Clinicopathologic Disease Characteristics and Their Association with Adjuvant Chemotherapy Outcomes in Pulmonary Large-Cell Carcinoma Patients with or Without Neuroendocrine Features

<b>Background:</b> Large-cell carcinoma (LCC) and large-cell neuroendocrine carcinoma (LCNEC) are kinds of rare lung tumors classified as distinct forms of non-small-cell lung cancer (NSCLC). They both differ in cellular morphology, neuroendocrine marker expression, and clinical outcomes. Thus, LCC and LCNEC exhibit different clinicopathological characteristics and survival outcomes. This study seeks to assess how clinicopathological and immunohistochemical features influence the need for adjuvant chemotherapy in individuals with early-stage, surgically resected LCC or LCNEC. <b>Methods:</b> This multicenter retrospective analysis included 79 patients who underwent surgical resection for large-cell carcinoma (LCC) or large-cell neuroendocrine carcinoma (LCNEC) between January 2008 and March 2025. We evaluated prognostic factors that influence survival in patients with LCC and LCNEC and assessed the effect of adjuvant chemotherapy on survival outcomes. <b>Results:</b> This study included 79 patients-39 diagnosed with LCC and 40 diagnosed with LCNEC. All patients were in stages I-III and received curative surgery. The median age was 61 years for LCC patients and 58.5 years for LCNEC patients. The median overall survival (mOS) was 80.1 months for patients with LCC and 34.2 months for those with LCNEC. Multivariate Cox regression analysis revealed that age (HR: 0.279), stage (HR: 0.198), and chromogranin A expression (HR: 0.088) were independent prognostic factors for overall survival in LCC patients. In LCNEC patients, stage (HR: 0.20), synaptophysin expression (HR: 0.30), type of surgery (HR: 0.31), and adjuvant chemotherapy (HR: 0.264) were identified as factors influencing overall survival. Adjuvant chemotherapy improved overall survival in LCNEC patients (67.0 vs. 17.8 months). <b>Conclusions</b>: Patients with LCNEC generally have poorer prognoses than those with LCC, exhibiting reduced overall survival periods. Disease stage is the most significant factor influencing overall survival for both groups. Notably, in LCNEC patients, adjuvant chemotherapy was found to independently improve survival outcomes regardless of stage.