Results from the phase 3 NRG-GU005 trial, presented at the 2025 American Society for Radiation Oncology Annual Meeting, show that stereotactic body radiation therapy (SBRT) significantly reduces rectal toxicity compared to moderately hypofractionated intensity-modulated radiation therapy (IMRT) for patients with intermediate-risk prostate cancer.
The shift toward SBRT—which delivers higher doses of radiation in far fewer sessions—aims to maintain cancer control while slashing the time patients spend in the clinic. New data suggests this approach doesn’t just save time; it may actively protect the bowel.
NRG-GU005 Trial: Rectal Toxicity and Quality of Life
The NRG-GU005 trial focused on 698 patients with intermediate-risk prostate cancer accrued between November 2017 and June 2022. Researchers compared SBRT, delivered in five fractions of 7.25 Gy, against moderately hypofractionated IMRT. The primary goal was to determine if SBRT could reduce gastrointestinal and genitourinary toxicity.
The results showed a clear advantage for SBRT regarding bowel health. The rate of minimal clinically important difference (MCID) in the bowel domain was 35% with SBRT compared with 44% with IMRT. This difference was statistically significant, with a longitudinal treatment effect favoring SBRT (p = 0.0016).
While the bowel outcomes were superior, the trial found that overall urinary toxicity did not see a significant improvement. However, secondary analysis indicated that SBRT favored patients in terms of urinary incontinence at two years and sexual health at one year.
Balancing Cancer Control and Treatment Convenience
The clinical trade-off in radiation therapy is often between the aggressiveness of the dose and the risk of recurrence. In the NRG-GU005 trial, the 5-year overall survival rate remained similar between the two groups: 91% for SBRT and 94% for IMRT. However, the 3-year biochemical failure rate was slightly higher for SBRT at 8%, compared to 4% for IMRT.
The convenience is stark. SBRT compresses the entire course into just five sessions.
The Role of Rectal Spacers and Precision Margins
The success of SBRT in reducing toxicity is not just about the dose, but the precision of the delivery.
A critical factor in protecting healthy tissue is the use of rectal spacers, such as SpaceOAR Hydrogel. These devices create physical distance between the prostate and the rectum to minimize radiation exposure to the bowel. Dr. Ellis highlighted that NRG-GU005 is the first phase 3 trial to report that rectal spacers showed significant benefit for both SBRT and moderately hypofractionated IMRT.
This technical precision allows for a higher dose per session without increasing the risk of long-term scarring.
Long-term Outcomes and Clinical Shift
While the NRG-GU005 trial provides recent phase 3 evidence, older cohort data supports the safety of the 5-fraction approach. A 7-year study of 515 patients treated with SBRT using Cyberknife technology found that late rectal toxicity was low at 4%, and 67% of patients who were potent at baseline remained so at the last follow-up.
The convergence of these findings suggests a shift in the standard of care. By reducing the number of clinic visits, healthcare systems can treat more patients in less time, while patients avoid the schedule of conventional radiation.
