Technical outcomes of sentinel-lymph-node resection and conventional axillary-lymph-node dissection in patients with clinically node-negative breast cancer: results from the NSABP B-32 randomised phase III trial

Summary

Background

The goals of axillary-lymph-node dissection (ALND) are to maximise survival, provide regional control, and stage the patient. However, this technique has substantial side-effects. The purpose of the B-32 trial is to establish whether sentinel-lymph-node (SLN) resection can achieve the same therapeutic goals as conventional ALND but with decreased side-effects. The aim of this paper is to report the technical success and accuracy of SLN resection plus ALND versus SLN resection alone.

Methods

5611 women with invasive breast cancer were randomly assigned to receive either SLN resection followed by immediate conventional ALND (n=2807; group 1) or SLN resection without ALND if SLNs were negative on intraoperative cytology and histological examination (n=2804; group 2) in the B-32 trial. Patients in group 2 underwent ALND if no SLNs were identified or if one or more SLNs were positive on intraoperative cytology or subsequent histological examination. Primary endpoints, including survival, regional control, and morbidity, will be reported later. Secondary endpoints are accuracy and technical success and are reported here. This trial is registered with the Clinical Trial registry, number NCT00003830.

Findings

Data for technical success were available for 5536 of 5611 patients; 75 declined protocol treatment, had no SLNs removed, or had no SLN resection done. SLNs were successfully removed in 97·2% of patients (5379 of 5536) in both groups combined. Identification of a preincision hot spot was associated with greater SLN removal (98·9% [5072 of 5128]). Only 1·4% (189 of 13171) of SLN specimens were outside of axillary levels I and II. 65·1% (8571 of 13 171) of SLN specimens were both radioactive and blue; a small percentage was identified by palpation only (3·9% [515 of 13 171]). The overall accuracy of SLN resection in patients in group 1 was 97·1% (2544 of 2619; 95% CI 96·4–97·7), with a false-negative rate of 9·8% (75 of 766; 95% CI 7·8–12·2). Differences in tumour location, type of biopsy, and number of SLNs removed significantly affected the false-negative rate. Allergic reactions related to blue dye occurred in 0·7% (37 of 5588) of patients with data on toxic effects.

Interpretation

The findings reported here indicate excellent balance in clinical patient characteristics between the two randomised groups and that the success of SLN resection was high. These findings are important because the B-32 trial is the only trial of sufficient size to provide definitive information related to the primary outcome measures of survival and regional control. Removal of more than one SLN and avoidance of excisional biopsy are important variables in reducing the false-negative rate.

Introduction

The sentinel-lymph-node (SLN) concept, based on observations of blue dye injected into tissues, has been noted in published work since at least the 1920s.¹ The modern concept of using the pathological status of the SLN to decide whether regional lymphatic clearance should be done was clearly articulated by Cabanas in 1977.² Development of practical methods of SLN identification in the 1990s resulted in widespread use of the SLN as an indicator for further clearance.3, 4, 5 The application of SLN surgery to patients with breast cancer is a major opportunity for reducing morbidity through individualised lymphatic mapping and reducing the magnitude of lymph-node resection.

Key issues associated with SLN surgery compared with additional axillary lymph-node dissection (ALND) are effects on survival, regional control, morbidity, and accuracy of the procedure. The primary endpoints of the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-32 trial are, therefore, survival, regional control, and morbidity. The number of events for the definitive analyses of these endpoints has not yet been reached and patients are being carefully monitored. Two secondary endpoints, accuracy and technical success, are complete and are reported here as the first available outcomes for this trial. Incidence of allergic reactions is also reported. Data presented here are based on a controlled randomised trial that used a consistent method of surgery and pathological assessment over an extended period of time, to ensure that the primary endpoints, once completed, will be as comparable as possible.