Stereotactic Body Radiotherapy vs Moderately Hypofractionated IMRT for Localized Intermediate-Risk Prostate Cancer: A Randomized Clinical Trial.

Abstract

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. 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). 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. 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). 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. 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). 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. ClinicalTrials.gov Identifier: NCT03367702.