Effects of Sex on Mortality in Patients With Lung Cancer: A Multiple Mediation Analysis of The Boston Lung Cancer Study.

OBJECTIVE

Identify the specific variables that can explain the sex difference in lung cancer mortality.

MATERIAL AND

METHODS

This retrospective cohort study analyzed data from the Boston Lung Cancer Study (1992-2022). We employed descriptive statistics, Wilcoxon rank-sum test, and Pearson's Chi-square test to compare demographic and clinical variables by sex. Kaplan-Meier survival curves and Cox proportional hazards models were used to evaluate survival differences. Mediation analysis was conducted to investigate causal pathways through which sex influences mortality, incorporating cancer stage, smoking status, and treatment modalities.

RESULTS

Among 7642 patients, 53.7% were women. Men were older, had heavier smoking histories, and more frequently received chemotherapy and radiotherapy, whereas women underwent more surgeries. Median survival was significantly longer for women (4.54 vs. 2.59 years), with a 29% reduced hazard of lung cancer-related death (HR: 0.71; 95% CI, 0.66-0.75; P < .0001). Approximately 32% of this survival difference was mediated by early-stage diagnosis, surgical intervention, and smoking history.

CONCLUSION

Women exhibited a survival advantage, of which only about one-third was explained by earlier diagnosis and higher surgical intervention rates. The remaining two-thirds of the mortality difference remains unexplained. Addressing these modifiable factors may reduce sex inequalities in lung cancer outcomes.