Radiotracer-Free Axillary Staging with ICG and Methylene Blue After Neoadjuvant Chemotherapy: Does Failure to Retrieve the Clipped Node Matter?

Background: Radiotracer- and magnetic seed-based targeted axillary staging techniques are increasingly used after neoadjuvant chemotherapy (NAC) in patients with initially node-positive breast cancer who convert to clinical node-negative (ycN0) status. However, these technologies remain unavailable in many centres worldwide. We evaluated the effectiveness of radiotracer-free axillary staging using dual-tracer sentinel lymph node biopsy (SLNB) with indocyanine green (ICG) and methylene blue, with particular focus on the clinical implications of clipped node non-retrieval. Methods: This retrospective single-centre cohort study included 49 patients with biopsy-proven cN1 breast cancer who achieved ycN0 status following NAC and underwent dual-tracer SLNB using ICG and methylene blue between 2021 and 2024. Clipped node retrieval rates, tracer-specific detection patterns, recurrence outcomes, and disease-free survival (DFS) were analysed. Clinical outcomes, including recurrence and disease-free survival, were compared between patients with successful and unsuccessful clipped node retrieval. Results: Clipped node retrieval was achieved in 41 of 49 patients (83.7%). ICG outperformed methylene blue for clipped node identification (80.5% vs. 61.0%) and was the sole detecting tracer in 39.0% of cases. Using methylene blue alone would have reduced the retrieval rate to 51.0% (p = 0.001). ICG identified the clipped node in all six patients with axillary micrometastases (ypN1mi). Clipped node non-retrieval occurred in eight patients, all of whom had negative SLNB findings and did not undergo completion axillary lymph node dissection. Recurrence rates were similar between the retrieval and non-retrieval groups (17.1% vs. 12.5%, p = 1.000), and no isolated axillary recurrences were observed. Baseline tumour size was the only independent predictor of disease-free survival in multivariable analysis (HR 2.05, 95% CI 1.20–3.51; p = 0.008). Conclusions: Radiotracer-free axillary staging using ICG and methylene blue achieved a high clipped node retrieval rate in patients with ycN0 breast cancer after neoadjuvant chemotherapy. ICG significantly improved clipped node identification compared with methylene blue alone and identified the clipped node in all patients with residual nodal micrometastatic disease. Among patients with negative SLNB findings, clipped node non-retrieval was not associated with higher recurrence rates or worse disease-free survival during follow-up. However, given the small number of clipped node non-retrieval cases (n = 8) and recurrence events (n = 8), these findings should be interpreted with caution and require confirmation in larger prospective studies. These findings support the feasibility of a radiotracer-free dual-tracer approach in settings where radiotracer-based techniques are not available. Prospective multicentre studies are warranted to validate both the oncological performance of radiotracer-free axillary staging and the clinical implications of clipped node non-retrieval.