New joint clinical practice guidelines from ASTRO, ASCO, and SSO, published in the Journal of Clinical Oncology, provide the most comprehensive update in a decade on postmastectomy radiation therapy (PMRT) for breast cancer. The guidelines re-examine indications for PMRT after upfront surgery, evaluate its role following neoadjuvant systemic therapy (NAST), and refine recommendations on target volumes, dose-fractionation, and modern delivery techniques. For practicing radiation oncologists, these recommendations sharpen the clinical decision-making framework while reflecting the evolving landscape of systemic therapy and imaging.
The guidelines reaffirm that PMRT remains strongly recommended for most patients with node-positive disease following upfront mastectomy. At the same time, they clarify that patients with node-negative disease generally do not require PMRT unless they present with specific high-risk features such as large tumors (pT3 or pT4), lymphovascular invasion, or aggressive biologic subtypes. This nuanced approach allows physicians to weigh locoregional control against the potential toxicity of treatment and better individualize care. In the neoadjuvant setting, PMRT is advised for patients with locally advanced disease (cT4 or cN2-3) or those with residual nodal involvement (ypN+) after NAST, regardless of the degree of response. However, for patients who initially present with cT1-3N1 or cT3N0 disease and convert to pathologically node-negative status after systemic therapy, the recommendation is conditional and should hinge on individual risk factors such as young age, lymphovascular invasion, or tumor biology. This conditional guidance reflects the growing recognition that pathologic complete response confers a lower risk of recurrence, while also acknowledging that certain subsets remain at appreciable risk.
For clinicians, these recommendations underscore a shift toward risk-stratified PMRT, reflecting both advances in systemic therapy and the growing precision of modern radiation delivery. As systemic regimens achieve higher rates of pathologic complete response, physicians can increasingly avoid overtreatment of low-risk patients while still offering aggressive therapy to those with residual disease. Dr. Youssef H. Zeidan, radiation oncologist at the Eugene M. & Christine E. Lynn Cancer Institute at Boca Raton Regional Hospital, part of Baptist Health, who co-authored the new guidelines, observes that “the updated guidelines allow us to more precisely balance toxicity and benefit, particularly in patients who achieve good response with neoadjuvant therapy. We can confidently reduce overtreatment in ypN0 patients who have favorable features.” His perspective captures the central goal of the new guidelines: aligning evidence with individualized risk to optimize the therapeutic ratio.
At the same time, the guidelines highlight the continuing importance of meticulous technique. Dr. Zeidan emphasizes, “In patients with node-positive disease, the guidelines reinforce that PMRT remains essential for improving locoregional control and survival, but our technique must be optimized using CT planning, IMRT or 3Dconformal approaches, and cardiac sparing measures – to minimize harm.” This attention to detail reflects the reality that clinical benefit depends not only on deciding who should receive PMRT, but also on how precisely and safely the radiation is delivered.
Dr Zeidan adds, “These guidelines are made possible by the tenacious efforts of our scientific and patient communities through adopting rigorous clinical research. Our utilization of PMRT will continue to evolve as randomized clinical trials on the topic report their findings.” Meanwhile, multidisciplinary discussions and shared decision making are key for choosing the optimal treatment paradigm for each patient. Institutions are encouraged to review their fractionation protocols, consider broader adoption of moderate hypofractionation, and ensure consistent CT-based planning and image guidance across all cases.
Overall, the 2025 ASTRO-ASCO-SSO guidelines represent a significant step forward in tailoring PMRT to the individual patient. By refining criteria for treatment after both upfront surgery and neoadjuvant therapy, clarifying target volumes, and endorsing modern hypofractionated techniques with heart- and lung-sparing strategies, they provide physicians with a clear and practical framework to improve patient outcomes while reducing unnecessary toxicity. As Dr. Zeidan underscores, the updated recommendations give clinicians the tools “to confidently reduce overtreatment in patients who have favorable features,” while ensuring that “PMRT remains essential for improving locoregional control and survival in higher-risk cases.” The message is clear – personalized decision-making, multidisciplinary collaboration, and meticulous execution are the hallmarks of contemporary postmastectomy radiation therapy.
