Elsevier

European Urology

Volume 69, Issue 2, February 2016, Pages 300-310
European Urology

Collaborative Review – Bladder Cancer
Gender and Bladder Cancer: A Collaborative Review of Etiology, Biology, and Outcomes

https://doi.org/10.1016/j.eururo.2015.08.037Get rights and content

Abstract

Context

The incidence of bladder cancer is three to four times greater in men than in women. However, women are diagnosed with more advanced disease at presentation and have less favorable outcomes after treatment.

Objective

To review the literature on potential biologic mechanisms underlying differential gender risk for bladder cancer, and evidence regarding gender disparities in bladder cancer presentation, management, and outcomes.

Evidence acquisition

A literature search of English-language publications that included an analysis of the association of gender with bladder cancer was performed using Pubmed. Ninety-seven articles were selected for analysis with the consensus of all authors.

Evidence synthesis

It has been shown that the gender difference in bladder cancer incidence is independent of differences in exposure risk, including smoking status. Potential molecular mechanisms include disparate metabolism of carcinogens by hepatic enzymes between men and women, resulting in differential exposure of the urothelium to carcinogens. In addition, the activity of the sex steroid hormone pathway may play a role in bladder cancer development, with demonstration that both androgens and estrogens have biologic effects in bladder cancer in vitro and in vivo. Importantly, gender differences exist in the timeliness and completeness of hematuria evaluation, with women experiencing a significantly greater delay in urologic referral and undergoing guideline-concordant imaging less frequently. Correspondingly, women have more advanced tumors at the time of bladder cancer diagnosis. Interestingly, higher cancer-specific mortality has been noted among women even after adjusting for tumor stage and treatment modality.

Conclusions

Numerous potential biologic and epidemiologic factors probably underlie the gender differences observed for bladder cancer incidence, stage at diagnosis, and outcomes. Continued evaluation to define clinical applications for manipulation of the sex steroid pathway and to improve the standardization of hematuria evaluation in women may improve future patient outcomes and reduce these disparities.

Patient summary

We describe the scientific basis and clinical evidence to explain the greater incidence of bladder cancer in men and the adverse presentation and outcomes for this disease in women. We identify goals for improving patient survival and reducing gender disparities in bladder cancer.

Introduction

Bladder cancer is the ninth most common malignancy and 13th most common cause of cancer death worldwide [1]. According to estimates, 74 000 cases of urothelial carcinoma of the bladder (UCB) will be diagnosed in the USA in 2015, with 16 000 bladder cancer deaths [2]. Interestingly, it has been found that bladder cancer diagnosis is three to four times more common in men than in women, so that UCB represents the fourth most common cancer in men in the USA and the eighth most common cause of cancer death [2], [3]. Moreover, between 1998 and 2008, the rate of increase in the number of bladder cancer cases in the USA was 25% faster in men than in women [4]. Numerous explanations for this gender discrepancy in incidence have been offered, including disparate exposures to bladder cancer risk factors and the potential for sex steroid hormone regulation.

At the same time, women diagnosed with bladder cancer are more likely to have locally advanced tumors at the time of diagnosis [5]. Furthermore, female gender has been reported—albeit not uniformly—to be associated with higher risks of disease recurrence, progression, and mortality after treatment [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24]. Understanding the factors associated with gender disparities in bladder cancer presentation, evaluation, and management could thus facilitate improvements in the timeliness and intensity of health care delivery. In turn, such efforts offer the potential to reduce the magnitude of the gender-based disparities observed for bladder cancer outcomes.

The aim of the present review was to assess the literature on potential biologic mechanisms underlying the gender discrepancy in bladder cancer incidence and the epidemiologic evidence demonstrating disparities in bladder cancer evaluation, management, and outcomes between men and women.

Section snippets

Evidence acquisition

A literature search using the MEDLINE/Pubmed database was performed to identify original articles, review articles, and editorials published between 1966 and 2015 that included an analysis of the association of gender with bladder cancer. The search was limited to studies published in the English language. No manual search of meeting abstracts was performed. The following keywords were used during the search: urothelial cancer, bladder cancer, sex, gender, males, females, men, women, androgen

Impact of gender-specific risk factor exposure on the gender discrepancy in bladder cancer incidence

The association between risk factor exposures and bladder cancer development has been extensively investigated [25], [26]. In particular, cigarette smoking has been well established as the most common risk factor for bladder cancer diagnosis [27]. Currently, an estimated 42.1 million US adults smoke, corresponding to 15.3% of adult women and 20.5% of adult men [28]. The global modeled age-standardized prevalence of smoking in the population older than 15 yr decreased from 41.2% in 1980 to 31.1%

Conclusions

The relationship between gender and UCB is complex, and is probably influenced by both biologic and epidemiologic factors. While the incidence of bladder cancer is three- to fourfold higher in men, women are diagnosed with more advanced stage tumors. Moreover, consistent but not universal data suggest higher mortality from bladder cancer among women compared to men. Numerous potential contributing factors may explain these demographic trends, including the importance of the sex steroid hormone

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