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

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 (QOL) and disease-free survival (DFS). Design, Setting, Participants NRG-GU005 was a phase-3, international, open-label, randomized, controlled trial. The study was activated 11/16/2017 and closed to accrual on 6/8/2022. Date of last follow up was 10/13/2024. There were 121 centers in the United States, 13 in Canada, and 2 in Asia that accrued patients to the study. Patients with localized prostate cancer, clinical stage T1-T2b with Gleason 3+4 (Grade group 2) and PSA < 20 ng/mL or Gleason 3+3 (Grade group 1) and PSA 10–20 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) at 2 years and >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) or MH-IMRT (70 Gy in 28 fractions or 60 Gy in 20 fractions). Main Outcomes and Measures Primary outcomes were the frequency of a MCID in the urinary irritative/obstructive and bowel domains of the EPIC-26 at 2 years and DFS at 3 years. Results NRG-GU005 randomized 698 patients. Median follow-up was 3.2 years (min-max: 0–6.5). At 2 years, there were no significant difference in the urinary-irritative domain (35.4% vs. 33.7%, p=0.68). Urinary incontinence at 1- and 2-years post-treatment and sexual function at 1-year post-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 MCID with SBRT vs. MH-IMRT in the bowel domain (34.9% vs. 43.8%, p=0.034) At 3 years, DFS for MH-IMRT was 92.1% (95% confidence interval [CI]: 88.9–95.2) vs. 88.6% for SBRT (95% CI: 85.2–92.1) (one-sided log-rank p<0.0001). Conclusions and Relevance SBRT utilizing a modest dose prescription improved multiple QOL domains, but was not superior to MH-IMRT in terms of DFS and. The rate of PSA failure was not significantly improved in the SBRT vs. MH-IMRT arm. Trial Registration: Clinicaltrials.gov identifier: NCT03367702