The efficacy and oncological safety of minimally invasive axillary procedures in patients with node-positive breast cancer receiving neoadjuvant chemotherapy: A network meta-regression and trial sequential analysis.

Background: Neoadjuvant chemotherapy (NAC) can downstage axillary nodes in breast cancer, prompting debate over the optimal axillary management after NAC. While axillary dissection (ALND) provides detailed assessment of node status, minimally invasive methods such as sentinel lymph node biopsy (SLNB), marked lymph node biopsy (MLNB) and targeted axillary dissection (TAD) are showing promise. This meta-analysis aims to assess the efficacy and safety of these strategies.

Methods: A systematic search of Medline, Embase and Cochrane Central was conducted and relevant RCTs were identified. Random-effects meta-analysis, meta-regression and trial sequential analysis (TSA) were conducted for diagnostic outcomes (identification rates [IFR], false negative rates [FNR] and negative predictive value [NPV]) and survival outcomes (overall survival [OS], disease-free survival [DFS]) to compare SLNB, MLNB and TAD with ALND.

Results: Twenty-eight studies (SLNB, n = 3392; MLNB, n = 1130; TAD, n = 946) investigated diagnostic outcomes and nine studies investigated survival outcomes (n = 5647). The pooled IFR, FNR and NPV of TAD was 96.8 %, 4.7 % and 93.2 %, respectively, and all values were superior to SLNB (91.9 %, 13.7 % and 84.8 %; meta-regression, p < 0.001) (SLNB vs. MLNB concordance = 73 %). The FNR of SLNB decreased with the number of nodes removed (≥3 nodes, 8.1 %) but remained inferior to TAD (p = 0.001). The IFR of SLNB in the ycN0 group was statistically lower than all patients (ycN0/+), 85.8 % vs. 91.9 % (p < 0.001). Pooled hazard ratios for DFS in SLNB/TAD, SLNB and TAD were 0.90 (95%CI, 0.77-1.04; p = 0.45), 0.89 (95%CI, 0.74-1.08; p = 0.25) and 0.91 (95%CI, 0.64-1.29; p = 0.58) (TSA 2.08>threshold). Indirect comparison between TAD and SLNB demonstrated no significant difference in DFS (HR 0.98; 0.64-1.32; 95%CI, p = 0.95).

Conclusions: Targeted axillary dissection is the optimal minimally invasive axillary technique in terms of diagnostic accuracy. De-escalation of axillary surgery following NAC does not negatively impact DFS in patients with node-positive breast cancer.