Neoadjuvant chemotherapy with surgery versus concurrent chemoradiation in N2 non-small cell lung cancer: a retrospective comparative analysis of treatment outcomes

Aim: The most effective management approach for non–small cell lung cancer (NSCLC) patients presenting with mediastinal (N2) lymph node involvement has not yet been clearly established. This study compared clinical outcomes between neoadjuvant chemotherapy followed by surgical resection (NACTx-Surgery) and definitive concurrent chemoradiation (CRT) in patients with N2 disease.Methods: In this retrospective cohort analysis, we evaluated 61 individuals diagnosed with N2 stage NSCLC who received treatment at two high level tertiary care institutions. Thirty one patients received NACTx-surgery, and 30 patients received definitive CRT. Overall survival (OS), event free survival (EFS), and prognostic factors were compared using Kaplan-Meier analysis and Cox proportional hazards modeling.Results: The NACTx-surgery group achieved significantly superior median OS (37.9 months vs. 26.8 months; p=0.031) compared with the CRT group. EFS showed a trend toward improvement with NACTx-surgery (median 21.4 months vs. 13.9 months; p=0.052). TNM stage emerged as an independent predictor of EFS in multivariable analysis (HR 0.48; p=0.03). Recurrence occurred in 54.8% of NACTx-surgery patients and 70.0% of CRT patients.Conclusions: For appropriately selected patients with resectable N2 NSCLC, multimodal NACTx-surgery approaches achieved superior survival outcomes compared with definitive CRT. These findings support aggressive pursuit of resectability assessment and multimodal therapeutic planning. Future prospective randomized trials comparing contemporary NACTx-surgery with modern CRT plus consolidation immunotherapy are needed.