No Axillary Surgical Treatment in Clinically Lymph Node Negative Patients on Ultrasonography After Neoadjuvant Chemotherapy

Overview

NEO-NAUTILUS is a prospective, multicenter, randomized phase III clinical trial to evaluate whether omitting axillary lymph node surgery (ALND or SLNB) in clinically lymph node-negative breast cancer patients after neoadjuvant chemotherapy is non-inferior to performing SLNB in terms of 5-year disease-free survival.

Background: * No prospective studies have proven that axillary lymph node surgery improves survival in breast cancer patients. * The ACOSOG Z0011 trial showed that additional axillary dissection did not improve recurrence or survival, even with a 23.7% incidence of non-sentinel node metastases. * NSABP B-32 established the oncologic safety of SLNB, significantly reducing complications like lymphedema compared to axillary dissection. However, SLNB still carries risks of lymphedema, sensory changes, seromas, and infections. * The trend has now shifted toward identifying candidates for omitting axillary surgery to minimize unnecessary complications. * The SOUND trial demonstrated non-inferiority of omitting SLNB in early-stage breast cancer patients with negative axillary ultrasound. Five-year distant metastasis-free survival was comparable between SLNB and no-SLNB groups (97.7% vs. 98.0%). * Improved ultrasound accuracy (e.g., FNR: 13.7% in SOUND; 11.3% in NAUTILUS) and the therapeutic contribution of whole-breast radiation likely support these findings. * Patients with a complete pathological response (pCR) in the breast post-NAC rarely have residual lymph node metastases, reducing the need for axillary surgery. * Single-arm studies (e.g., EUBREAST-01, ASICS, ASLAN) have explored omitting axillary surgery in patients with confirmed breast pCR. However, these studies face limitations due to small sample sizes, single-arm design, and the necessity of axillary surgery if pCR is not achieved. * To address these limitations, the NEO-NAUTILUS trial proposes the first randomized trial to compare disease-free survival and local recurrence rates between patients who omit SLNB (experimental group) and those who undergo SLNB (control group) after NAC, focusing on patients deemed axillary node-negative by ultrasound.