Survival Determinants and Treatment Outcomes of Patients with Small Cell Lung Cancer and Brain Metastases: A U.S. National Analysis

<b>Background/Objectives</b>: Brain metastases (BM) are common in small cell lung cancer (SCLC) and portend poor outcomes. Contemporary determinants of survival in the modern treatment era remain incompletely defined. We evaluated factors associated with overall survival (OS) among patients with SCLC and BM using a recent, nationally representative dataset. <b>Methods</b>: We identified adults diagnosed with SCLC and brain metastases between 2018 and 2020 in the National Cancer Database (NCDB). Demographic, clinical, treatment, and survival data were extracted for analysis. Unadjusted OS was estimated using Kaplan-Meier methods. Multivariable Cox proportional hazards models identified factors associated with mortality, with proportional hazards (PH) assessed using scaled Schoenfeld residuals. Complementary Accelerated Failure Time (AFT) modeling was performed to confirm robustness. <b>Results</b>: Of 62,671 SCLC cases, 11,074 (17.7%) had BM, including 32.6% with brain-only disease. Median overall survival (mOS) was 6.6 months (95% CI, 6.47-6.87); patients with brain-only disease had an mOS of 8.8 months (8.38-9.26), compared with 5.95 months (5.75-6.18) for those with concurrent extracranial metastases. In multivariable analysis, age ≥ 65 years (HR 1.13, <i>p</i> < 0.001) was associated with higher mortality, whereas female sex (HR 0.87, <i>p</i> < 0.001), Black (HR 0.88, <i>p</i> = 0.001), Asian (HR 0.80, <i>p</i> = 0.022), and Hispanic (HR 0.87, <i>p</i> = 0.008) patients had lower hazards. Worse outcomes were associated with public or no insurance, lower income, non-academic facilities, and extracranial metastases; educational attainment was not significant. Proportional hazards assumptions were largely met with minor deviations, and AFT modeling confirmed consistent results. Treatment modality remained independently associated with survival in both models. <b>Conclusions</b>: In this contemporary national cohort, survival among patients with SCLC and brain metastases was influenced by multiple clinical, sociodemographic, and treatment factors, including age, sex, insurance status, facility type, and extent of metastatic disease. Treatment modality remained an independent predictor of survival. These results provide updated real-world benchmarks and highlight the need for prospective studies to define optimal management strategies in this high-risk population.