Sex and Survival After Surgery for Lung Cancer: A Swedish Nationwide Cohort

Abstract

Background: Prior reports on a possible female survival advantage in both surgical and nonsurgical cohorts of patients with lung cancer are conflicting. Previously reported differences in survival after lung cancer surgery could be the result of insufficient control for disparities in risk factor profiles in men and women.

Research question: Do women who undergo pulmonary resections for lung cancer have a better prognosis than men when taking a wide range of prognostic factors into account?

Study design and methods: We performed a nationwide population-based observational cohort study analyzing sex-specific survival after pulmonary resections for lung cancer. We identified 6356 patients from the Swedish National Quality Register for General Thoracic Surgery and performed individual-level record linkage to other national health-data registers to acquire detailed information regarding comorbidity, socioeconomic status, and vital status. Inverse probability of treatment weighting was used to account for differences in baseline characteristics. The association between female sex and all-cause mortality was assessed with Cox regression models, and flexible parametric survival models were used to estimate the absolute survival differences with 95% CIs. We also estimated the difference in restricted mean survival time.

Results: We observed a lower risk of death in women compared with men (hazard ratio, 0.73; 95% CI, 0.67-0.79). The absolute survival difference at 1, 5, and 10 years was 3.0% (95% CI, 2.2%-3.8%), 10% (95% CI, 7.0%-12%), and 12% (95% CI, 8.5%-15%), respectively. The restricted mean survival time difference at 10 years was 0.84 year (95% CI, 0.61-1.07 years). The findings were consistent across several subgroups.

Interpretation: Women who underwent pulmonary resections for lung cancer had a significantly better prognosis than men. The survival advantage was evident regardless of age, common comorbidities, socioeconomic status, lifestyle factors, physical performance, type and extent of surgery, tumor characteristics, and stage of disease.

Trial registry: ClinicalTrials.gov; No.: NCT03567538; URL: www.clinicaltrials.gov.

Keywords: epidemiology (pulmonary); lung cancer; sex; thoracic surgery.

Figure 1

Kaplan-Meier estimated survival curve plotted against time from surgery and stratified according to sex. Male patients are the reference group. The numbers of patients at risk are not necessarily integers owing to inverse probability of treatment weighting. HR = hazard ratio.

Figure 2

A, Bar graph showing survival at 5 years in age categories according to sex. B, Hazard ratios and 95% CIs for the association between female sex and all-cause mortality in the unweighted (red) and weighted (blue) population in different age categories. Male patients are the reference group. IPTW = inverse probability of treatment weighting.

Figure 3

Kaplan-Meier estimated survival curves plotted against time from surgery and stratified according to sex in different subsets of patients. A, Adenocarcinoma. B, Squamous cell carcinoma. C, Stage IA and IB disease. D, Stage IIA and IIB disease. The numbers of patients at risk are not necessarily integers owing to inverse probability of treatment weighting. HR = hazard ratio.