Sex-associated differences in non-small cell lung cancer in the new era: is gender an independent prognostic factor?

Background: Women with non-small cell lung cancer (NSCLC) appear to have better survival. This study aimed to evaluate sex differences in NSCLC in recent years. The true effect of gender on the overall survival was analyzed taking other prognostic factors into account.
Methods: A cohort of consecutive NSCLC patients was prospectively enrolled from January 2002 to December 2005, and followed-up until December 2006. They were clinically and pathologically staged and underwent homogenous treatment algorithms. Demographics, histology, and disease stage between sexes were compared. The clinical prognostic factors to be analyzed in addition to gender included stage, age, smoking history and histology. The overall survival of females and males within relevant subgroups defined by smoking history and histology was also compared.
Results: Of the 738 patients, 695 were analyzed with a definite stage (94.2%; 315 females and 380 males), which was similar in both sexes. Females were younger (median age: 59.5 years vs. 65.0 years; P<0.001) and more likely to have adenocarcinoma (81% vs. 60.5%; P<0.001). Patients with earlier stage, younger patients, never-smokers and females had better overall survival in univariate analyses and no significant survival difference was noted between adenocarcinoma and squamous cell carcinoma. Multivariate analyses demonstrated age, smoking history and gender to have a hazard ratio 1.46 (95% confidence interval, CI 1.21-1.76; P<0.001), 1.27 (95% CI 0.97-1.65; P=0.082), and 1.18 (95% CI 0.90-1.55; P=0.226), respectively. Subgroup analyses revealed the survival of never-smoker males with adenocarcinoma was similar to that of females.
Conclusions: There are sex-related differences in the clinico-pathologic characteristics and survival of NSCLC patients. The survival advantages of females could be attributed to the younger age and lower smoking prevalence. Never-smokers with adenocarcinoma should be given special attention regardless of sex as they imply better survival with different treatment outcomes.