Abstract Background: Axillary lymph node dissection (ALND) remains the standard of care for patients with breast cancer with residual nodal disease (ypN+) after neoadjuvant chemotherapy (NAC). While the results of randomized controlled trials on the safety of omitting ALND are still awaited, retrospective studies suggest that de-escalation is already incorporated into clinical practice. This systematic review and meta-analysis aimed to evaluate oncological outcomes of sentinel lymph node biopsy (SLNB) alone versus ALND in patients with residual nodal disease after NAC. Methods: A systematic search of PubMed, Embase, and the Cochrane Library was performed. Eligible studies included randomized controlled trials and observational cohort studies of patients with clinically node-positive breast cancer who received NAC and were found to have ypN+ disease at surgery. Studies reporting outcomes of axillary recurrence, distant recurrence-free survival (DRFS), and/or overall survival (OS) were included. Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing SLNB to ALND were extracted or estimated from Kaplan-Meier curves using validated methods. A random-effects meta-analysis was conducted. Results: Nine retrospective studies encompassing a total of 13,160 patients were included in the analysis. Of these, 3,831 patients underwent SLNB alone, while 9,329 underwent ALND. Axillary recurrence outcomes were reported in six studies. The pooled axillary recurrence rate was 5.91% (95% CI: 3.47%-9.92%) in the SLNB group and 5.24% (95% CI: 3.66%-7.44%) in the ALND group. SLNB was associated with a statistically significant reduction in axillary recurrence compared to ALND (HR = 0.94, 95% CI: 0.90-0.99), although the difference may not be clinically meaningful. Five studies reported DRFS with no significant difference between SLNB and ALND (HR = 0.99, 95% CI: 0.83-1.18), though substantial heterogeneity was present (I2 = 69.7%), suggesting variability that may affect outcomes. Eight studies reported OS outcomes and no significant difference in OS between the two groups (HR = 1.08, 95% CI: 0.94-1.24, p = 0.26). Notably, all these findings may reflect selection bias, as patients selected for SLNB alone may have been more likely to have favorable baseline characteristics. Conclusion: This meta-analysis of retrospective studies suggests that omission of ALND in ypN+ patients does not compromise axillary control and may be associated with comparable regional and distant control with similar survival. However, due to the inherent limitations of retrospective data—including potential selection bias and unmeasured confounding—these findings should be interpreted with caution. Prospective randomized trials are necessary to confirm the safety of omitting ALND and to identify which patients may be appropriate candidates for axillary surgery de-escalation. Citation Format: N. Polidorio, R. Frederice, G. Azevedo Gabriele Carlos, T. Dassie, R. Sousa-Barroso. De-escalation of Axillary Surgery in Patients with Residual Nodal Disease After Neoadjuvant Chemotherapy: A Systematic Review and Meta-Analysis abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-03-24.
Polidorio et al. (Tue,) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: