Philadelphia—A large randomized clinical trial has found that stereotactic body radiation therapy (SBRT), an increasingly used form of highly focused prostate cancer treatment, may reduce certain bowel-related quality-of-life problems compared with moderately hypofractionated intensity-modulated radiation therapy (MH-IMRT). The result comes from the phase III NRG-GU005 trial, which compared the two radiation strategies in men with localized intermediate-risk prostate cancer. Although patients receiving SBRT reported better bowel health at two years, the study did not demonstrate a significant advantage for urinary quality of life, and it failed to show that SBRT improved disease-free survival. The findings, published in the Journal of the American Medical Association after presentation at the 2025 annual meeting of the American Society for Radiation Oncology, offer a detailed look at how shorter radiation schedules affect both tumor control and the everyday functioning of patients.
Prostate cancer is particularly suited to precision radiation because the prostate is a relatively small organ that can be targeted from multiple directions while attempting to limit exposure to surrounding tissues. SBRT delivers a high biological dose in a small number of treatment sessions, using advanced image guidance and treatment planning to account for organ motion and anatomy. In NRG-GU005, patients assigned to the SBRT group received 36.25 Gy in five fractions. Patients in the comparison group received MH-IMRT, delivered either as 70 Gy in 28 fractions or 60 Gy in 20 fractions. While conventional radiation may require several weeks of daily visits, SBRT can be completed in approximately one week, a difference that could reduce travel, treatment costs, time away from work, and the logistical burden on patients and families.
The trial enrolled 698 evaluable participants with intermediate-risk disease and was designed around two co-primary endpoints: disease-free survival and patient-reported health-related quality of life. Researchers assessed quality of life with the 26-item Expanded Prostate Cancer Index Composite, commonly known as EPIC-26. The instrument measures treatment effects in several domains, including bowel function, urinary irritative and obstructive symptoms, urinary incontinence, sexual function, and hormonal symptoms. For the primary quality-of-life analysis, investigators focused on whether patients experienced a minimally clinically important difference, or MCID, in bowel health or urinary irritative and obstructive symptoms. An MCID is intended to represent a change noticeable and meaningful to patients rather than merely a statistically measurable difference in a score.
At two years, 34.9 percent of men treated with SBRT experienced an MCID in the bowel domain, compared with 43.8 percent of those treated with MH-IMRT. The difference was statistically significant, with a p value of 0.034, indicating that the probability of observing such a result by chance alone was relatively low under the study’s statistical assumptions. Longitudinal analyses, which examine changes over time rather than relying on a single follow-up point, also associated SBRT with improved bowel-domain scores. The use of rectal spacers was linked to better bowel outcomes as well. These devices are placed between the prostate and rectum to increase physical separation, potentially reducing the amount of radiation delivered to the rectal wall during treatment.
The bowel result did not extend to the trial’s urinary co-primary endpoint. An MCID in urinary irritative or obstructive symptoms occurred in 33.7 percent of patients in the SBRT arm and 34.7 percent in the MH-IMRT arm. The difference was not statistically significant, with a p value of 0.68. Urinary irritation and obstruction can result from radiation-related inflammation or changes in the prostate and urethra, and the similar rates in both groups suggest that delivering radiation in five fractions did not substantially alter this aspect of recovery compared with moderately shortened IMRT. Because both quality-of-life domains had to meet the prespecified criteria for the co-primary endpoint to be considered positive, the urinary result meant that the trial did not fulfill its overall health-related quality-of-life objective.
The study also did not establish a disease-control advantage for SBRT. An interim analysis crossed the trial’s futility boundary for superiority, meaning that the accumulating data made it unlikely that SBRT would ultimately prove superior to MH-IMRT for disease-free survival. According to the investigators, this conclusion was driven solely by a higher number of biochemical failures in the SBRT group. Biochemical failure is generally identified through rising prostate-specific antigen, or PSA, after treatment. PSA is a sensitive marker of prostate activity, but a biochemical recurrence does not always immediately correspond to visible metastatic disease or a decline in overall survival. Longer follow-up remains important because prostate cancer can recur many years after initial treatment, and early PSA patterns may not fully predict long-term clinical outcomes.
The investigators reported additional differences in patient-reported genitourinary outcomes. SBRT was associated with lower incontinence-related quality of life, indicating a less favorable experience in that specific domain, while it was also associated with improved maintenance of erectile dysfunction compared with MH-IMRT. These findings illustrate why radiation comparisons cannot be reduced to a single measure of toxicity. A treatment may perform better for bowel symptoms while producing different trade-offs in urinary continence or sexual function. The prostate, rectum, bladder, urethra, and neurovascular structures occupy a tightly packed region of the pelvis, and radiation dose, fraction size, baseline function, anatomy, technical planning, and the use of protective devices can all influence late effects.
The NRG-GU005 results add to evidence from other randomized studies examining shorter prostate radiation schedules. The PACE-B trial previously showed that SBRT was non-inferior to conventionally fractionated or moderately hypofractionated radiation for disease control in an appropriate patient population. NRG-GU005 was designed to ask a more demanding question: whether SBRT could deliver superior disease-free survival while also producing a clinically meaningful improvement in selected quality-of-life outcomes. The answer was no under the trial’s predefined criteria. Nevertheless, the bowel findings may be relevant to shared decision-making, particularly for patients who value fewer treatment visits and are concerned about gastrointestinal effects. Physicians will still need to weigh these potential advantages against urinary and sexual side effects, baseline symptoms, prostate anatomy, rectal spacer availability, and the uncertainty surrounding long-term biochemical control.
“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,” Mitchell Machtay of Penn State, NRG Oncology’s group deputy chair and chief scientific officer, said in a statement. Rodney J. Ellis of the University of South Florida, the study’s lead author, said the trial was not positive overall but noted that SBRT produced a favorable outcome in the EPIC-26 bowel domain and not in the urinary irritative or obstructive domain. He emphasized that additional follow-up is needed to clarify longer-term outcomes. The trial was supported by the National Cancer Institute through the National Clinical Trials Network and conducted by NRG Oncology, a research group formed from the legacy Radiation Therapy Oncology Group, National Surgical Adjuvant Breast and Bowel Project, and Gynecologic Oncology Group programs. For now, the findings suggest that SBRT is a time-saving alternative with a distinct quality-of-life profile, not a universally superior replacement for MH-IMRT.
Subject of Research: SBRT versus moderately hypofractionated IMRT for localized intermediate-risk prostate cancer
Article Title: Stereotactic Body Radiotherapy vs Moderately Hypofractionated IMRT for Localized Intermediate-Risk Prostate Cancer: A Randomized Clinical Trial
News Publication Date: August 13, 2026
Web References: https://pubmed.ncbi.nlm.nih.gov/42593775/
References: Ellis RJ, Pugh SL, Yu JB, et al. “Stereotactic Body Radiotherapy vs Moderately Hypofractionated IMRT for Localized Intermediate-Risk Prostate Cancer: A Randomized Clinical Trial.” Journal of the American Medical Association. 2026. doi:10.1001/jama.2026.12627.
Keywords: prostate cancer, SBRT, stereotactic body radiation therapy, IMRT, hypofractionated radiotherapy, NRG-GU005, radiation oncology, quality of life, EPIC-26, disease-free survival, PSA, rectal spacers
