Top Line: Radiation must continuously prove its worth across disease sites with ever-improving systemic therapies.
The Study: Today we bring you the long-awaited results of the phase 3 SUPREMO trial. This was an international, but mostly UK, trial that prospectively randomized 1679 women between 2006 and 2013 following mastectomy for “intermediate-risk” breast cancer to +/- “chestwall” radiation. Intermediate risk was defined as pT1-2N1 (72%) or pT3N0 (0.5%) or pT2N0 combined with grade 3 and/or the presence of lymphovascular invasion (23%). The hope was this trial would modernize outcomes reporting in a cohort receiving modern systemic therapy, namely anthracyclines +/- taxanes and HER2-targeted therapies. Importantly, while sentinel node sampling could be performed initially, all those with pN1 disease proceeded to axillary clearance of at least 8 nodes. The median number of nodes removed across all enrollees was 14. More importantly–head-scratching even?–is detailing of radiation volumes. The chest wall was the only explicit target. Axillary volumes were not allowed, and supraclavicular (12% of radiation arm) and internal mammary (1.5%) volumes were only included at physician discretion. The primary endpoint of overall survival at ten years with or without radiation was virtually identical at roughly 82%, as was disease-free survival at 76% and distant disease-free survival at 78-79%. The only significant difference squeaked out was chest wall recurrence which occurred in 1.1% with radiation and 2.5% without. For historical context, the power calculation performed in 2006 was based on an estimated overall survival at 10 years of 56% and chest wall recurrence up to 15% without irradiation. So just a little off. Ultimately, the elephant in the room is recognized by the authors, who make an interesting 180: “We recognize the recent shift from axillary node clearance to regional nodal irradiation as primary treatment. If regional nodal irradiation is warranted, modern radiotherapy techniques can deliver a homogeneous dose to the lymph-node target volumes while avoiding the chest wall or reconstructed breast.”
TBL: For patients with intermediate risk breast cancer, radiation to the chest wall (mostly without RNI) after mastectomy did not improve treatment outcomes. | Kunkler, N Engl J Med 2025
The Study: Today we bring you the long-awaited results of the phase 3 SUPREMO trial. This was an international, but mostly UK, trial that prospectively randomized 1679 women between 2006 and 2013 following mastectomy for “intermediate-risk” breast cancer to +/- “chestwall” radiation. Intermediate risk was defined as pT1-2N1 (72%) or pT3N0 (0.5%) or pT2N0 combined with grade 3 and/or the presence of lymphovascular invasion (23%). The hope was this trial would modernize outcomes reporting in a cohort receiving modern systemic therapy, namely anthracyclines +/- taxanes and HER2-targeted therapies. Importantly, while sentinel node sampling could be performed initially, all those with pN1 disease proceeded to axillary clearance of at least 8 nodes. The median number of nodes removed across all enrollees was 14. More importantly–head-scratching even?–is detailing of radiation volumes. The chest wall was the only explicit target. Axillary volumes were not allowed, and supraclavicular (12% of radiation arm) and internal mammary (1.5%) volumes were only included at physician discretion. The primary endpoint of overall survival at ten years with or without radiation was virtually identical at roughly 82%, as was disease-free survival at 76% and distant disease-free survival at 78-79%. The only significant difference squeaked out was chest wall recurrence which occurred in 1.1% with radiation and 2.5% without. For historical context, the power calculation performed in 2006 was based on an estimated overall survival at 10 years of 56% and chest wall recurrence up to 15% without irradiation. So just a little off. Ultimately, the elephant in the room is recognized by the authors, who make an interesting 180: “We recognize the recent shift from axillary node clearance to regional nodal irradiation as primary treatment. If regional nodal irradiation is warranted, modern radiotherapy techniques can deliver a homogeneous dose to the lymph-node target volumes while avoiding the chest wall or reconstructed breast.”
TBL: For patients with intermediate risk breast cancer, radiation to the chest wall (mostly without RNI) after mastectomy did not improve treatment outcomes. | Kunkler, N Engl J Med 2025