SBRT Reduces Bowel Toxicity vs IMRT in Intermediate-Risk Prostate Cancer

Stereotactic body radiation therapy (SBRT) reduced rectal toxicity when compared with moderately hypofractionated intensity-modulated radiation therapy (IMRT) in patients with intermediate-risk prostate cancer, according to results from the phase 3 NRG-GU005 trial (NCT03367702) presented at the 2025 American Society for Radiation Oncology Annual Meeting.

The 5-year disease-free survival (DFS) rate was 89% (95% CI, 85%-92%) with SBRT compared with 92% (95% CI, 89%-95%) with moderately hypofractionated IMRT; the futility bound for DFS with 30% of SBRT over IMRT was crossed. The 3-year biochemical failure rate was 8% (95% CI, 5.2%-11.0%) compared with 4% (95% CI, 2.3%-7.0%), respectively, demonstrating a clinically significant increase with SBRT (P = .037). The 5-year overall survival (OS) rate was 91% (95% CI, 85%-95%) with SBRT compared with 94% (95% CI, 90%-97%) with IMRT (P = .66).

Concerning health-related quality of life, particularly bowel outcomes, the rate of minimal clinically important difference (MCID) was 35% with SBRT compared with 44% with IMRT, demonstrating a significant difference (P = .034). Per the longitudinal treatment effect, the least square mean difference was +2.68 (95% CI, 1.02-4.34), demonstrating significance (P = .0016).

Overall urinary toxicity was not significantly improved with SBRT vs moderately hypofractionated IMRT.

MCID was experienced by significantly fewer patients who received SBRT compared with patients who received IMRT in sexual and bowel health-related quality of life at 1 year, and urinary incontinence 2 years after treatment. The longitudinal analysis revealed that SBRT was superior to moderately hypofractionated IMRT for patient-reported urinary incontinence-related quality of life.

According to the investigators, SBRT was safe for the treatment of intermediate-risk prostate cancer.

“NRG GU-005 met a primary end point to decrease rectal toxicity vs [moderately hypofractionated] IMRT,” said presenting study author Rodney J. Ellis, MD, professor of Radiation Oncology and director of Clinical Research, Radiation Oncology, at University of Southern Florida Health and Tampa General Hospital, and coauthors, in the presentation. “[This is the] 1st phase 3 trial to report that the use of Rectal Spacer showed significant benefit for use on both [moderately hypofractionated] IMRT as well as SBRT.”

Between November 2017 and June 2022, a total of 698 patients with intermediate-risk prostate cancer were accrued for NRG-GU005 and randomly assigned to either the IMRT arm or the SBRT arm. In the IMRT arm, patients received 70 Gy in 28 fractions of 2.5 Gy to the prostate, or 60 Gy in 20 fractions of 3 Gy +/- proximal 1 cm of seminal vesicles; the minimal margins were 8 mm uniform in expansion, and 5 mm posteriorly. In the SBRT arm, patients received 36.25 Gy in 5 fractions of 7.25 Gy to the prostate +/- proximal 1 cm of seminal vesicles; the minimal margins were 5 mm superior, inferior, and laterally, and 3 mm anteriorly and posteriorly.

Patients were stratified by risk groups, use of rectal manipulation, and standard arm IMRT. The risk groups were those with a Gleason score of 7 (3+4) with a prostate-specific antigen (PSA) less than 10 ng/mL, those with a Gleason score of 7 (3+4) with a PSA greater than or equal to 10 ng/mL and less than 20 ng/ML, and those with a Gleason score of 6 (3+3) with a PSA greater than 10 ng/mL and less than 20 ng/mL. Rectal manipulation stratification included no use, use of rectal balloon, use of SpaceOAR hydrogel, and use of both SpaceOAR hydrogel and rectal balloon. IMRT standard arm stratification included 70 Gy in 28 fractions and 60 Gy in 20 fractions.

The primary end points of the trial were to determine whether SBRT was superior to hypofractionated IMRT regarding gastrointestinal and genitourinary toxicity via EPIC-26 bowel and urinary irritation domains, respectively, at 24. months post completion of therapy by MCID in EPIC-26, and whether SBRT was superior to hypofractionated IMRT for DFS.

“Further improvement may be feasible through microboost to the intraprostatic target to improve DFS while preserving QOL,” concluded the study authors.

Reference

Ellis RJ, Pugh S, Yu JB, et al. Primary results from NRG-GU005: A phase III trial of SBRT vs. hypofractionated IMRT for localized intermediate risk prostate cancer. Presented at the 2025 American Society for Radiation Oncology Annual Meeting; September 27-October 1, 2025; San Francisco, CA. Abstract 1.