Refining N1 classification: prognostic validation of N1 subdivision in resected non-small cell lung cancer

Accurate evaluation of nodal metastasis is essential for staging and prognostication of non-small cell lung cancer (NSCLC). The 9th edition of the TNM classification subdivided N2 into single station(N2a) and multi-station(N2b) involvement, however, pathological N1 disease remains a unified category. This study aimed to evaluate whether subdivision of N1 into N1a and N1b provides meaningful prognostic discrimination.

Patients who underwent surgery for NSCLC between 2005 and 2022 at the Asan Medical Center were retrospectively analyzed. Patients were categorized into N1a (n = 811), N1b (n = 215), N2a (n = 797), and N2b (n = 507). Overall survival (OS) and Recurrence-free survival (RFS) were compared using Kaplan-Meier estimates and multivariable Cox models. Prognostic performance of the 9th TNM model (N1, N2a, N2b) was evaluated against a proposed model incorporating N1 subdivision using Akaike information criterion (AIC), R2, and Harrell's C-index.

A total of 11,047 patients (1,026 with pN1 and 1,304 with pN2) were included. Adjuvant therapy use, extracapsular extension, and extent of nodal involvement increased with advancing N stage. Subdividing N1 showed clear prognostic separation: 5-year OS was 66.2% for N1a vs 53.0% for N1b, and 5-year RFS was 49.6% vs 29.9%, respectively. In multivariable analysis, N1b independently increased mortality risk (HR 1.56 vs N1a), and its outcomes were comparable to N2a. Model incorporating N1 subdivision showed improved prognostic performance, with lower AIC, slightly higher corrected R², and a modestly higher C-index.

Subdividing N1 into single- and multi-station provides meaningful prognostic discrimination in resected NSCLC and provides complementary prognostic information beyond the current TNM staging.