Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23–01): a phase 3 randomised controlled trial

Abstract

Background For breast cancer patients with a metastatic sentinel node (SN), axillary dissection (AD) has been standard treatment. However, for patients with minimal SN involvement, AD may be overtreatment. IBCSG Trial 23-01 was designed to determine whether no AD is non-inferior to AD in patients with one or more micrometastatic (≤2 mm) SNs and tumour ≤5 cm. Methods In this multicentre trial patients were randomised to AD or no AD. Eligibility was limited to patients with clinically-palpable axillary lymph node(s) and a primary tumour ≤ 5 cm who, after sentinel node biopsy, had one or more micrometastatic (≤ 2 mm) sentinel lymphs nodes with no extracapsular extension. The primary endpoint was disease-free survival (DFS). Non-inferiority was defined as a hazard ratio of <1·25 for no AD vs. AD. The analysis was intention to treat. Patients were randomly allocated in a 1:1 ratio to AD or no AD with stratification by centre and menopausal status. There was no attempt to blind the treatment assignment. The trial is registered with ClinicalTrials.gov, NCT00072293. Per protocol, disease and survival information continues to be collected yearly. Findings From 2001 to 2010, 934 patients were randomised; 931 were evaluable (464 in the AD group and 467 in the no AD group). After a median follow-up of 5·0 (IQR 3.6–7.3) years, there were 124 DFS events, including breast-cancer-related events in 95 patients (local, 18; contralateral breast, 12; regional, 6; and distant, 59), and other events in 29 (second malignancy, 26; death without prior cancer event, 3). Five-year DFS was 87·8% (95% CI 84·4%–91·2%) in the no AD group and 84·4% (95% CI 80·7%–88·1%) in the AD group (log-rank p=0·16) (HR no AD vs. AD=0·78, 95% CI 0·55–1·11, non-inferiority p=0·0042). Patients with reported long-term surgical events (grade 3–4) included 1 sensory neuropathy (grade 3), 3 lymphedema (2 grade 3 and 1 grade 4), and 3 motor neuropathy (grade 3), all in the AD group, and 1 grade 3 motor neuropathy in the no AD group. One serious adverse event was reported, a post-operative infection in the axilla in the AD group. Interpretation AD in patients with early breast cancer represented in this study (most had tumours < 3 cm (92%; 856/931), received breast conserving surgery (91%; 845/931) and adjuvant systemic therapy (96%; 892/931)) should be avoided when the SN is minimally involved, thus eliminating complications of axillary surgery with no adverse effect on survival. Funding Supported in part: local participating centres, IBCSG central funds, CA075362 from the U.S. National Cancer Institute, and Swiss Cancer League/Cancer Research- Switzerland/Oncosuisse (ICPOCS 01688-03-2005). No pharmaceutical company funds were used.

Sensitivity and Specificity of Pre-Operative Staging of the Axilla When Using OSNA in Breast Cancer Patients

“…The omission of further surgery for these patients is thus warranted given that there has now been a strong move away from clearing for micro metastases identified by standard techniques. The sensitivities reported here for the detection of both micro and macro-metastases (23% to 29%) are at the lower end of those previously published [14] [15]. This may reflect the fact that the dataset includes micro-metastases within the positive node group.…”

Are the Conclusions of Z11 Relevant to Community Practice?

“…It is unclear whether these patients may have derived less benefit from an ALND, masking the benefit of ALND in patients with a greater burden of nodal disease. The recently published IBCSG 23-01 trial, looking specifically at patients with micrometastatic disease in their sentinel lymph nodes, lends support to this theory 11 . This study concluded that axillary dissection could be avoided in patients with early stage breast cancer and limited sentinel-node involvement without an adverse effect on survival.…”

Controversial issues in the management of older adults with early breast cancer

“…as the "standard of care" in clinically node negative (cN0) disease and no further treatment of the axilla is advised in cases of a negative SLN, or when it contains isolated tumour cells or a micro-metastasis as there is no benefit in terms of disease free survival (DFS) or overall survival (OS) [5].…”