Stereotactic Body Radiotherapy vs Moderately Hypofractionated IMRT for Localized Intermediate-Risk Prostate Cancer: A Randomized Clinical Trial
Five-treatment radiation improved bowel quality but not cancer control.
*Open-label randomized clinical trial; Level 2 (OCEBM 2011).
Citation
Ellis RJ, Pugh SL, Yu JB, et al. JAMA. Published August 13, 2026. doi:10.1001/jama.2026.12627
Background
Shorter radiation schedules may reduce treatment burden for men with localized prostate cancer. This trial tested whether 5 treatments improved quality of life and cancer outcomes.
Patients
698 men with untreated localized intermediate-risk prostate cancer. Important exclusions included prostate volume at least 70 mL, stage T3 disease on magnetic resonance imaging, prostate-specific antigen at least 20 ng/mL, or higher-risk disease.
Intervention
Stereotactic body radiation: 36.25 Gray units in 5 treatments.
Control
Moderately shortened intensity-modulated radiation: 70 Gray units in 28 treatments or 60 in 20.
Outcome
Primary outcomes were patient-reported bowel and urinary symptom decline at 2 years using the Expanded Prostate Cancer Index–26 (0-100; higher is better), and disease-free survival at 3 years.
Follow-up Period
Median 3.2 years.
Results
| Outcome | Stereotactic vs control | Effect |
|---|---|---|
| Bowel decline, 2 years (primary) | 34.9% vs 43.8% | Absolute reduction 8.9% (95% CI 0.7 to 17.0); patients needed to treat 12 (CI not reported) |
| Other quality declines favoring stereotactic treatment | Bowel 1 year, urinary leakage 2 years, sexual function 1 year | Absolute reductions 12.8% (95% CI 4.6 to 20.9), 8.9% (95% CI 1.2 to 16.6), and 9.5% (95% CI 1.2 to 17.9) |
| Prostate-specific antigen failure | Higher with stereotactic treatment | HR 1.82 (95% CI 1.01 to 3.27) |
| Severe urinary/genital adverse events | 0.6% vs 2.5% | Absolute reduction 1.9% (CI not reported); patients needed to treat 53 (CI not reported) |
Disease-free survival at 3 years was 88.6% (95% CI 85.2 to 92.1) with stereotactic treatment versus 92.1% (95% CI 88.9 to 95.2) with control; stereotactic treatment was not superior.
Results used intention-to-treat analysis. The control was an available current treatment. Prespecified minimally important declines were used. Prostate-specific antigen failure appeared to drive cancer-control concern.
Limitations
Open-label design, no noninferiority testing, limited quality-of-life follow-up beyond 2 years, and possible false prostate-specific antigen rises after stereotactic treatment. Findings apply to selected intermediate-risk patients, not higher-risk or large-prostate populations.
Funding
National Cancer Institute; author industry relationships may introduce bias concerns.
Clinical Application
Discuss 5-treatment radiation for convenience and bowel outcomes, but do not prefer it over current moderate-course radiation for cancer control.
Discussion
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In this open-label phase 3 RCT, SBRT reduced bowel MCID declines (34.9% vs 43.8%) but had lower 3-year DFS than MH-IMRT (88.6% vs 92.1%; HR 1.38). How should we weigh validity, patient priorities, and applicability before offering SBRT routinely? This trial was designed to test whether SBRT was superior to MH-IMRT for disease-free survival. Given that 3-year DFS was 88.6% with SBRT vs 92.1% with MH-IMRT, which interpretation is most appropriate?