Bladder cancer is the most common malignancy affecting the urinary system. In the United States, an estimated 68,810 new cases, with a male-to-female ratio of 4:1 and approximately 13,750 deaths, were expected to occur in 2008 [1]. The incidence of bladder cancer in the United States is higher in whites than in people of African or Asian descent, native Americans, or Latinos. However, survival is longer in white men than in men of other ethnic groups or in women. The disease has a median age at presentation of 70 years [1]. In the United States, the most common type of bladder cancer is urothelial carcinoma (UC), formerly known as “transitional cell” carcinoma (TCC).

UC arises from the mucosal lining of the bladder and is frequently multifocal. Numerous factors, including chromosomal markers, genetic polymorphisms, and genetic and epigenetic alterations, may be involved in tumorigenesis, progression, and metastasis. Seventy percent to eighty percent of patients with UC present with no muscle invasion (formerly known as “superficial disease”), and 20 percent to 30 percent present with muscle-invasive disease (Figure 37.1A). Despite a good prognosis for patients with non–muscle-invasive UC, recurrence is common and is associated with development of muscle-invasive disease in up to 30 percent of patients. In addition, 50 percent of patients presenting with muscle-invasive UC have occult distant metastases and a poor five-year survival rate.

ETIOLOGY AND PATHOGENESIS

Bladder cancer is commonly initiated by prolonged exposure to carcinogens that cause cumulative DNA damage in the urothelium (Figure 37.2).