Regional radiotherapy after primary systemic treatment for cN+ breast cancer patients

Pathologic complete response (pCR) after Primary Systemic Treatment (PST) for breast cancer is associated with excellent long-term outcomes. With increasing use of PST, the indication for regional nodal irradiation (RNI) has been challenged. The aim of this paper is to review the literature on de-escalation of RNI in patients treated with PST. We found no level 1 evidence on de-escalation of RNI after PST, but several randomized trials are ongoing. Consequently, current de-escalation strategies are based on cohort studies. These studies showed that in patients with low nodal tumour burden (LNTB) (≤3 suspicious nodes at imaging) prior to PST, and ypN0 based on Axillary Lymph Node Dissection (ALND), omission of RNI resulted in very low regional recurrences (RR) without compromising survival. In patients with LNTB and ypN0 based on Sentinel Lymph Node Biopsy (SLNB), omission of axillary treatment also resulted in low RR; the majority of these patients received local radiotherapy. Similarly, in patients with ypN1 (ALND) disease, omission of RNI resulted in low 5-year RR rates. Low RR-rates were also found in the few studies replacing ALND by RNI, in patients with ypN1 (SLNB) disease. In patients with high nodal tumour burden prior to PST and ypN0 (SLNB), replacing ALND by RNI also resulted in low RR. Due to the limited number of patients, these data should be interpreted with caution. We conclude that although level 1 evidence is lacking, de-escalation of RNI after PST can be considered in selected cases.