Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer: Results of the randomised controlled EORTC 10981-22023 AMAROS trial

Introduction: If treatment of the axilla is indicated in breast cancer patients with a positive sentinel node (SN), axillary lymph node dissection (ALND) is the current standard. Though ALND provides excellent regional control, it is associated with harmful side effects. Axillary radiotherapy (ART) was hypothesized to provide comparable regional control with fewer side effects. Methods: From 2001 to 2010, 4806 patients with cT1-2N0 primary breast cancer were enrolled in the EORTC phase III non-inferiority AMAROS trial. Patients were randomised between ALND and ART in case of a positive SN. The primary endpoint was 5-year axillary recurrence rate. Secondary endpoints were disease-free survival (DFS), overall survival (OS), shoulder mobility and lymphoedema at 1 and 5 years, and quality of life (QoL). The AMAROS trial is registered, Clinicaltrials.gov Identifier: NCT00014612. Findings: After a positive SN, 744 patients were randomised to the ALND-group and 681 to the ART-group. With a median follow up of 6.1 years, the 5-year axillary recurrence rate was 0.43% after ALND versus 1.19% after ART. The planned non-inferiority test was underpowered because of the unexpectedly low number of events. The 5-year axillary recurrence rate after a negative SN was 0.72%. There were no significant differences between treatment groups regarding OS (5-yr estimates: 93.3% ALND, 92.5% ART, p = 0.339) and DFS (5-yr estimates: 86.9% ALND, 82.7% ART, p = 0.179). Lymphoedema related problems were found significantly more often after ALND (1 yr: 40.0% ALND, 21.7% ART, p < 0.001 and 5 yr: 28.0% ALND, 13.6% ART, p < 0.001). There was no significant difference in shoulder mobility (1 yr: p = 0.289, 5 yr: p = 0.468), and no significant difference in QoL. Interpretation: ALND and ART after a positive SN provide excellent and comparable axillary control. The incidence of lymphoedema was significantly lower after ART than after ALND. ART should be considered recommended treatment for these patients..