A Primer on Urothelial Cancer

September 21, 2020 by Kristine B. LeFebvre DNP, RN, NPD-BC, AOCN®

The urinary system, including the bladder, ureters, urethra, and renal pelvis, is lined with urothelial tissue. Urothelial carcinoma is the predominant histologic type of cancer in that system, and 90% of tumors are located in the bladder. With more than 81,400 new cases and nearly 18,000 deaths estimated (https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2020/cancer-facts-and-figures-2020.pdf) for 2020, bladder cancer is the fifth most prevalent type of cancer in the United States.

When diagnosed early, bladder cancer has a 97% survival rate (https://doi.org/10.1111/iju.13376). However, five-year survival with metastatic disease drops to 22%.

Risk Factors

Men are at the highest risk for bladder cancer and are four times more likely to be diagnosed than women, with incidence higher in Caucasian men than African American men. The median age (https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2020/cancer-facts-and-figures-2020.pdf) at diagnosis is 73, with most cases found in (https://www.ons.org/books/cancer-nursing-principles-and-practice-eighth-edition) those older than 55.

Smoking significantly increases risk for bladder cancer. Additional contributing factors include (https://accessmedicine-mhmedical-com.ezproxy.lib.umb.edu/content.aspx?bookid=2840&sectionid=241657936) occupational chemical exposure, arsenic in drinking water, damage to the bladder from chemotherapy treatment, and physical trauma from repeated infections. Rarely, cases are linked (https://doi.org/10.1111/iju.13376) to genetic syndromes and relatives of those with bladder cancer diagnosed before age 60.

Diagnosis and Staging

Bladder cancer has no screening tests (https://doi.org/10.1038/nrurol.2017.11) and currently no reliable biomarkers (https://doi.org/10.1111/ajco.13059) because of heterogeneity of genetic variants. The presenting symptom for most bladder cancers is hematuria. Other symptoms include urinary urgency, frequency, and dysuria. Large or invasive tumors may present (https://accessmedicine-mhmedical-com.ezproxy.lib.umb.edu/content.aspx?bookid=2840&sectionid=241657936) as a palpable mass with lymphadenopathy.

Diagnostic workup for bladder cancer includes (https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf) a history and physical, cystoscopy, and abdominal or pelvic imaging of the upper urinary tract collecting system, with the possible addition (https://accessmedicine-mhmedical-com.ezproxy.lib.umb.edu/content.aspx?bookid=2840&sectionid=241657936) of computed tomography (CT) urography, magnetic resonance imaging, and positron-emission tomography CT for staging. The American Urologic Association does not recommend (https://www.auanet.org/guidelines/asymptomatic-microhematuria-(amh)-guideline) the use of urine cytology and urine markers (NMP22, BTA-stat, and UroVysionFISH) as part of the evaluation for asymptomatic microhematuria, but they may be useful if a patient has high risk factors.

Bladder cancer is staged using the American Joint Committee on Cancer tumor-node-metastasis staging system. At diagnosis, 75% of tumors are localized and 25% have regional and distant metastases. Invasive bladder cancers metastasize (https://accessmedicine-mhmedical-com.ezproxy.lib.umb.edu/content.aspx?bookid=2840&sectionid=241657936) most commonly (https://doi.org/10.1200/jop.2017.022137) to the lymph nodes, lungs, and bone.


Cystoscopy and transurethral resection (TUR) are used for diagnosis and initial staging. If the cancer is not muscularly invasive, the TUR will be followed postoperatively with a single dose of intravesicular chemotherapy or bacillus Calmette Guérin (BCG). If needed, subsequent doses of intravesicular chemotherapy (https://accessmedicine-mhmedical-com.ezproxy.lib.umb.edu/content.aspx?bookid=2840&sectionid=241657936) or BCG (https://doi.org/10.1016/j.ctrv.2018.06.002) may be used.

Locally invasive tumors (T2 or T3) may be treated with a partial or radical cystectomy with or without a combination of radiation and systemic chemotherapy. Unresectable tumors may be treated with (https://accessmedicine-mhmedical-com.ezproxy.lib.umb.edu/content.aspx?bookid=2840&sectionid=241657936) neoadjuvant chemotherapy, followed by surgery or radiation.

Advanced urothelial cancer is treated with systemic antineoplastic therapy, most commonly cisplatin. It may be used (https://accessmedicine-mhmedical-com.ezproxy.lib.umb.edu/content.aspx?bookid=2840&sectionid=241657936) as a single therapy or combined with other regimens. Neoadjuvant chemotherapy is often used with bladder-sparing surgical approaches. Immunotherapy with checkpoint inhibitors, specifically PD-L1 and PD-1 inhibitors, have shown promise (https://doi.org/10.1200/jop.2017.022137), as well as a newly approved antibody-drug conjugate (https://ascopubs.org/doi/10.1200/JCO.19.01140).

An ONS initiative is developing resources related to urothelial and bladder cancers, how they are treated, and how best to support your patients and their families.

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