Noninferiority RCT: Omitting Sentinel-Lymph-Node Biopsy Maintains 5-Year Invasive Disease–Free Survival in Early-Stage Breast Cancer
13 Dec, 2024 | 15:15h | UTCBackground: While axillary surgical staging using sentinel-lymph-node biopsy has been a mainstay in early-stage breast cancer management, its necessity in clinically node-negative patients undergoing breast-conserving therapy has been called into question. With tumor biology increasingly guiding treatment decisions, reducing surgical interventions without compromising survival is a major goal.
Objective: To determine whether omitting sentinel-lymph-node biopsy in patients with clinically node-negative, T1 or T2 (≤5 cm) invasive breast cancer undergoing breast-conserving surgery is noninferior to performing sentinel-lymph-node biopsy in terms of 5-year invasive disease–free survival.
Methods: In this prospective, randomized, noninferiority trial, 5502 eligible patients were randomized in a 1:4 ratio to omission of axillary surgery versus sentinel-lymph-node biopsy. The per-protocol population included 4858 patients. All patients received whole-breast irradiation. Invasive disease–free survival, defined as time to any invasive disease event or death, was the primary endpoint. Noninferiority required a 5-year invasive disease–free survival rate ≥85% and a hazard ratio upper limit <1.271.
Results: After a median follow-up of 73.6 months, the 5-year invasive disease–free survival was 91.9% (95% CI, 89.9–93.5) in the omission group and 91.7% (95% CI, 90.8–92.6) in the sentinel-biopsy group (HR, 0.91; 95% CI, 0.73–1.14), meeting noninferiority criteria. Axillary recurrences were slightly higher in the omission group (1.0% vs. 0.3%), though without detrimental effects on overall survival. Patients who omitted axillary surgery experienced lower rates of lymphedema, better arm mobility, and less pain than those undergoing sentinel-lymph-node biopsy.
Conclusions: For appropriately selected patients with clinically node-negative, early-stage breast cancer undergoing breast-conserving surgery, omitting sentinel-lymph-node biopsy did not compromise 5-year invasive disease–free survival and yielded fewer surgical complications and better quality of life outcomes.
Implications for Practice: Omitting axillary staging may be considered in low-risk patients, particularly older individuals with small, hormone receptor-positive, HER2-negative tumors. However, clinicians should balance the lack of nodal information against potential alterations in adjuvant therapy decisions, especially regarding radiotherapy and systemic treatment recommendations.
Study Strengths and Limitations: Strengths include a large patient population, rigorous prospective randomization, and substantial follow-up. Limitations include a predominance of low-risk, small, HR-positive/HER2-negative tumors, potentially limiting generalizability. While omitting sentinel-lymph-node biopsy reduces surgical morbidity, the absence of nodal status may influence adjuvant treatment planning.
Future Research: Further studies should assess the applicability of omission strategies to younger patients, larger tumors, or more aggressive subtypes, and explore whether novel biomarkers or imaging methods can reliably guide treatment decisions without axillary surgery.