Abstract PD4-01: Preservation of axillary lymph nodes compared to complete dissection in T1-T2 breast cancer patients presenting 1-2 metastatic sentinel lymph nodes : A multicenter randomized clinical trial. Sinodar One.

Abstract

Introduction: Sentinel lymph node (SLN) staging is currently used to avoid complete axillary lymph node dissection (ALND) in breast cancer (BC) patients. The SLN is the only site of axillary metastasis (MTS) in ≤60% of cases. Recently, a randomized controlled trial (Z0011) comparing SLN biopsy (SLNB) alone with SLNB followed by ALND in patients with 1-2 SLNs+ demonstrated no significant statistical difference in relapse and overall survival rates among the two different groups. However, this study had some limitations: small tumor size (≤2cm in 70% of cases), frequent presence of only microMTS in SLN (40%), prevalent use of “whole breast” adjuvant radiotherapy (>90%). Given these considerations, the SINODAR-ONE study started in April 2015.Objectives: The aims are to assess whether ALND omission in BC patients with 1-2 SLNs+ is associated with worse survival and/or increased rate of regional/distant relapse. Thus evaluating whether SLNB is or is not inferior to ALND. Primary endpoint is overall survival (OS). Secondary endpoints are disease-free survival (DFS) referring to distant MTS and loco-regional recurrence. Methods: Patients receive either mastectomy or conservative surgery plus radiotherapy. They all undergo SLNB and are randomly divided into two arms of treatment: standard (SLNB plus ALND) or experimental treatment (only SLNB). According to multidisciplinary evaluation, patients may undergo additional adjuvant radiotherapy, chemo- and/or hormonal therapy , or no further therapy. Eligibility criteria: age 40-75 years; primary invasive T1-T2 tumor; axillary nodes clinically N0; no more than 2 macro-metastatic SLNs; no distant MTS; no neo-adjuvant therapy; no previous invasive BC; signed informed consent. Exclusion criteria: in situ, inflammatory, contralateral BC; micro-metastic SLNs; pregnancy or breast feeding; comorbidity impeding adjuvant therapy. All analyses are performed both on all patients according to the Intention-To-Treat principle and excluding those patients who did not receive the axillary treatment randomly assigned. Statistical analysis: OS and DFS are calculated using the Kaplan-Meier Product Limit Estimator and differences between arms are assessed with the log-rank test. Results: The enrollment of patients ended in April 2020 with a total of 889 cases (443: standard arm; 446: experimental arm). In June 2020, we conducted an ad interim analysis on 889 patients. We found the two groups homogeneous for epidemiologic characteristics (age and menopausal status), tumor characteristics (tumor size, pTNM, immunohistochemistry, histology, grading, vascular and lymphatic invasion), adjuvant therapies and surgery on T. In particular we have performed a 23,1% of mastectomies in the standard arm and 20,1% in the experimental arm. We found a median of 2 sentinel lymph nodes removed in both arms and 1 non-sentinel positive lymph node in the experimental arm, and only 3 micro-metastases (1 in the standard arm and 2 in the experimental arm). Conclusion: In sum, with a median follow-up of 30 months, there have been no axillary recurrence in both arms. In the standard arm we found 8 total events (2 deaths and 6 distant relapses) and in in the experimental arm 6 events (1 death and 5 distant relapses), with a projected 5-years cumulative incidence of 6,5% in standard arm and 4,85% in the experimental arm. Citation Format: Corrado Tinterri, Emilia Marrazzo, Chiara Anghelone, Erika Barbieri, Andrea Sagona, Alberto Bottini, Arianna Rubino, Damiano Gentile, Wolfgang Gatzemeier, Valentina Errico, Alberto Testori, Giuseppe Canavese. Preservation of axillary lymph nodes compared to complete dissection in T1-T2 breast cancer patients presenting 1-2 metastatic sentinel lymph nodes : A multicenter randomized clinical trial. Sinodar One. [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD4-01.

Real de-escalation or escalation in disguise?

“…Recently, SINODAR-ONE, a trial with a similar design as Z0011, reached similar conclusions [39]. In contrast to Z0011, only patients with macrometastases were enrolled and mastectomy was not an exclusion criterion.…”

“…ACOSOG Z0011 [37] AMAROS [38] SINODAR-ONE [39] OTOASOR [40] Patient number Abbreviations: DMFSdistant metastasis-free survival.…”

Sentinel lymph node biopsy following neoadjuvant chemotherapy: an evidence-based review and recommendations for current practice

“…Indeed, the Z11 study showed excellent locoregional control with the omission of additional axillary surgery in patients with positive SLN. However, as in other studies that also evaluated the omission of axillary dissection at upfront surgery, patients submitted to NACT were not included in those analyses (45)(46)(47)(48)(49). Furthermore, residual disease following NACT means resistance to systemic treatment, hence the possibility of a high residual burden of disease.…”

Recommendations for the diagnosis and treatment of patients with early breast cancer: update 2023

“…It should be performed in all patients with clinically and sonographically inconspicuous ALN status (cN0). The indication for ALND is increasingly limited to patients with high axillary tumour burden after several randomized trials failed to show an advantage for ALND in low, clinically occult tumour burden [45][46][47]. However, for these patients, there appears to be a benefit from radiotherapy of the axilla.…”