Sex-stratified Integrated Analysis of US lung Cancer Mortality, 1994-2020

ImportanceLung cancer mortality in the United States has fallen substantially in recent decades, yet the relative influence of behavioral, environmental, socioeconomic, and therapeutic factors and their sex specific contributions remains unclear. Understanding these drivers is essential to sustain progress and reduce persistent disparities. ObjectiveTo quantify how behavioral, environmental, socioeconomic, and therapeutic determinants collectively shaped US lung cancer mortality from 1994 to 2020, assess sex specific differences, and forecast mortality trajectories through 2030 using an integrated machine learning framework. Design, Setting, and ParticipantsEcological time series study using publicly available national data from 1994 to 2020. Sex stratified analyses were conducted integrating lung cancer mortality, smoking prevalence, fine particulate matter PM2.5 exposure, Human Development Index HDI, per capita healthcare expenditure, healthcare inflation, insurance coverage, income inequality, and annual drug approvals. ExposuresBehavioral smoking, environmental PM2.5, socioeconomic HDI health expenditure inflation, uninsurance inequality, and therapeutic drug approval indicators. Main Outcomes and MeasuresAge-standardized lung cancer mortality per 100000 population. Temporal changes were modeled using Joinpoint regression. Concurrent associations were assessed using multivariable and elastic net regression, and forecasts were estimated with AutoRegressive Integrated Moving Average models with exogenous variables ARIMAX. ResultsFrom 1994 to 2020, mortality declined by 59 percent in men, from 52.9 to 21.7 per 100000, and by 40 percent in women, from 26.7 to 15.9 per 100000, with faster declines after 2015. Smoking and PM2.5 decreased by more than 45 percent but remained strongly correlated with mortality. In elastic net models, PM2.5 was the strongest predictor for men, while smoking was the strongest predictor for women. Per capita expenditure and HDI ranked higher for men, while uninsurance and income inequality were strong predictors for women. Mortality declines occurred during periods of major approvals of lung cancer drugs. Forecasts suggest continued but slower declines through 2030, with projected rates of 20.2 and 14.9 deaths per 100000 in men and women, respectively. Conclusions and RelevanceSex specific declines in lung cancer mortality reflect different dominant correlates, with air pollution more important in men and smoking more important in women, while socioeconomic conditions and therapeutic advances also influence trends. Continued tobacco control, improved air quality, and equitable access to screening and modern treatment are essential to sustain further reductions in mortality.