The Absolute Effect / Evidence / Breast Cancer
SUPREMO
Clinical question: After mastectomy and contemporary systemic therapy for intermediate-risk breast cancer, does chest-wall irradiation improve overall survival or reduce recurrence?
Registry: ISRCTN61145589 · One underlying study; aliases and follow-up publications consolidated.
Design, population and eligibility
International, phase III randomized trial evaluating chest-wall irradiation versus no chest-wall irradiation after mastectomy and systemic therapy.
1,607 patients in the intention-to-treat population: 808 assigned chest-wall irradiation and 799 no irradiation.
Intermediate-risk disease defined as pT1N1, pT2N1, pT3N0, or pT2N0 with grade 3 and/or lymphovascular invasion after mastectomy, axillary procedure and systemic therapy.
Median follow-up 9.6 years; primary OS analysis at 10 years.
Treatment and comparator
Intervention: Chest-wall irradiation, 40–50 Gy, after mastectomy and axillary surgery. Comparator: No chest-wall irradiation. The trial isolated chest-wall irradiation; it should not be conflated with a trial of comprehensive regional nodal irradiation.
Primary and secondary endpoints
Primary endpoint: overall survival at 10 years. Secondary endpoints included chest-wall recurrence, regional recurrence, DFS, distant metastasis-free survival and radiation-related adverse events.
Key efficacy results
Ten-year OS was 81.4% with chest-wall irradiation versus 81.9% without; HR 1.04 (95% CI 0.82–1.30; p=0.80). Ten-year DFS was 76.2% versus 75.5%; HR 0.97 (95% CI 0.79–1.18). Distant metastasis-free survival was 78.2% versus 79.2%; HR 1.06 (95% CI 0.86–1.31).
Chest-wall recurrence occurred in 9/808 (1.1%) versus 20/799 (2.5%); HR 0.45 (95% CI 0.20–0.99). The absolute difference was less than 2 percentage points.
Source-reported outcome visualization
Ten-year overall survival, the prespecified primary endpoint.
The primary endpoint was OS. Chest-wall recurrence is reported separately in the text and is not plotted on the OS scale.
Absolute effect
No OS benefit was demonstrated. The observed chest-wall recurrence difference was 1.4 percentage points (1.1% versus 2.5%). Approximate NNT 72 at 10 years to prevent one chest-wall recurrence, calculated from the observed proportions; this is not an NNT for survival and the absolute reduction was small.
Trial-specific toxicity and treatment burden
Radiation-related adverse events were assessed; the primary abstract does not provide a single comparative grade 3–5 toxicity rate suitable for an NNH. Chest-wall irradiation adds treatment visits, acute skin reaction, fatigue and potential late chest-wall, pulmonary, cardiac and reconstruction-related effects. The exact risk depends on technique, laterality and individual anatomy.
Quality of life and patient-reported outcomes
No clinically meaningful global QoL advantage was established in the primary survival report. The balance is a small reduction in chest-wall recurrence against treatment burden and potential late effects.
Subgroups and applicability
The trial population was defined by intermediate-risk pathological groups. These results should not be extrapolated to patients with greater nodal burden or other high-risk features. The regional nodal irradiation question is distinct.
Current-practice context · reviewed 2 November 2026
SUPREMO supports individualized omission of chest-wall irradiation in the specific intermediate-risk population studied when modern systemic therapy and surgery have been delivered. It does not overturn PMRT indications for higher-risk node-positive disease, nor does it answer the benefit of regional nodal irradiation.
Limitations and critical interpretation
The primary endpoint was OS; event rates were low and confidence intervals exclude neither modest benefit nor harm. The observed chest-wall recurrence difference was small. The study tested chest-wall irradiation, not comprehensive PMRT in all high-risk groups.
Bottom line: SUPREMO found no 10-year OS or DFS improvement from chest-wall irradiation in its intermediate-risk cohort, although chest-wall recurrence was reduced from 2.5% to 1.1%. Use the result to refine, not abolish, PMRT indications.
Primary sources and follow-up publications
All outcome values above are transcribed from the linked trial reports or their prespecified follow-up publications. Unreported values are not imputed. No NNT is derived from median survival.