Stereotactic Body Radiotherapy vs Moderately Hypofractionated IMRT for Localized Intermediate-Risk Prostate Cancer: A Randomized Clinical Trial. JAMA 2026 Sep 22;336(12):1029-1038
Date
08/13/2026Pubmed ID
42593775Pubmed Central ID
PMC13474103DOI
10.1001/jama.2026.12627Scopus ID
2-s2.0-105051224668 (requires institutional sign-in at Scopus site)Abstract
IMPORTANCE: The treatment of prostate cancer with radiotherapy is evolving. How quickly radiotherapy can be delivered, and the relative risks and benefits of such a treatment, is of significant public interest.
OBJECTIVE: To determine whether stereotactic body radiotherapy (SBRT) was superior to moderately hypofractionated intensity-modulated radiation therapy (MH-IMRT) in terms of patient-reported urinary irritative/obstructive and bowel quality of life and disease-free survival (DFS).
DESIGN, SETTING, AND PARTICIPANTS: NRG-GU005 was a phase-3, international, open-label, randomized clinical trial. The study was activated on November 16, 2017, and closed to accrual on June 8, 2022. Date of last follow-up was October 13, 2024. There were 136 centers in Asia, Canada, Europe, and the United States that accrued patients to the study. Patients with localized prostate cancer, clinical stage T1-T2b with Gleason 3 + 4 (grade group 2) and prostate-specific antigen (PSA) level less than 20 ng/mL or Gleason 3 + 3 (grade group 1) and PSA level 10 to 20 ng/mL were eligible. Intended accrual of 692 patients provided reductions of 8% and 10% in minimal clinically important decline (MCID) frequency for urinary-irritative/obstructive and bowel domains of the Expanded Prostate Cancer Index Composite-26 Item (EPIC-26) instrument at 2 years and greater than 80% power to detect a hazard ratio of 0.62 in DFS.
INTERVENTIONS: Patients were randomized 1:1 to receive SBRT (36.25 Gy in 5 fractions; n = 353) or MH-IMRT (70 Gy in 28 fractions or 60 Gy in 20 fractions; n =345).
MAIN OUTCOMES AND MEASURES: Primary outcomes were the frequency of an MCID in the urinary irritative/obstructive and bowel domains of the EPIC-26 at 2 years and DFS at 3 years.
RESULTS: A total of 698 patients were randomized. Median age was 68 years; 3% were Asian, 13% Black, and 80% White. Median follow-up was 3.2 years (range, 0-6.5). At 2 years, there was no significant difference in the urinary-irritative domain (35.4% vs 33.7%, P = .68). Urinary incontinence at 1 and 2 years after treatment and sexual function at 1 year after treatment favored SBRT. Fewer grade 3 + 4 genitourinary adverse events occurred in the SBRT vs MH-IMRT group (0.6% vs 2.5%, P = .04). There were significantly fewer MCIDs with SBRT vs MH-IMRT in the bowel domain (34.9% vs 43.8%, P = .03). At 3 years, DFS for MH-IMRT was 92.1% (95% CI, 88.9%-95.2%) vs 88.6% for SBRT (95% CI, 85.2%-92.1%) (1-sided log-rank P < .001).
CONCLUSIONS AND RELEVANCE: Stereotactic body radiotherapy using a modest dose prescription improved multiple quality-of-life domains but was not superior to MH-IMRT in terms of DFS. The rate of PSA failure was not significantly improved in the SBRT vs MH-IMRT group.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03367702.
Author List
Ellis RJ, Pugh SL, Yu JB, Feng FY, Konski AA, Grubb RL 3rd, Wallace RE, Gladstone DJ, Ménard C, Miccio JA, Frazier AJ, Pennington JD, Michalski JM, Spratt DE, Martinez A, Morgan SC, Mihai A, Solanki AA, Amjad A, Straza MW, Delouya G, Schroeder TM, Marshall DT, Kapadia N, Patel AN, Cescon TP, El-Gayed A, Yoon HA, Paulus R, Sandler HM, NRG-GU005 Collaborative AuthorsAuthor
Michael W. Straza MD, PhD Associate Professor in the Radiation Oncology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAged
Aged, 80 and over
Defecation
Disease-Free Survival
Follow-Up Studies
Humans
Male
Middle Aged
Neoplasm Grading
Neoplasm Staging
Prostate-Specific Antigen
Prostatic Neoplasms
Quality of Life
Radiosurgery
Radiotherapy, Intensity-Modulated
Urinary Incontinence
Urinary Tract
Urination
