PurposeThis study aimed to investigate the prognostic significance of surgery in large-cell neuroendocrine carcinoma (LCNC) patients.MethodsA total of 453 patients from the Surveillance, Epidemiology, and End Results database diagnosed with stage T1-4N0-2M0 LCNC from 2010 to 2015 were analyzed. The propensity-score matching analysis with a ratio of 1:1 was used to minimize the bias effect of other clinical characteristics, and 77 pairs of patients’ data were performed for subsequent statistical analysis. The Cox proportional hazards model, Kaplan-Meier analysis, and Log-rank test were used in the present study. The primary observational endpoint was cancer-specific survival (CSS).ResultsThe 1-year, 3-year, and 5-year CSS rates were 60.0%, 45.0%, and 42.0% in those 453 LCNC patients. Compared with patients who underwent surgical resection, patients without surgery had a lower 5-year CSS rate (18.0% vs. 52.0%,P< 0.001). After analyses of multivariable Cox regression, chemotherapy, T stage, N stage, and surgery were identified as independent prognostic indicators (allP< 0.05). In the cohort of old patients, the median survival time was longer in cases after surgery than those without surgery (13.0 months vs. NA,P< 0.001). Besides, in patients with different clinical characteristics, the receiving surgery was a protective prognostic factor (all hazard ratio < 1, allP< 0.05). In addition, for the cohort with stage T1-2N0-2M0, patients after the operation had more improved outcomes than patients without surgery (P< 0.001).ConclusionsWe proposed that the surgery could improve the survival outcomes of LCNC patients with stage T1-4N0-2M0. Moreover, old patients could benefit from surgery.