Beneficial outcomes of surgical combination therapy for patients with N3M0 non - small cell lung cancer: a retrospective cohort study

Background: The optimal role of surgery in N3M0 non-small cell lung cancer (NSCLC) remains controversial. This study aimed to evaluate whether surgical resection provides survival benefit in the context of modern multimodal treatment strategies. Patients and Methods: Patients with pathologically confirmed NSCLC staged as N3M0 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and cancer-specific survival (CSS) were assessed using Kaplan–Meier analysis, Cox proportional hazards models, and competing risk models. Propensity score matching (PSM) was employed to minimize confounding. Subgroup analyses were conducted across clinical and pathological variables. Results: Multimodal treatment, particularly surgery combined with chemoradiotherapy, achieved the best survival outcomes (OS: 22 months; CSS: 25 months), significantly outperforming monotherapy approaches. Surgery remained an independent predictor of improved OS after multivariable adjustment (HR = 0.74, 95% CI: 0.69–0.80; P < 0.001), and this association persisted in propensity score–matched cohorts. Notably, patients who were recommended for surgery but did not undergo the procedure had significantly worse survival than those who received surgery, suggesting that the survival benefit of surgery is not solely attributable to selection bias. The extent of surgical resection also affected outcomes, with combined resection of the primary tumor and regional lymph nodes yielding the most favorable OS (27 months; HR = 0.50). Among systemic treatment strategies, perioperative therapy was associated with the longest median OS (32 months), exceeding both neoadjuvant (22 months) and adjuvant (16 months) approaches (P < 0.0001). Subgroup analyses demonstrated consistent survival benefits from surgery across various demographic and clinical subpopulations, including those traditionally considered high-risk. After propensity score matching, treatment efficacy varied by tumor biology, with patients with T3–T4 squamous cell carcinoma deriving the greatest survival advantage from surgery. Conclusions: Surgery offers a significant survival benefit in selected patients with N3M0 NSCLC, especially when combined with multimodal treatment. Patients with squamous histology and those receiving perioperative systemic therapy appear to benefit most. These findings support individualized surgical consideration in this traditionally inoperable population.