Prognostic significance of nodal subclassification and adjuvant therapy in surgically treated T1-4N1-2M0 non-small cell lung cancer: a single-center retrospective study

BACKGROUND: This study evaluated the prognostic significance of nodal subclassification in surgically treated patients with non-small cell lung cancer who had pathological N1-N2 disease, based on the ninth edition of the Tumor-Node-Metastasis classification. METHODS: All patients with pathologically confirmed stage T1-4N1-2M0 non-small cell lung cancer who underwent anatomical lung resection with systematic mediastinal lymph node dissection were retrospectively reviewed. Patients who received preoperative therapy or had incomplete resections were excluded. Nodal involvement was classified as pathological N1, N2a, and N2b; N2 cases were divided into N2a1, N2a2, N2b1, and N2b2 according to skip and station status. In addition, single-zone and multi-zone metastases were evaluated to investigate the spatial distribution of mediastinal spread. Overall and recurrence-free survival were analyzed using Kaplan-Meier and multivariable Cox regression methods. RESULTS: The median overall survival was 45, 30, and 19 months for the pathological N1, N2a, and N2b groups, respectively. Patients in the N2a2 subgroup demonstrated the most favorable survival, whereas those in the N2b2 subgroup had the poorest outcomes. Skip metastasis was not associated with any survival benefit, while multi-station and multi-zone involvement were related to worse long-term results. In multivariable analysis, multiple-station disease and postoperative complications were independent adverse factors, whereas younger age and administration of adjuvant chemotherapy were independently associated with improved survival. CONCLUSION: The ninth edition of the Tumor-Node-Metastasis classification provides a more accurate prognostic stratification for surgically treated patients with pathological N2 disease. Multi-station and multi-zone metastases represent more aggressive patterns, while carefully selected single-station N2a2 cases can achieve survival similar to N1 disease, supporting the clinical usefulness of refined nodal and zone-based subclassification.