Why Women Appear To Have Better Outcomes When Undergoing Screening For Lung Cancer.

Rationale: Randomized controlled trials (RCT) of lung cancer screening (LCS) using computed tomography (CT) documented lung cancer mortality reductions between 7.2%-29.2% compared to chest radiograph (CXR). Women appear to have a greater reduction than men.

Objective: To determine why women appear to have better outcomes from LCS compared to Men.

Methods: Secondary analysis of the National Lung Screening Trial (NLST), a RCT comparing CXR with CT among screen eligible individuals aged 55-74 years. Descriptive statistics and a competing risk proportional hazards model that included an interaction between sex and screening arm were used to examine differences in screening outcomes by sex.

Results: Of 31,530 men and 21,922 women, 648 (2. 1%) and 373 (1.7%) died of lung cancer during the study, respectively. Overall mortality was higher in men: 2771 (8.8%) vs 1198 (5.5%). In an adjusted competing cause of death analysis, the LC mortality subdistribution hazard ratio (sHR) favoring CT was significant in women (sHR=0.74, 95% CI: 0.6, 0.9, p=0.003) but not men (sHR=0.91, 95% CI: 0.78, 1.06, p=0.24). The interaction between screening arm and sex was not significant (p=0.1). COPD and heart disease, more prevalent in men, were independently associated with LC death. LC deaths were consistently greater in the CT arm (vs CXR), for pre-existing COPD and DM in men but not women. Of those with lung cancer, women in the CT arm had 53.7% prevalence of adenocarcinoma (AD) histology, while women in the CXR arm and men in both arms had approximately 36-41% AD prevalence. However, there was no overall difference between sexes in the screening difference for AD lethality.

Conclusion: Women in the NLST had a greater reduction in LC mortality, that while not statistically significant, could be the result of more prevalent comorbid disease in men which contributed to greater all-cause and LC mortality.  .