Diagnostic Accuracy of Radioactive Iodine Seed Placement in the Axilla With Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Node-Positive Breast Cancer

Abstract

Importance: Several less-invasive staging procedures have been proposed to replace axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC) in patients with initially clinically node-positive (cN+) breast cancer, but these procedures may fail to detect residual disease. Owing to the lack of high-level evidence, it is not yet clear which procedure is most optimal to replace ALND.

Objective: To determine the diagnostic accuracy of radioactive iodine seed placement in the axilla with sentinel lymph node biopsy (RISAS), a targeted axillary dissection procedure.

Design, setting, and participants: This was a prospective, multicenter, noninferiority, diagnostic accuracy trial conducted from March 1, 2017, to December 31, 2019. Patients were included within 14 institutions (general, teaching, and academic) throughout the Netherlands. Patients with breast cancer clinical tumor categories 1 through 4 (cT1-4; tumor diameter <2 cm and up to >5 cm or extension to the chest wall or skin) and pathologically proven positive axillary lymph nodes (ie, clinical node categories cN1, metastases to movable ipsilateral level I and/or level II axillary nodes; cN2, metastases to fixed or matted ipsilateral level I and/or level II axillary nodes; cN3b, metastases to ipsilateral level I and/or level II axillary nodes with metastases to internal mammary nodes) who were treated with NAC were eligible for inclusion. Data were analyzed from July 2020 to December 2021.

Intervention: Pre-NAC, the marking of a pathologically confirmed positive axillary lymph node with radioactive iodine seed (MARI) procedure, was performed and after NAC, sentinel lymph node biopsy (SLNB) combined with excision of the marked lymph node (ie, RISAS procedure) was performed, followed by ALND.

Main outcomes and measures: The identification rate, false-negative rate (FNR), and negative predictive value (NPV) were calculated for all 3 procedures: RISAS, SLNB, and MARI. The noninferiority margin of the observed FNR was 6.25% for the RISAS procedure.

Results: A total of 212 patients (median [range] age, 52 [22-77] years) who had cN+ breast cancer underwent the RISAS procedure and ALND. The identification rate of the RISAS procedure was 98.2% (223 of 227). The identification rates of SLNB and MARI were 86.4% (197 of 228) and 94.1% (224 of 238), respectively. FNR of the RISAS procedure was 3.5% (5 of 144; 90% CI, 1.38-7.16), and NPV was 92.8% (64 of 69; 90% CI, 85.37-97.10), compared with an FNR of 17.9% (22 of 123; 90% CI, 12.4%-24.5%) and NPV of 72.8% (59 of 81; 90% CI, 63.5%-80.8%) for SLNB and an FNR of 7.0% (10 of 143; 90% CI, 3.8%-11.6%) and NPV of 86.3% (63 of 73; 90% CI, 77.9%-92.4%) for the MARI procedure. In a subgroup of 174 patients in whom SLNB and the MARI procedure were successful and ALND was performed, FNR of the RISAS procedure was 2.5% (3 of 118; 90% CI, 0.7%-6.4%), compared with 18.6% (22 of 118; 90% CI, 13.0%-25.5%) for SLNB (P < .001) and 6.8% (8 of 118; 90% CI, 3.4%-11.9%) for the MARI procedure (P = .03).

Conclusions and relevance: Results of this diagnostic study suggest that the RISAS procedure was the most feasible and accurate less-invasive procedure for axillary staging after NAC in patients with cN+ breast cancer.

Figure 1.. Consolidated Standards of Reporting Trials (CONSORT) Diagram and Flowchart

A, CONSORT diagram for the radioactive iodine seed placement in the axilla with sentinel lymph node biopsy (RISAS) procedure. B, Flowchart of patients who underwent sentinel lymph node biopsy (SLNB) and the marking of a pathologically confirmed positive axillary lymph node with radioactive iodine seed (MARI) procedure. In 3 of 9 patients with lymph node–negative (ypN0) status based on SLNB, residual disease was found in the MARI node. ALND indicates axillary lymph node dissection; cN+, clinically node positive; FN, false negative; NAC, neoadjuvant chemotherapy; TN, true negative; TP, true positive; ypN+, lymph node metastasis. ^aAt the patients’ request, only the RISAS procedure without completion ALND was performed (this decision was always made before the surgical procedure took place). ^bThese numbers represent all patients in whom SLNB was performed (ie, RISAS procedure in 227 patients and SLNB only [without MARI] in 1 patient for a total of 228 patients for SLNB) or in whom the MARI procedure was performed (ie, RISAS procedure in 227 patients and MARI only [without SLNB] in 11 patients for a total of 238 patients for MARI).

Figure 2.. Digital Hematoxylin and Eosin–Stained Tissue Sections From a Radioactive Iodine Seed Placement in the Axilla With Sentinel Lymph Node Biopsy (RISAS) Lymph Node That Underwent Central Pathology Review

A, The original on-site section without signs of residual disease. B, An additional section obtained at central pathology review with a large cluster (>2 mm) of residual cancer cells (arrowhead). C, Magnification of the cluster of residual cancer cells from panel (B).