Within the United States, urothelial carcinoma of the bladder and urinary tract are most closely related to tobacco smoking history. However, within developing countries water supplies contaminated with arsenic or schistosomiasis parasites also are major carcinogenic contributors.
Cancers of the urinary tract including the bladder, renal pelvis, ureter, and urethra occur frequently, and they represent the second most common class of genitourinary cancers. Bladder cancer alone represents the fifth most common cancer diagnosis annually in the United States with >76,000 new cases and 16,000 deaths every year. Because cancers of the renal pelvis are often lumped in with all kidney cancers, the true incidence and mortality from nonbladder urinary tract cancers are less precise. While less frequent than bladder cancer, an additional 20,000 new cases and 5000 deaths are estimated every year. While significant advances in therapy options and improvements in patient outcomes have rapidly occurred in many cancers in the past decade, progress in urinary tract cancers has lagged. Fortunately, an accelerated understanding of the molecular underpinnings of bladder and urinary tract cancer biology has led to a significant increase in clinical trials with the first U.S. Food and Drug Administration (FDA) approval of a new drug for advanced bladder and urinary tract cancers in over 25 years with many more expected to follow. This chapter reviews the established, current, and emerging evidence that serves as the basis for the rapidly evolving standards of care for patients with bladder and urinary tract cancers.
CLINICAL EPIDEMIOLOGY AND RISK FACTORS
Bladder cancer typically affects older patients with a median age at diagnosis of 73 years. Males are four times more frequently affected than females. Similarly, bladder cancer is more common in Caucasians than in Asian patients. Singular inheritable genetic risk factors are rare in patients with bladder or urinary tract cancers. Patients with defects in mismatch repair genes leading to microsatellite instability (MLH1, MSH2, MSH6, etc.) as part of the familial cancer Lynch syndrome are at particular risk of upper urinary tract cancers of the renal pelvis and ureter. Additionally, patients with Cowden disease (PTEN mutations) or retinoblastoma (RB1 mutations) are at increased risk for developing bladder cancer.
Historically, associations have existed between environmental toxic exposures and higher rates of developing bladder cancer. Carcinogenic agents associated with increased risk of bladder cancer have included the aromatic amines benzidine and beta-naphthylamine that can be present in industrial dyes as well as arsenic that can be found in some drinking water supplies in underdeveloped countries. Other chemicals in the leather, paint, rubber, textiles, and printing industries have been associated with bladder cancer. More recently, associations with exposures to hair dyes and hair sprays in workers in the hairstyling field have been suggested. Additionally, much concern has been raised regarding use of the antidiabetic medication, pioglitazone, and bladder cancer risk. ...