Sex Differences in Melanoma Survival are Not Related to Mitotic Rate of the Primary Tumor

Based on prior studies, we concluded that the female advantage in melanoma survival is caused by biological factors and not by differences in patient behavior. In this study, we investigated whether this biological advantage was caused by more aggressive tumors in males, as measured by mitotic rate (MR). Data for patients with complete information on MR, Breslow thickness, ulceration and primary tumor location were extracted from the database of Melanoma Institute Australia in Sydney. A negative binomial regression model was used to assess the independent predictive value of sex for MR. Also, the impact of MR on the sex survival advantage was investigated using Cox proportional hazards models. A total of 9,306 patients were included in the analysis. Although males had a slightly higher MR at diagnosis, sex was not an independent predictor of MR after adjustment for all other prognostic factors: incidence rate ratio 0.98, 95 % confidence interval (CI) 0.93-1.02, p = 0.32. After adjustment for all prognostic factors, females had a survival advantage of 36 % (hazard ratio 0.65, 95 % CI 0.55-0.75, p < 0.001). When added as a confounder, MR did not influence this sex hazard ratio. Sex did not independently predict the aggressiveness of a primary melanoma. Furthermore, MR did not influence the known female survival advantage. Based on these results, the biological trait underlying sex survival differences in melanoma seems not to be tumor-related and therefore is more likely to be caused by host factors.