Postmastectomy Chest-Wall Irradiation in the Modern Systemic Therapy Era: Lessons from SUPREMO

Postmastectomy chest-wall irradiation (PM-CWI) has historically been recommended for node-positive breast cancer, based on Danish (1997) and Canadian (1999) trials and EBCTCG (2014) meta-analyses conducted before modern systemic therapies. With contemporary chemotherapy, endocrine therapy, anti-HER2 agents and immunotherapy substantially reducing recurrence risk, the benefit of routine PM-CWI in intermediate-risk patients has been questioned.

The value of postmastectomy chest-wall irradiation in patients with one to three positive axillary nodes or high-risk node-negative breast cancer remains unclear. Two recent NEJM publications address this uncertainty1,2. SUPREMO was a large international randomised trial of 1,679 women with intermediate-risk disease (pT1–2N1 or pT3N0 or pT2N0 with grade 3 histology and/or lymphovascular invasion), all treated with mastectomy, axillary surgery and systemic therapy, comparing PM-CWI versus no irradiation. The primary endpoint was 10-year overall survival.

After almost 10 years’ follow-up, overall survival was identical: 81.4% with PM-CWI versus 81.9% without. While PM-CWI reduced chest-wall recurrence (n=9, 1.1% vs n=20, 2.5%), the absolute benefit was small (1.4%), equating to a number-needed-to-treat of 71 to prevent one recurrence. Disease-free and distant recurrence-free survival were also unchanged. These findings demonstrate that, in the modern systemic therapy era, improved local control does not translate into a survival advantage for intermediate-risk patients. The study advocates for a re-evaluation of clinical guidelines to spare patients from potential radiation side effects when the survival benefits are equivalent.

An exploratory signal of worse survival with PM-CWI in triple-negative disease was observed, echoing findings from other contemporary trials, but requires further study.

Key Implications: In appropriately selected intermediate-risk patients receiving modern systemic therapy, PM-CWI can be safely omitted. SUPREMO supports personalised de-escalation of radiotherapy, with important benefits for reconstructive outcomes and reduced treatment morbidity, without compromising survival.

Note of caution: SUPREMO mandated axillary-node clearance for node-positive patients, a practice no longer standard given evidence supporting axillary de-escalation in selected cases. However, mastectomy patients were underrepresented in prior trials and radiotherapy was frequently used, meaning the safety of omitting both axillary clearance and postmastectomy radiotherapy remains unproven, requiring individualised multidisciplinary decision-making until further prospective data are available (e.g. T-REX Trial).

1. Kunkler IH, Russell NS, Anderson N, et al. Ten-Year Survival after Postmastectomy Chest-Wall Irradiation in Breast Cancer. N Engl J Med. 2025 Nov 6;393(18):1771-1783. doi: 10.1056/NEJMoa2412225. PMID: 41191939; PMCID: PMC7618363.
2. de Boniface J. Omission of Chest-Wall Irradiation after Mastectomy for Breast Cancer. N Engl J Med. 2025 Nov 6;393(18):1852-1853. doi: 10.1056/NEJMe2512077. PMID: 41191945.

Summary Author: Edward St John, Consultant Oncoplastic Breast Surgeon & Honorary Associate Professor. Portsmouth Hospitals University NHS Trust & University of Portsmouth.