Abstract
BACKGROUND: Immunotherapy has redefined the treatment era for metastatic non-small cell lung cancer (NSCLC); therefore, this study aimed to explore trends in survival and cardiovascular disease (CVD) mortality risk before and after the widespread adoption of immunotherapy. METHODS: This research utilized information from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute and the Wide-Ranging Online Data for Epidemiologic Research (CDC-WONDER) database from the Centers for Disease Control and Prevention. The study population comprised patients with metastatic NSCLC from the pre- (2011-2014) and post-immunotherapy (2016-2019) periods. Survival determinants and CVD mortality trends were analyzed using propensity score matching, Kaplan-Meier survival analyses, competing risk models, and accelerated failure time (AFT) models. RESULTS: A total of 78,028 metastatic NSCLC patients were enrolled in the study, with significant improvements noted in overall survival (OS) and cancer-specific survival (CSS) in the later stages of immunotherapy. The AFT model analysis identified treatment modality, pathological subtype, metastatic site, and some non-medical factors as survival determinants. The interaction analyses revealed that the survival differences among certain subgroups intensified in the post-immunotherapy period. Despite the lack of significant differences in CVD mortality and subgroup composition between the two periods, CVD mortality risk remained high compared with the general U.S. population. CONCLUSION: Survival of patients with metastatic NSCLC has improved significantly since the introduction of immunotherapy. However, survival differences between some subpopulations continue to intensify, while CVD mortality risk also remains a key concern.