Axillary lymph node dissection versus radiotherapy in breast cancer with positive sentinel nodes after neoadjuvant therapy (ADARNAT trial)

Abstract

IntroductionBreast cancer surgery currently focuses on de-escalating treatment without compromising patient survival. Axillary radiotherapy (ART) now replaces axillary lymph node dissection (ALND) in patients with limited sentinel lymph node (SLN) involvement during the primary surgery, and this has significantly reduced the incidence of lymphedema without worsening the prognosis. However, patients treated with neoadjuvant systemic treatment (NST) cannot benefit from this option despite the low incidence of residual disease in the armpit in most cases. Data regarding the use of radiotherapy instead of ALND in this population are lacking. This study will assess whether ART is non-inferior to ALND in terms of recurrence and overall survival in patients with positive SLN after NST, including whether it reduces surgery-related adverse effects.Methods and analysesThis multicenter, randomized, open-label, phase 3 trial will enroll 1660 patients with breast cancer and positive SLNs following NST in approximately 50 Spanish centers over 3 years. Patients will be stratified by NST regimen and nodal involvement (isolated tumoral cells or micrometastasis versus macrometastasis) and randomly assigned 1:1 to ART without ALND (study arm) or ALND alone (control arm). Level 3 and supraclavicular radiotherapy will be added in both arms. The primary outcome is the 5-year axillary recurrence determined by clinical and radiological examination. The secondary outcomes include lymphedema or arm dysfunction, quality of life based (EORTC QLQ-C30 and QLQ-BR23 questionnaires), disease-free survival, and overall survival.DiscussionThis study aims to provide data to confirm the efficacy and safety of ART over ALND in patients with a positive SLN after NST, together with the impact on morbidity.Ethics and disseminationThe Research Ethics Committee of Bellvitge University Hospital approved this trial (Protocol Record PR148/21, version 3, 1/2/2022) and all patients must provide written informed consent. The involvement of around 50 centers across Spain will facilitate the dissemination of our results.Trial registrationClinicalTrials.gov, identifier number NCT04889924.

Accuracy Rate of Methylene Blue Injection in Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer Patients: A Prospective Observational Study

“…without metastatic lymph nodes (cN0), 70-80% of these patients have pathologically cancer cell-free lymph nodes (pN0), increasing the risk of unnecessary procedures such as arm lymphedema, axillary sensory impairment, and shoulder adduction deficits. [28][29][30][31][32] This study found that the accuracy of SNLB compared to the histological examination from the axillary lymph node dissection showed a sensitivity of 82.8% and a specificity of 88%. This value is slightly different for patients who have had different types of biopsies.…”

Sentinel lymph node biopsy before and after neoadjuvant chemotherapy in cN0 breast cancer patients: impact on axillary morbidity and survival—a propensity score cohort study

“…However, there are two ongoing studies where patients who have SLNB positive after NACT are being randomized to receive either ALND or axillary radiotherapy. The results of the Alliance A011202 and the ADARNAT trial NCT04889924 [ 35 ] will be crucial to determine whether radiotherapy is non-inferior to ALND in terms of DFS and OS in patients with a positive SLNB after NACT. Research is ongoing in two trials: the Alliance A011202 and the ADARNAT trial NCT04889924.…”

Axillary Surgery for Breast Cancer in 2024

“…These patients are randomized to ART or ALND, with the primary endpoint being the non-inferiority of axillary recurrence. A pilot phase including 100 patients was finalized in April 2023, and the accrual of the planned total of 1660 patients is ongoing [138].…”