Skip N2 Metastasis in Resected Lung Cancer: Prognostic Subclassification by Lymphatic Drainage and Histology.

PURPOSE: Skip N2 metastasis in non-small-cell lung cancer (NSCLC) confers a favorable prognosis, yet the biological determinants remain poorly defined. We investigated lymphatic drainage patterns and histological characteristics to develop a novel pN2 subclassification. METHODS: We retrospectively analyzed 180 consecutive pN2 patients (2015-2022); 50 exhibited skip metastasis. Lymphatic drainage was classified as direct, indirect, or mixed, and a composite score incorporating drainage, histology, grade, and lymphovascular invasion stratified patients into 3 risk groups. Survival was assessed with Kaplan-Meier and Cox models. RESULTS: Skip metastasis was associated with superior KM-estimated 5-year overall survival compared to non-skip disease (56% vs 41%; median follow-up 43 months, with 34% of patients reaching the 5-year assessment). Direct drainage predominated in peripheral upper-lobe tumors and correlated with lower lymphovascular invasion. The model distinguished 3 prognostic groups: low-risk (5-year survival 71%), intermediate-risk (55%), and high-risk (27%). The subclassification was an independent prognostic factor, with high-risk patients showing an adjusted hazard ratio of 2.45 (95% CI 1.42-4.23). CONCLUSION: Integrating lymphatic drainage and histology refines prognosis in pN2 lung cancer and provides a hypothesis-generating framework for prognostic stratification of skip N2 disease, with potential to inform future clinical trial design pending validation.