Gender Disparities in the Clinical Trials and Real-World Utilization of Systemic Therapy in the Management of Urothelial Carcinoma

Objectives: The objectives of this study was (1) to examine the representation of women in clinical trials for systemic therapy in muscle-invasive (MIBC) or metastatic bladder cancer (BC) and (2) to determine the association between sex and systemic therapy in the treatment of MIBC or metastatic BC. Methods: A review of bladder cancer systemic therapy clinical trials cited by the National Comprehensive Cancer Network guidelines was performed. Proportions of women were compared with the corresponding proportions in the US population with bladder cancer between 1975 and 2018, based on the Surveillance, Epidemiology, and End Results database. We also used the National Cancer Database (NCDB) to identify 55,951 patients with American Joint Committee on Cancer clinical stage II, III, and IV bladder cancer between 2004 and 2015. We determined the predictors of systemic therapy for bladder cancer treatment using a multivariable logistic regression model. Results: 26.9% of the US bladder cancer population were women; however, only 17.7% of participants in US clinical trials and 19.9% of participants in all clinical trials were female, indicating an absolute difference of 9.2% (95% confidence interval [CI]: 6.2%-12.1%; P < .001) and 7.0% (95% CI: 6.1%-7.9%; P < .001), respectively. Multivariable analysis of the NCDB showed that women had decreased odds of receiving systemic therapy compared with male patients with MIBC or metastatic BC (odds ratio: 0.93, 95% CI: 0.89-0.96; P < .001). Conclusion: Women are underrepresented in MIBC and/or metastatic BC systemic therapy clinical trials. In addition, women are less likely than men to receive systemic therapy for the treatment of MIBC or metastatic BC. Further research is needed to investigate the reasons for gender disparities in treatment of MIBC or metastatic BC as well as the participation in clinical trials.