Evaluating Prognostic Factors for Sex Differences in Lung Cancer Survival: Findings From a Large Australian Cohort

Women tend to survive a lung cancer diagnosis longer than men; however potential drivers of this sex-related disparity remain largely elusive. We quantified factors related to sex differences in lung cancer survival in a large prospective cohort in Australia. Participants in the 45 and Up Study (recruited 2006–2009) diagnosed with incident lung cancer were followed up to December 2015. Prognostic factors were identified from questionnaire data linked with cancer registrations, hospital inpatient records, emergency department records, and reimbursement records for government-subsidized medical services and prescription medicines. Hazard ratios (HRs) and 95% confidence intervals (CIs) for lung cancer death for men versus women were estimated using Cox proportional hazard regression in relation to key prognostic factors alone and jointly. A total of 488 women and 642 men were diagnosed with having lung cancer. Women survived significantly longer (median 1.28 versus 0.77 y; HR for men = 1.43, 95% CI: 1.25–1.64, p < 0.0001). The survival disparity remained when each subgroup of major prognostic factors was evaluated separately, including histologic subtype, stage at diagnosis, treatment received, and smoking status. Multivariable analyses revealed that treatment-related factors explained half of the survival difference, followed by lifestyle and tumor characteristics (explaining 28%, 26%, respectively). After adjusting for all major known prognostic factors, the excess risk for men was reduced by more than 80% (HR = 1.06, 95% CI: 0.96–1.18, p = 0.26). The sex-related lung cancer survival disparity in this Australian cohort was largely accounted for by known prognostic factors, indicating an opportunity to explore sex differences in treatment preferences, options, and access.