Axillary treatment options in clinically nodes-positive breast cancer whose nodes become pathologically nodes-negative after neoadjuvant chemotherapy: a pairwise and network meta-analysis

Neoadjuvant chemotherapy (NAC) has increased heterogeneity in regional axillary management. The optimal strategy remains uncertain for patients with clinically node-positive (cN+) breast cancer (BC) who convert to pathologically node-negative (ypN0) status after NAC. This study aimed to identify the most appropriate axillary treatment strategies for this subgroup. PubMed, Web of Science, Embase, and the Cochrane Library were searched for studies published up to July 2025. Pairwise meta-analysis and Bayesian network meta-analysis (NMA) were conducted in R to compare survival outcomes. The primary endpoints were overall survival (OS) and disease-free survival (DFS). Comparative efficacy was summarized using forest plots, league tables, and surface under the cumulative ranking curve (SUCRA) values. Twenty studies on 19,870 patients were analyzed. In pairwise comparisons, sentinel lymph node biopsy (SLNB) plus regional nodal irradiation (RNI) was associated with worse OS than SLNB alone (hazard ratio (HR): 1.28, 95% confidence interval (CI): 1.09–1.51; I2=0%). In the NMA, SLNB ranked highest for OS (SUCRA = 0.95), whereas axillary lymph node dissection (ALND) plus RNI ranked lowest (SUCRA = 0.17). For DFS, SUCRA values were similar across all strategies, indicating comparable efficacy. In patients with cN + BC who achieve ypN0 status after NAC, tailored axillary strategies yielded survival outcomes comparable to conventional approaches. SLNB ranked highest for OS in the NMA, supporting its role as an effective and less invasive option in appropriately selected patients. However, these findings are largely based on retrospective data. Prospective studies with long-term follow-up are needed for confirmation. This study provides the first Bayesian network meta-analysis (NMA) and the largest systematic review to date evaluating axillary management strategies after neoadjuvant chemotherapy (NAC) in patients with clinically node-positive (cN+) breast cancer (BC) who convert to pathologically node-negative (ypN0) status, addressing a long-standing clinical uncertainty.Tailored axillary approaches, particularly sentinel lymph node biopsy (SLNB), yielded survival outcomes similar to conventional treatments. SLNB was ranked highest for OS in the NMA, supporting its role as an effective, less invasive option in appropriately selected patients. This study provides the first Bayesian network meta-analysis (NMA) and the largest systematic review to date evaluating axillary management strategies after neoadjuvant chemotherapy (NAC) in patients with clinically node-positive (cN+) breast cancer (BC) who convert to pathologically node-negative (ypN0) status, addressing a long-standing clinical uncertainty. Tailored axillary approaches, particularly sentinel lymph node biopsy (SLNB), yielded survival outcomes similar to conventional treatments. SLNB was ranked highest for OS in the NMA, supporting its role as an effective, less invasive option in appropriately selected patients.