% vs. 34.7%, p=0.68). Thus, the HRQOL co-primary endpoint was not met. Additionally, the interim analysis of this study crossed the futility boundary for DFS, thus indicating SBRT is not superior over hypofractionated IMRT in this patient population.

"This major clinical trial teaches us not only about state-of-the-art radiation technology, but also about the biology of radiation effects on prostate cancer and normal organs responsible for basic human functions," said Dr. Mitchell Machtay from Penn State and the NRG Group Deputy Chair and Chief Scientific Officer, "It will influence radiation oncology practice and future research for years to come. We owe a great deal of gratitude to the patients who participated in this study."

This project was supported by grants UG1CA189867 (NCORP), U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), U24CA180803 (IROC), from the National Cancer Institute (NCI), part of National Institutes of Health. NRG GU005 is led by NRG Oncology and conducted by the NCI funded National Clinical Trials Network (NCTN).