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

Author(s): Toralf Reimer, Ph.D.¹, Angrit Stachs, Ph.D.¹, Kristina Veselinovic, M.D.², Thorsten Kühn, Ph.D.³, Jörg Heil, Ph.D.^4,5 https://orcid.org/0000-0002-4684-9099, Silke Polata, M.D.⁶, Frederik Marmé, Ph.D.⁷, Thomas Müller, Ph.D.⁸, Guido Hildebrandt, Ph.D.⁹, David Krug, Ph.D.^10,11, Beyhan Ataseven, Ph.D.¹², Roland Reitsamer, Ph.D.¹³, Sylvia Ruth, M.D.¹⁴, Carsten Denkert, Ph.D.¹⁵, Inga Bekes, Ph.D.^2,16, Dirk-Michael Zahm, M.D.¹⁷, Marc Thill, Ph.D.¹⁸, Michael Golatta, Ph.D.^4,5, Johannes Holtschmidt, M.D.¹⁹, Michael Knauer, Ph.D.²⁰, Valentina Nekljudova, Ph.D.¹⁹, Sibylle Loibl, Ph.D.¹⁹, and Bernd Gerber, Ph.D.¹

Source: DOI: 10.1056/NEJMoa2412063

Dr. Anjan Patel's Thoughts

The INSEMA trial showed that for early stage, T1-T2 clinically node negative breast cancer, sentinel lymph node biopsies should not be mandatory, and best clinical judgement can be used.

Background

Whether surgical axillary staging as part of breast-conserving therapy can be omitted without compromising survival has remained unclear.

Methods

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.

Results

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.

Conclusions

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.)

Author Affiliations

¹ Department of Obstetrics and Gynecology, University of Rostock, Rostock, Germany; ² University Hospital Ulm, Ulm, Germany; ³ Hospital Esslingen, Esslingen, Germany; ⁴ University Hospital Heidelberg, Heidelberg, Germany; ⁵ Breast Unit, Sankt Elisabeth Hospital, Heidelberg, Germany; ⁶ Evang. Waldkrankenhaus Spandau, Berlin; ⁷ Faculty of Medicine Mannheim, Department of Obstetrics and Gynecology, University of Heidelberg, Mannheim, Germany; ⁸ Department of Obstetrics and Gynecology, Hanau City Hospital, Hanau, Germany; ⁹ Department of Radiation Oncology, University Hospital Rostock, Rostock, Germany; ¹⁰ Department of Radiotherapy and Radiation Oncology, University Hospital Hamburg-Eppendorf (UKE), Hamburg, Germany; ¹¹ Department of Radiation Oncology, University Medical Center Schleswig-Holstein, Kiel, Germany; ¹² Medical School and University Medical Center OWL, Department of Gynecology and Obstetrics, Bielefeld University, Klinikum Lippe, Detmold, Germany; ¹³ Salzburg Regional Hospital, Salzburg, Austria; ¹⁴ Johanniter Hospital Genthin-Stendal, Stendal, Germany; ¹⁵ Institute of Pathology, Philipps University Marburg and University Hospital Marburg (UKGM), Marburg, Germany; ¹⁶ Breast Center St. Gallen, Kantonsspital St. Gallen, St. Gallen, Switzerland; ¹⁷ SRH Wald-Klinikum Gera, Gera, Germany; ¹⁸ Department of Gynecology and Gynecologic Oncology, Agaplesion Markus Hospital, Frankfurt am Main, Germany; ¹⁹ German Breast Group, Neu-Isenburg, Germany; ²⁰ Tumor and Breast Center Eastern Switzerland, St. Gallen, Switzerland

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