Persistent disparities in outcomes between men and women with bladder cancer highlight areas of needed improvement in the delivery of oncologic care. There were approximately 81,190 new cases of bladder cancer in the United States in 2018, and the majority of these cases were in men. While males are three to four times more likely to develop the disease, women tend to present with advanced stage, experience differences in quality of life following treatment, and suffer worse cancer-specific mortality (Surveillance, Epidemiology, and End Results [SEER] Program Populations [1992-2018], www.seer.cancer.gov/popdata, released 2018).
Based on Surveillance, Epidemiology, and End Results (SEER) data, women appear to have better cancer-specific mortality for most malignancies; however, this does not appear to be the case for bladder cancer (Cancer Epidemiol Biomarkers Prev 2011; 20:1629–37). Epidemiologic and biologic explanations have been offered, but our incomplete understanding of the issue suggests numerous contributing factors.
In this article, we examine these factors, with a focus on current research that elucidates their role in the bladder cancer gender disparity. The table provides a summary of these research findings.
Disparities in evaluation and diagnosis
Perhaps the most evident disparity confronting female patients with bladder cancer relates to timely evaluation and diagnosis. The reasons for this are multifaceted and reflect differences in how female patients with hematuria progress through the health care system. Interpretation of hematuria in the female patient can be challenging for primary care physicians. While hematuria is certainly concerning for malignancy, it is also present in a number of benign conditions, including urinary tract infections, which are common in postmenopausal females.
In a large population study performed by Cohn and colleagues, women presenting with hematuria who were ultimately diagnosed with bladder cancer were far more likely to be treated for a suspected urinary tract infection during initial evaluation than males (Cancer 2014; 120:555-561). Similarly, evaluation of practice patterns of primary care physicians by Buteau and colleagues demonstrated that women presenting with hematuria often underwent three or more pre-referral consultations with their primary care provider for the same complaint before referral for urologic evaluation (OR: 2.31, 95% CI: 1.98–2.69) (Urol Oncol 2014; 32:128-34).
It is possible that these barriers are the result of conflicting guidelines regarding the evaluation of asymptomatic microscopic hematuria. While the AUA defines microscopic hematuria as greater than 3 red blood cells per high powered field as the trigger for further diagnostic evaluation, 2017 guidelines from the American College of Obstetricians and Gynecologists favor a cutoff of 25 red blood cells per high powered field for non-smoking women under 50 years of age. This may lead to confusion for primary care physicians as to when referral is appropriate. Similarly, women who present to their gynecologist for evaluation of microscopic hematuria may experience delays in urologic referral.
While individually, these factors likely play only a small role in the overall delay in evaluation, the effect is notable. Cohn and colleagues demonstrated that women were more likely to experience a delay in time to diagnosis when compared to men (85.4 days vs. 73.6 days; p<.001) and a higher rate of >6-month delay in diagnosis (17.3% vs. 14.1%; p<.001) (Cancer 2014; 120:555-61). It has been well documented that delays in diagnosis translate to poorer cancer-specific outcomes (J Urol 2003; 169:110-5).