Carbon (charcoal) tattoo localization of biopsy-proven metastatic axillary lymph nodes for targeted axillary dissection after neoadjuvant therapy in breast cancer: a systematic review and single -arm meta-analysis

BACKGROUND: Targeted axillary dissection (TAD) using carbon tattooing aims to localize and excise biopsy-proven metastatic axillary nodes after neoadjuvant systemic therapy (NAST), potentially improving post-NAST axillary staging while enabling the de-escalation of axillary surgery. METHODS: We systematically searched Scopus, Embase, PubMed, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov, supplemented by screening reference lists. Prospective and retrospective clinical studies evaluating carbon tattooing-guided targeted tattooed lymph node (TLN) excision in initially node-positive breast cancer patients treated with NAST were included. Random-effects generalized linear mixed models (GLMM) were used to pool the proportions of dichotomous outcomes. Continuous outcomes were pooled using a random-effects inverse variance model. The risk of bias was assessed using the ROBINS-I tool. Leave-one-out sensitivity analyses and a pre-specified clinical subgroup analysis (completion-ALND verification cohort vs. feasibility/no-mandatory-ALND cohort) were also performed. RESULTS: Nine studies were included in this review. The pooled TLN identification rate was 0.94 (95% CI: 0.88-0.97). The pooled sentinel lymph node (SLN) identification rate was 0.754 (95% CI 0.541-0.888), with substantial heterogeneity between studies. TLN-SLN concordance was 0.554 (95% CI 0.333-0.755), indicating a moderate overlap between the tattooed node and SLN. In the completion-ALND verification cohorts, the pooled false-negative rate (FNR) of the targeted procedure versus ALND for residual nodal disease was 0.068 (95% CI 0.042-0.108). The pooled mean number of retrieved nodes was 3.25 (95% CI 2.54-3.96), and the pooled tattoo-to-surgery interval was 153.0 days (95% CI 131.9-174.2). Sensitivity analyses showed that no single study unduly influenced pooled estimates. CONCLUSION: Carbon tattooing-guided targeted axillary procedures after NAST demonstrated high TLN retrieval and low verification-cohort FNR, supporting procedural feasibility for post-NAST axillary staging in initially node-positive breast cancer patients. However, variable SLN identification, moderate TLN-SLN concordance, and heterogeneity in technique and reporting support implementation within standardized multidisciplinary workflows with local audits. Further prospective comparative studies are required.