Trends in cause of death among patients with non-small cell lung cancer in the United States from 2000 to 2021: a SEER-based study

The diagnosis and treatment of non-small cell lung cancer (NSCLC) has made rapid progress. Cancer survivors with prolonged survival time are also susceptible to non-cancer diseases. The study aims to identify the causes of death in NSCLC for improved management and survival. Data were extracted from National Cancer Institute’s Surveillance, Epidemiology, and End Results program (2000–2021). Cumulative incidence of mortality in NSCLC patients, considering both lung cancer-related and other causes, were calculated using the competing-risks regression model. The trend in annual age-standardized mortality rate from various causes of death in NSCLC was described by the joinpoint regression model. The distributions of the leading 10 non-cancer causes of death in NSCLC were reported via stacked area charts and bar charts. Moreover, subgroup analyses based on tumor stage, age, and pathological type were conducted. Among all 768,309 patients with NSCLC, mortality from lung cancer accounted for approximately 76.4% deaths (479,520/627,976). However, the proportion of deaths attributable to lung cancer gradually decreased over time, although it remained the predominant cause of death. The cumulative incidence of mortality from lung cancer ranged from 52% to 69% from 24 to 144 months after diagnosis, while that of mortality from other causes ranged from 12% to 27%. Moreover, there was a larger-magnitude decrease in the annual mortality from lung cancer than other causes (average annual percent change [AAPC] − 4.38% (− 5.65 to − 3.00%) vs. − 2.43% (− 3.69 to − 0.93%)), and the proportion of deaths from other causes increased from 16.18% to 35.34%. The change was particularly evident among the elderly (AAPC-lung cancer: −5.21% (− 5.72 to − 4.75%); AAPC-other causes: 0.60% (0.14 to 1.01%)) and those in stage I and in situ (AAPC-lung cancer: −8.42% (− 10.14 to − 6.54%); AAPC-other causes: 3.93% (0.60 to 10.57%)). Diseases of heart, chronic obstructive pulmonary disease and various infections were relatively more prevalent in non-cancer deaths. NSCLC is a complex disease with multiple factors involved, and the therapeutic alternatives have significantly increased. While lung cancer-related death remains the primary cause, the proportion of non-lung cancer-related death has increased, which requires attention.