The optimal treatment strategy for resected stage I large cell neuroendocrine carcinoma of the lung (LCNEC) remains unknown. In this analysis, we evaluate the impact of systemic chemotherapy on patients with stage I LCNEC who have undergone surgical resection.

The study population included patients who underwent surgical resection for LCNEC and had pathologic stage I disease. We compared overall survival between patients who underwent surgical resection alone and those who underwent surgical resection plus chemotherapy. Overall survival was estimated by the Kaplan-Meier method, and comparisons were analyzed by using multivariable Cox models and propensity score-matched analyses.

From 2004 to 2013, 1232 patients underwent surgical resection for stage I LCNEC in the National Cancer Database, including 957 patients (77.7%) who underwent surgical resection alone and 275 (22.3%) who received both surgery and systemic chemotherapy. Five-year survival was significantly improved in patients who received chemotherapy (64.5% versus 48.4% [hazard ratio =0.54, 95% confidence interval: 0.43-0.68, p < 0.001]). Multivariable Cox modeling confirmed the survival benefit from chemotherapy for patients with resected stage I LCNEC (hazard ratio = 0.54, 95% confidence interval: 0.43-0.68, p <0.0001). The survival benefit was further confirmed by propensity-matched analysis. In addition, older (age >70 years), comorbid white patients who underwent sublobar resections for tumors larger than 20 mm had worse survival outcomes.

In this largest-reported retrospective study of patients with resected stage I LCNEC, survival was improved in patients who received chemotherapy in both stage IA and stage IB LCNEC.