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


METHODS
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.


RESULTS
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.


RESULTS
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.
Department of Urology, Centre of Postgraduate Medical Education, European Health Centre Otwock, Poland. Electronic address: kubadobr@wp.pl.
Jakub
J
Dobruch
Institute of Urology, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
Siamak
S
Daneshmand
Department of Urology, University Medical-Center Hamburg-Eppendorf, Hamburg, Germany.
Margit
M
Fisch
Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Yair
Y
Lotan
Department of Surgery, Division of Urology, University of Toronto, Mount Sinai Hospital and University Health Network, Toronto, Canada.
Aidan P
AP
Noon
Department of Urologic Surgery, Vanderbilt University Medical Center and the Tennessee Valley VA Health Care System, Nashville, TN, USA.
Matthew J
MJ
Resnick
Department of Urology, Medical University of Vienna, Vienna, Austria.
Shahrokh F
SF
Shariat
Department of Surgery, Division of Urology, University of Toronto, Mount Sinai Hospital and University Health Network, Toronto, Canada.
Alexandre R
AR
Zlotta
Department of Urology, Mayo Clinic, Rochester, MN, USA.
Stephen A
SA
Boorjian
D002273:Carcinogens / Q000378:metabolism; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D012307:Risk Factors; D012737:Sex Factors; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000209:etiology / Q000378:metabolism / Q000401:mortality* / Q000473:pathology* / Q000628:therapy
D002273:Carcinogens; D012739:Gonadal Steroid Hormones
Androgen receptor; Bladder cancer; Estrogen receptor; Gender; Radical cystectomy; Urothelial carcinoma