NAUTILUS RCT reports 11.2% ALN metastasis rate in SLNB arm for cT1-2/N0 breast cancer

The NAUTILUS trial is a randomized controlled trial investigating the omission of sentinel lymph node biopsy (SLNB) versus standard SLNB in patients with clinically node-negative, early-stage breast cancer. This report presents baseline clinicopathologic characteristics and axillary lymph node status from the trial, though it does not yet report the comparative outcomes of the intervention versus comparator. The study phase, specific setting, and follow-up duration are not reported in this preliminary analysis.

The intervention studied was the omission of sentinel lymph node biopsy (SLNB), while the comparator was the standard performance of SLNB. The trial enrolled patients with cT1-2/N0 breast cancer, with specific dosing or procedural protocols for the SLNB not detailed in this report. The population consisted of 1,734 randomized patients, with 1,664 subjects available for the baseline characteristics analysis presented here. The median age was 55 years (range 29-92), with 40.1% of patients being premenopausal. Pathologic tumor staging showed 1.7% pTmic, 83.9% pT1, and 14.0% pT2 disease, with a median tumor size of 1.3 cm (range 0.1-6.0 cm).

This report does not present primary outcome results, as the comparative efficacy data for SLNB omission versus SLNB are not yet reported. The key finding presented is the axillary lymph node (ALN) metastasis rate within the SLNB arm of the trial. Among patients who underwent SLNB, 11.2% were found to have ALN metastasis. This breakdown included 1.1% with pN1mic disease, 9.4% with pN1 disease, and 0.6% with pN2-3 disease. No p-values, confidence intervals, or comparative effect sizes between the intervention and comparator arms are provided, as this is a baseline report.

A key secondary analysis presented the ALN metastasis rate stratified by tumor size within the SLNB arm. For tumors ≤1.0 cm, the metastasis rate was 7.0%. For tumors >1.0 cm and ≤2.0 cm, the rate was 12.8%. For tumors >2.0 cm and ≤5.0 cm, the rate increased to 17.2%. These data illustrate the relationship between increasing tumor size and higher likelihood of nodal involvement in this clinically node-negative population.

Safety and tolerability findings are not reported in this analysis. The report does not include data on adverse events, serious adverse events, discontinuations, or tolerability profiles associated with either the SLNB procedure or its omission. The absence of this comparative safety data is a significant gap in the current report, as the potential risks and benefits of omitting a diagnostic surgical procedure are central to the trial's clinical question.

These baseline results from NAUTILUS contribute to the growing evidence base examining de-escalation of axillary surgery in early breast cancer. Prior landmark trials in this area include SOUND and INSEMA, which have investigated similar questions regarding the safety of omitting SLNB in selected patients. The authors suggest expectations that NAUTILUS will show the impact of SLNB omission in subgroups including those with pT2 disease (14.0% of this cohort) and premenopausal patients (40.1% of this cohort), but these are projections rather than reported findings from this trial.

Key methodological limitations of this report include its preliminary nature, as it presents only baseline characteristics without the comparative outcomes that constitute the trial's primary objective. The follow-up duration is not stated, leaving uncertainty about the maturity of the eventual outcome data. The report does not detail randomization methods, blinding, or statistical power calculations. Funding sources and author conflicts of interest are also not reported, which limits assessment of potential biases.

The clinical implications of this report are currently limited to understanding the baseline characteristics and nodal involvement rates in a contemporary cohort of patients eligible for trials of axillary de-escalation. For practice decisions, clinicians should note that in this trial's SLNB arm, 11.2% of patients with clinically node-negative, cT1-2 breast cancer had pathologic nodal involvement, with rates varying substantially by tumor size. However, the critical question of whether omitting SLNB in similar patients leads to equivalent oncologic outcomes remains unanswered by this report.

Several important questions remain unanswered. The comparative efficacy of SLNB omission versus SLNB on recurrence-free survival, overall survival, and regional control is not yet reported. The safety profile and patient-reported outcomes associated with omitting the procedure are unknown. The optimal selection criteria for patients who might safely forego SLNB require clarification, particularly for those with larger tumors (pT2, 14.0% of this cohort) or premenopausal status (40.1% of this cohort). Long-term follow-up data are needed to assess the durability of any non-inferiority that may be demonstrated in future reports.