Background: Axillary lymph node dissection (ALND) causes arm-related morbidity. The SENOMAC trial evaluates whether the omission of completion ALND in patients with 1-2 sentinel lymph node (SLN) macrometastases is oncologically safe. It differs from previous trials in size and the inclusion of larger tumors and patients receiving mastectomy.

Methods: SENOMAC (NCT02240472) is an international non-inferiority trial. Adult patients with primary invasive, clinically node-negative T1-3 breast cancer and up to two SLN macrometastases were randomized 1:1 to completion ALND (standard) or its omission (intervention). Adjuvant treatment followed standards of care. The primary endpoint was overall survival (OS), requiring 190 deaths to conclude non-inferiority (upper one-sided 90% CI for the hazard ratio , 1.44) with ALND as the reference group. The secondary endpoint breast cancer-specific survival (BCSS) required 66 breast cancer deaths. Patient-reported outcomes were recorded 1, 3, and 5 years after randomization by the questionnaires Lymph-ICF (arm morbidity), EORTC QLQ-C30 and BR23 (health-related quality of life).

Results: From 1/2015 to 12/2021, 2766 patients were randomized in 5 countries. The per-protocol population comprised 2540 patients (1205 randomized to ALND and 1335 to its omission). The median follow-up was 60.1 months (1.5-122.7 months). Questionnaire response rates were 81.3% and 74.6% at 3 and 5 years, respectively. Overall, 196 patients died, 75 of whom due to breast cancer. Five-year OS was 93.4% (95% CI 91.9%-94.9%) in the ALND and 94.4% (95% CI 93.1%-95.7%) in the omission group, with a country-adjusted hazard ratio of 0.84 (95% CI 0.64-1.12). Five-year BCSS was 97.3% (95% CI 96.4%-98.3%) in the ALND and 97.8% (95% CI 97.0%-98.6%) in the omission group, with a country-adjusted hazard ratio of 0.86 (95% CI 0.55-1.34). Both endpoints fell significantly (p = 0.238 for OS and p = 0.504 for BCSS) below the pre-specified non-inferiority margin. Arm physical function according to the Lymph-ICF questionnaire was significantly better in the omission than the ALND group with a clinically relevant mean score difference of 6.14 at 3 years (95% CI 5.00-7.43, p , 0.001) and 5.71 at 5 years (95% CI 4.46-7.25, p , 0.001). Similarly, arm symptoms according to EORTC QLQ-BR23 were significantly more pronounced in the ALND than the omission group both after 3 (mean score 20.80+/-21.24 versus mean score 10.83+/-15.48, p , 0.001) and after 5 years (mean score 19.40+/-21.07 versus mean score 9.31+/-15.58, p , 0.001). Global health-related quality of life did not show any statistically significant differences after 3 and 5 years.

Conclusions: Omission of completion ALND after a positive SLN biopsy is oncologically safe and mitigates postoperative patient-reported arm morbidity.

Clinical trial information: NCT02240472.