ABSTRACT Background Comparisons among treatment strategies for potentially resectable Stage III–N2 driver gene–negative non–small cell lung cancer (NSCLC) remain limited. We evaluated three treatment strategies—neoadjuvant chemoimmunotherapy followed by surgery (NCIT+surgery), NCIT followed by chemoradiotherapy (NCIT+CRT), and definitive concurrent chemoradiotherapy followed by immunotherapy (CRT + IT)—to investigate whether CRT could represent a feasible option to surgery. Methods Patients with Stage III–N2 NSCLC from two institutions (2019–2024) were retrospectively enrolled. Primary endpoints were progression‐free survival (PFS) and overall survival (OS). Subgroup analyses included metastatic N2 lymph node status, stage, programmed death ligand 1 expression, radiographic response to NCIT, and adjuvant or consolidation immunotherapy after surgery or CRT. Baseline differences were balanced 1:1 by propensity score matching (PSM). Survival was estimated by the Kaplan–Meier method and compared via the log‐rank test. Results A total of 363 patients were included: NCIT+Surgery ( n = 176), NCIT+CRT ( n = 55), and CRT + IT ( n = 132). The median follow‐up time was 31.5 months. Before and after PSM, PFS, and OS were longer in NCIT+Surgery than in CRT + IT, whereas no significant difference was observed between NCIT+Surgery and NCIT+CRT. Subgroup analysis showed that survival did not differ significantly between NCIT+Surgery and CRT + IT in patients with multistation or bulky N2 metastasis, whereas CRT + IT was associated with inferior PFS and OS in patients without these features. Conclusions Survival did not differ significantly between CRT and surgery after NCIT, nor between CRT + IT and NCIT + Surgery among patients with multistation or bulky N2 disease. Whether CRT can serve as an alternative to surgery in this population requires validation in large‐scale prospective studies.
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