Mutational Landscape and Treatment Response in Extensive-Stage Small-Cell Lung Cancer: A Single-Center Real-World Analysis

Objectives: Small-cell lung cancer (SCLC) is an aggressive malignancy often diagnosed at the extensive stage (ES-SCLC). While chemoimmunotherapy (CIT) has emerged as a first-line option, SCLC’s “cold” immune profile limits broad efficacy. This study evaluates the real-world clinical efficacy of CIT versus chemotherapy (CT) alone and analyzes the association between gene mutation characteristics and clinical indicators. Methods: We retrospectively analyzed 170 patients with ES-SCLC treated at a single center between January 2020 and January 2024. Patients were categorized by first-line treatment (CIT vs. CT). Subgroup analyses were conducted to evaluate treatment response. Genomic profiling was integrated for a subset of patients to identify associations between mutation signatures and clinicopathological factors. Results: Of the 115 patients (67.6%) who received CIT and 55 (32.4%) who received CT, the CIT group achieved a significantly higher objective response rate (76.5% vs. 56.4%). Median progression-free survival was numerically but not significantly longer in the CIT group (6.0 vs. 5.8 months). Adrenal metastasis was identified as an independent adverse prognostic factor. Genomic analysis revealed site-specific correlations: MYC mutations with pleural metastasis, NTRK3 with brain metastasis, ALK with adrenal metastasis, and NTRK1 with intrapulmonary metastasis. Additionally, smokers showed higher mutation frequencies in SMAD4 and PIK3CA. Conclusions: CIT significantly improves initial response rates in ES-SCLC compared to CT alone. Baseline adrenal metastasis serves as a poor prognostic indicator. Distinct genomic mutation signatures are associated with clinical characteristics, suggesting potential pathways for personalized treatment strategies.