Abstract
BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) accounts for approximately 3% of lung cancers and carries a poor prognosis. For early-stage, node-negative disease classified as T1-2N0M0 by the 9(th) edition tumor, node, metastasis (TNM) staging system, the role of adjuvant chemotherapy following surgical resection remains controversial due to limited evidence from randomized trials. Our research aims to evaluate the effectiveness of adjuvant chemotherapy in this specific patient population using a large national database. METHODS: We sourced data of patients who were diagnosed with LCNEC at the T1-2N0M0 stage and had undergone surgery, focusing on the time frame from the start of 2004 to the end of 2015, using the Surveillance, Epidemiology, and End Results (SEER) database as our resource. In order to comprehensively evaluate the cancer-specific survival (CSS) and overall survival (OS) across different groups, we implemented a multi-faceted statistical approach, encompassing subgroup analyses, propensity score matching (PSM) techniques, and Kaplan-Meier (K-M) survival curves. Additionally, we employed the Cox Proportional-Hazards model to pinpoint standalone predictors of outcomes in LCNEC staged as T1-2N0M0. RESULTS: Of the 582 T1-2N0M0 LCNEC patients studied, 473 (81%) patients underwent surgery alone. Before and after applying propensity score adjustments, we found no notable variance in OS and CSS when comparing the surgery-only cohort to the group that received adjuvant chemotherapy. Exploratory subgroup analyses suggested potential heterogeneity in treatment associations, though biological plausibility was uncertain. Cox regression identified middle tumor location, segmentectomy, age ≥65 years, and zero regional nodes examined as independent prognostic factors (P<0.05). CONCLUSIONS: According to the 9(th) edition of the American Joint Committee on Cancer (AJCC) staging system, adjuvant chemotherapy does not provide significant survival benefits for the overall T1-2N0M0 LCNEC population. Exploratory subgroup analyses suggested potential heterogeneity in treatment associations; however, given the retrospective design and inherent limitations of SEER data (lacking performance status, comorbidities, recurrence data, and detailed chemotherapy information), these hypothesis-generating findings require prospective validation before informing clinical practice.