Biological differences underlying sex and gender disparities in bladder cancer: current synopsis and future directions

Abstract Sex and gender disparities in bladder cancer have long been a subject of interest to the cancer research community, wherein men have a 4 times higher incidence rate than women, and female patients often present with higher-grade disease and experience worse outcomes. Despite the known differences in disease incidence and clinical outcomes between male and female bladder cancer patients, clinical management remains the same. In this review, we critically analyze studies that report on the biological differences between men and women and evaluate how these differences contribute to sex and gender disparities in bladder cancer. Distinct characteristics of the male and female immune systems, differences in circulating hormone levels and hormone receptor expression, and different genetic and epigenetic alterations are major biological factors that all likely contribute to disparate incidence rates and outcomes for male and female bladder cancer patients. Future preclinical and clinical studies in this area should employ experimental approaches that account for and consider sex and gender disparities in bladder cancer, thereby facilitating the development of precision medicine for the effective treatment of bladder cancer in all patients