Skip mediastinal metastasis versus pN1 and validation of 9th edition N substaging in lung cancer

Background Skip mediastinal (skip N2) metastasis may be associated with favorable outcomes after resection for non-small cell lung cancer (NSCLC). This study evaluated the prognostic significance of skip N2 metastasis, compared recurrence-free survival with pathological N1 (pN1) disease using propensity score matching, and validated 9th-edition N2 substaging. Methods We analysed 1,118 patients with pathologically confirmed N1–N2 non-small cell lung cancer who underwent complete resection with systematic lymph node dissection between 2003 and 2022 at a single tertiary centre. Patients were classified as pN1 ( n = 622), skip N2 ( n = 151), or non-skip N2 ( n = 345). Propensity score matching with eight covariates compared skip N2 with pN1. The primary endpoint was recurrence-free survival. Results Median follow-up was 44.5 months (interquartile range 24.0–75.8). Skip N2 demonstrated significantly better 5-year recurrence-free survival than non-skip N2 (68.9% vs. 44.7%; adjusted hazard ratio 0.49, 95% confidence interval 0.35–0.70; p < 0.001). After propensity score matching (141 skip N2 and 258 pN1) with excellent covariate balance (all standardized mean differences < 0.1), recurrence-free survival did not differ significantly between the groups (hazard ratio 0.87, 95% confidence interval 0.59–1.29; p = 0.50). The 9th edition N2a/N2b classification showed significant stratification (53.6% vs. 36.3%; p = 0.010). Four-group analysis demonstrated a hierarchical pattern: skip N2a 69.5%, skip N2b 51.9%, non-skip N2a 44.8%, and non-skip N2b 33.3% ( p < 0.001). Competing-risk analyses yielded consistent results. Conclusions Skip N2 metastasis is an independent favourable prognostic factor in resected pN2 NSCLC. After propensity score matching, recurrence-free survival did not differ significantly between skip N2 and pN1 disease, although formal equivalence was not tested. Skip status provided prognostic information beyond station count alone and should be considered in risk stratification for pN2 non-small cell lung cancer.