Anatomical location of metastatic sentinel lymph node and clinicopathological characteristics for predicting risk of non-sentinel lymph node metastasis.

background30 to 70% of patients with positive sentinel lymph nodes (SLNs) in early breast cancer do not develop non-SLN metastases. They are exposed to the potential complications and sequelae of axillary lymph node dissection (ALND) without gaining additional therapeutic benefit. Therefore, a prediction model for non-SLN metastasis is needed. We identified the anatomical location of metastatic SLNs as a key factor for predicting non-SLN status.

methodsWe retrospectively identified 1,717 consecutive patients who underwent SLN biopsy; 481 SLN-positive patients treated from 2009 to 2019 underwent completion ALND and formed the development cohort, and 113 SLN-positive patients treated from 2020 to 2022 served as a temporal validation cohort. A multivariable logistic regression model was developed and presented as a nomogram. Performance was assessed by discrimination and calibration, and clinical utility by decision curve analysis. The Memorial Sloan Kettering Cancer Center (MSKCC) and Shanghai Cancer Hospital (SCH) models were evaluated for comparison.

resultsMultivariate analysis revealed eight independent predictors of non-SLN metastasis: metastatic SLN location, tumor size, multifocality, lymphovascular invasion, extracapsular extension, number of positive and negative SLNs, and size of SLN metastasis. The nomogram based on these variables achieved high discrimination in both the training (AUC = 0.830) and validation (AUC = 0.785) cohorts. In the temporal validation cohort, discrimination was higher than the MSKCC model (AUC= 0.690; P = 0.033) and numerically higher than the SCH model (AUC = 0.716; P = 0.088). At prespecified false-negative rate targets, the model identified 0.9%, 23.0%, and 27.4% of patients as candidates for omitting completion ALND under FNR thresholds of 0%, <5%, and <10%, respectively, and yielded a higher net benefit than the comparator models across clinically relevant risk thresholds. The model also maintained performance in patients with ≥3 positive SLNs (AUC = 0.843).

conclusionsMetastatic SLN location relative to the ICBN is a novel anatomical predictor of non-SLN metastasis. A nomogram incorporating this variable demonstrated good discrimination and clinical utility in a single-center cohort with temporal validation; prospective multicenter validation with standardized ICBN assessment is warranted before broader implementation.