Journal Article

Axillary Surgery in Breast Cancer — Primary Results of the INSEMA Trial

Thill, Marc, Bekes, Inga, Holtschmidt, Johannes, Reitsamer, Roland, Denkert, Carsten, Veselinovic, Kristina, Müller, Thomas, Stachs, Angrit, Hildebrandt, Guido, Ruth, Sylvia, Krug, David, Ataseven, Beyhan, Kühn, Thorsten, Gerber, Bernd, Loibl, Sibylle, Reimer, Toralf, Marmé, Frederik, Nekljudova, Valentina, Heil, Jörg, Golatta, Michael, Polata, Silke, Zahm, Dirk-Michael, Knauer, Michael

2025

Overview

Whether surgical axillary staging as part of breast-conserving therapy can be omitted without compromising survival has remained unclear. In this prospective, randomized, noninferiority trial, we investigated the omission of axillary surgery as compared with sentinel-lymph-node biopsy in patients with clinically node-negative invasive breast cancer staged as T1 or T2 (tumor size, ≤5 cm) who were scheduled to undergo breast-conserving surgery. We report here the per-protocol analysis of invasive disease-free survival (the primary efficacy outcome). To show the noninferiority of the omission of axillary surgery, the 5-year invasive disease-free survival rate had to be at least 85%, and the upper limit of the confidence interval for the hazard ratio for invasive disease or death had to be below 1.271. A total of 5502 eligible patients (90% with clinical T1 cancer and 79% with pathological T1 cancer) underwent randomization in a 1:4 ratio. The per-protocol population included 4858 patients; 962 were assigned to undergo treatment without axillary surgery (the surgery-omission group), and 3896 to undergo sentinel-lymph-node biopsy (the surgery group). The median follow-up was 73.6 months. The estimated 5-year invasive disease-free survival rate was 91.9% (95% confidence interval [CI], 89.9 to 93.5) among patients in the surgery-omission group and 91.7% (95% CI, 90.8 to 92.6) among patients in the surgery group, with a hazard ratio of 0.91 (95% CI, 0.73 to 1.14), which was below the prespecified noninferiority margin. The analysis of the first primary-outcome events (occurrence or recurrence of invasive disease or death from any cause), which occurred in a total of 525 patients (10.8%), showed apparent differences between the surgery-omission group and the surgery group in the incidence of axillary recurrence (1.0% vs. 0.3%) and death (1.4% vs. 2.4%). The safety analysis indicates that patients in the surgery-omission group had a lower incidence of lymphedema, greater arm mobility, and less pain with movement of the arm or shoulder than patients who underwent sentinel-lymph-node biopsy. In this trial involving patients with clinically node-negative, T1 or T2 invasive breast cancer (90% with clinical T1 cancer and 79% with pathological T1 cancer), omission of surgical axillary staging was noninferior to sentinel-lymph-node biopsy after a median follow-up of 6 years. (Funded by the German Cancer Aid; INSEMA ClinicalTrials.gov number, NCT02466737.).

• Publisher: Massachusetts Medical Society
• Subject: Adult / Aged / Aged, 80 and over / Arm / Axilla - pathology / Axilla - surgery / Biopsy / Breast Cancer / Breast Cancer Lymphedema - epidemiology / Breast Cancer Lymphedema - etiology / Breast Cancer Lymphedema - prevention & control / Breast Neoplasms - diagnosis / Breast Neoplasms - mortality / Breast Neoplasms - pathology / Breast Neoplasms - surgery / Breast surgery / Cancer therapies / Clinical outcomes / Death / Disease-Free Survival / Dissection / Female / Follow-Up Studies / Hematology / Humans / Incidence / Invasiveness / Kaplan-Meier Estimate / Lumpectomy / Lymph / Lymphatic Metastasis / Lymphatic system / Lymphedema / Mammography / Mastectomy, Segmental - methods / Mastectomy, Segmental - statistics & numerical data / Medical prognosis / Medical research / Middle Aged / Neoplasm Recurrence, Local - epidemiology / Neoplasm Recurrence, Local - prevention & control / Neoplasm Staging - adverse effects / Neoplasm Staging - methods / Oncology / Patients / Prospective Studies / Quality of life / Questionnaires / Radiation therapy / Sentinel Lymph Node Biopsy - adverse effects / Sentinel Lymph Node Biopsy - methods / Sentinel Lymph Node Biopsy - statistics & numerical data / Statistical analysis / Surgery / Surgery General / Surgical outcomes / Survival / Treatments in Oncology / Ultrasonic imaging / Young Adult