Sex-Dependent Staging in Non–Small-Cell Lung Cancer; Analysis of the Effect of Sex Differences in the Eighth Edition of the Tumor, Node, Metastases Staging System

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Abstract

Because men with lung cancer have poorer survival, we examined the effect of sex on the prognostic value of the eighth edition of tumor, node, metastases staging (TNM). Men had worse 5-year survival within each stage. This suggests that outcomes in TNM staging should be quoted separately for men and women to improve the prognostic, research, and clinical accuracy.

Introduction:

Non–small-cell lung cancer (NSCLC) has disproportionately negative outcomes in men compared with women. The importance of the relationship between sex and tumor, node, metastases (TNM) staging system remains unknown. The objective of this study was to investigate the effect of sex on NSCLC survival for each stage in the eighth edition of the TNM staging system in NSCLC.

Patients and Methods:

Two cohorts treated surgically with curative intent between 2000 and 2010 were analyzed. The primary cohort was from Australia with a second population set from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate analyses of putative and validated prognostic factors were undertaken to investigate sex-dependent prognostication with detailed analyses of sex differences in each TNM stage. The primary outcome was disease-specific survival (DSS) at 5 years.

Results:

Inclusion criteria were met by 555 patients in the Australian cohort, 335 men (60.4%) and 220 (39.6%) women; and 47,706 patients from the SEER cohort, 24,671 men (51.7%) and 23,035 women (48.3%). Five-year DSS was significantly worse for men in multivariate analyses for the Australian (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.04-1.98; P = .026) and SEER (HR, 1.24; 95% CI, 1.20-1.28; P < .001) cohorts. Detailed analysis of TNM stage sex differences revealed a consistent pattern of men having worse survival than women across stages in both cohorts.

Conclusion:

The poorer survival in men with NSCLC presents research and clinical communities with an important challenge. This study's findings suggest that for men and women diagnosed with NSCLC, and managed surgically, stage-specific outcomes should be quoted separately and consideration to a rapid prognostic score with sex combined with staging as a key element.

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