Postmastectomy radiotherapy in intermediate-risk patients: the gray zone

Postmastectomy radiotherapy continues to be one of the most controversial issues in breast radiotherapy. At the crux of the controversy lies the lack of conclusive studies that specifically address the risk-benefit ratio of postmastectomy radiotherapy for patients at intermediate risk of developing locoregional recurrence. A well-designed phase III trial was initiated, but the trial failed to accrue and was closed prematurely, leaving the issue unresolved. Recent data confirm that postmastectomy radiotherapy yields a clear benefit in breast cancer-specific survival. Furthermore, the risk of cardiac morbidity that historically has offset the benefit of postmastectomy radiotherapy appears to be lessening with modern radiotherapy approaches. However, newer, more efficacious systemic therapy regimens may decrease the risk of locoregional recurrence and increase the risk of toxicity from combined-modality therapy. Recent studies attempt to better stratify patients into risk categories based on disease factors and to estimate the benefit of postmastectomy radiotherapy when traditional risk estimates, such as nodal status, are obscured by neoadjuvant systemic therapy. Nonetheless, a clear consensus on the role of postmastectomy radiotherapy remains elusive for patients who are at intermediate risk of locoregional recurrence after mastectomy.