Reconsidering the role of PMRT in low to intermediate risk breast cancer: Applying results from previous standards of treatment in the current multimodal practice

The recently published 10-year results of the SUPREMO trial offer valuable insights into the role of postmastectomy radiotherapy (PMRT) to the chest wall alone in low- to intermediate-risk breast cancer patients. However, the trial s design and evolving standards in surgery, radiation therapy (RT), and systemic therapy necessitate careful interpretation. Main findings. SUPREMO enrolled 1,600 patients, primarily with pT1-2N1M0 and pT3N0M0 disease, and reported no significant overall survival (OS) benefit at 10 years. Major protocol modifications-including reduced sample size, extended accrual, and broadened eligibility criteria-were required to ensure trial completion but compromised statistical power and generalizability. The trial s limited use of regional nodal irradiation (RNI), including internal mammary node (IMN) coverage, further limits its applicability in the context of modern evidence demonstrating clear survival benefits from comprehensive RNI. Moreover, pathology quality assurance discrepancies, evolving surgical practices (from modified radical mastectomy to more conservative approaches), and advances in systemic therapy have fundamentally altered risk profiles and treatment paradigms. CONCLUSION: While SUPREMO contributes to understanding PMRT's historical role, its relevance to contemporary multimodal breast cancer management is limited. The restriction to chest wall irradiation, omission of RNI, and the predominance oflower-end intermediate-risk disease(including many patients withnode-negative or limited nodal involvement) diminish its clinical impact. Future trials must integrate biology-driven risk stratification, contemporary surgical and systemic standards, and precise RT definitions, requiring pragmatic designs, robust QA, and accelerated accrual to remain relevant and avoid undertreatment in selected patients who may still benefit from PMRT.