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More than 350,000 new cases of bladder cancer are diagnosed per year worldwide. In the United States, bladder cancer is the 4th most common cancer, with 72,570 new cases in 2013 (1). Bladder cancer is three times more common in men (54,610 cases) than women (17,960 cases). There will be an estimated 15,210 deaths from bladder cancer in 2013. The median age at diagnosis is 65 years.

The best established risk factor for bladder cancer development is tobacco use, which is linked to 50% of bladder cancer cases (2). Carcinogens from tobacco are filtered from the blood into urine, and have sustained contact with urothelial cells lining the bladder, ureter, and renal pelvis. Tobacco-related cancer risk is dose dependent and diminishes with tobacco cessation. Pelvic irradiation and exposure to the chemotherapeutic cyclophosphamide also increase the risk of developing bladder cancer. In some areas of the world, chronic bladder inflammation caused by schistosomiasis is linked to a squamous cell subtype of bladder cancer.


Hematuria is the most common presenting symptom for bladder cancer. Hematuria may be gross or microscopic and is often painless, unless associated with clots and obstruction. Evaluation of asymptomatic patients for microscopic hematuria has not been an effective screening test for detection of bladder cancer.

When bladder cancer is suspected, workup should include urine cytology, cystoscopy, and an upper tract imaging study. Urine cytology has a sensitivity of 40%–60% with a specificity of greater than 90%. Spiral computed tomography (CT) can evaluate the upper urothelial tracts (renal pelvis and ureter), renal parenchyma, and lymph nodes. The definitive diagnosis can only be established by biopsy via transurethral resection of the bladder tumor (TURBT). Fluorescence in situ hybridization (FISH) of specific genes cannot be used to diagnose bladder cancer in the absence of a tissue biopsy, and the role of FISH in management of bladder cancer patients is not well established.

Transitional cell (urothelial) carcinoma is the most common subtype of bladder cancer (>90%), and can arise in other organs lined by transitional epithelium, including renal pelvis, ureter, and the proximal two-thirds of the urethra. Other histologic subtypes include squamous cell carcinoma (3% of bladder tumors in the United States), adenocarcinoma (2%; includes tumors at the bladder dome originating from the urachal remnant), and small cell tumors (1%). Further classification of transitional cell carcinoma subtypes includes the particularly aggressive micropapillary and sarcomatoid histologies. The remainder of this chapter will discuss management of transitional cell carcinoma.


Urinary bladder cancer can be grouped into three general categories by stage at presentation: non-muscle-invasive (formerly described as superficial), muscle-invasive, and metastatic. Each differs in clinical behavior, primary management, and outcome.

The primary bladder tumor is staged according to the depth of invasion into the bladder ...

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