Gender disparities in metastatic colorectal cancer survival

Abstract

Purpose: Previous studies have shown that estrogen prevents colon cancer in postmenopausal women, indicating a role in colorectal cancer carcinogenesis and tumor progression. We investigated the interactions between sex, age, ethnicity, and year of diagnosis on overall survival (OS) in patients with metastatic colorectal cancer (MCRC).

Experimental design: We screened 52,882 patients with MCRC from 1988 to 2004, using the Surveillance Epidemiology and End Results registry. Age at diagnosis, sex, ethnicity, tumor location, year of diagnosis, OS, and cancer-specific survival were evaluated using Cox proportional hazards model. The models were adjusted for marital status, tumor site, tumor differentiation, and treatment with radiation and/or surgery.

Results: We observed that younger women (18-44 years old) with MCRC lived longer than younger men (17 months versus 14; P < 0.0001, log-rank test). In contrast, older women (55 years and older) had significantly worse OS than older men (7 months versus 9; P < 0.0001, log-rank test). In multivariate analysis, we found that gender discrepancies have widened in recent years; young women diagnosed after 2000 have improved cancer-specific survival, compared to men (hazard ratio, 0.778; 95% confidence interval, 0.669-0.904), but those diagnosed before 2000 benefit less (hazard ratio, 0.931; 95% confidence interval, 0.821-1.056).

Conclusion: As one of the largest data sets analyzed to establish that younger women with MCRC survive longer than younger men, hormonal status not only seems to play an important role in the development and pathogenesis of colorectal cancer but also may be of prognostic significance. These data warrant further studies to determine the role of estrogen in colorectal cancer.

Figure 1. Kaplan-Meier curves of OS in MCRC

Stratified by sex (A), age (B), and ethnicity (C). Log-rank tests were used to calculate significance.

Figure 2. Kaplan Meier curves of OS by sex and year of diagnosis

A - young MCRC patients (≤44 years) B - young patients by year of diagnosis C - old MCRC patients (> 55 years) D - old patients by year of diagnosis

Figure 3. Hazard Ratio (females/males) of cancer specific survival comparing females with males across age all groupings (top panel)

The bottom panel is a sub- group analysis by year of diagnosis. Cox proportional hazards models were developed to evaluate association between patient characteristics and survival in men and female separately. All multivariable models included year of diagnosis and registry as stratification variable, marital status, treatment, primary site, and tumor grade and differentiation as covariates.