Objectives: It has consistently been shown that women who are diagnosed with bladder cancer have lower survival than men, but the exact mechanism remains unknown. Most studies assumed that the sex-specific mortality ratio is constant over time, possibly resulting in inaccurate estimates in various periods of follow-up. This study aimed to investigate the sex-specific excess mortality in bladder cancer patients and its variation over follow-up time. Methods: Observational cohort study. Using data from the population-based Netherlands Cancer Registry, we studied 24,169 patients diagnosed between 2003 and 2014 with histologically confirmed ≥T1 bladder cancer with follow-up until January 2018. We used flexible parametric relative survival models to estimate excess mortality as a function of time for each sex and to explore the effect of covariates on these functions. Results: Female patients (24%) had worse clinical tumor, node, and metastasis-stage at diagnosis and more often a nonurothelial tumor histology. The excess mortality ratio of sex was not constant over time; in the first two years after diagnosis excess mortality rates for women were higher than for men, but lower thereafter; this applied to both nonmuscle-invasive and muscle-invasive bladder cancer subgroups. Baseline differences in age, tumor, node, and metastasis-stage and histology accounted for only part of the excess mortality gap. Conclusions: The assumption of proportional hazards over time leads to underestimation of the excess mortality ratio for women in the first two years and overestimation thereafter, when excess mortality is comparable for women and men. Clinicians should incorporate the initial sex-specific poorer outcome in their considerations regarding prognosis and treatment options for female patients, e.g., more invasive treatment and neo-adjuvant treatment. These findings also point towards a mechanism of micrometastatic disease, warranting assessment of sex-specific efficacy in randomized controlled trials on treatments in this patient population. 2019 Elsevier Inc. All rights reserved.

Additional Metadata
Keywords Bladder cancer, Sex differences, Gender differences, Prognosis, Survival
Persistent URL dx.doi.org/10.1016/j.urolonc.2019.08.001, hdl.handle.net/1765/122276
Journal Urologic Oncology
Citation
Richters, A, Dickman, P.W., Witjes, J.A, Boormans, J.L, Kiemeney, L.A.L.M, & Aben, K.K.H. (2019). Bladder cancer survival: Women only fare worse in the first two years after diagnosis. Urologic Oncology, 37(12), 853–861. doi:10.1016/j.urolonc.2019.08.001