More than 70,000 new cases of bladder cancer occur each year in the United States, and more than 14,000 deaths per year can be attributed to it. The lifetime probability of incurring cancer of the bladder is approximately 3% for white men and 1% for white women. Cancer of the lower urinary tract is a tumor of older age groups; in the United States, the mean age at the time of diagnosis is 68 years. The incidence increases at a constant rate during adult life, varying from 1 in 100,000 per year at age 20 years to 200 in 100,000 per year at age 80 years for white men. Women have approximately one third of the risk of men. In the United States, whites are twice as likely to have bladder tumors as nonwhites. Urban dwellers have consistently been shown to have a higher incidence of lower urinary tract tumors than do people who live in rural or suburban areas.

The most notable risk factor for the development of lower urinary tract cancers is occupational exposure to aromatic amines, which was first noted in England in 1895. Subsequently, dyestuff workers were shown to have a 10- to 50-fold increased risk for bladder carcinoma. Compounds most closely associated with bladder carcinogenesis include 2-naphthylamine and benzidine. Case-control studies indicate an excess risk among men who work with dyestuffs, rubber, leather, paints, and organic chemicals. It has been estimated that these occupational exposures are responsible for 18% of bladder cancer cases. As little as 2 years of exposure may be sufficient to increase the risk, but the time between exposure and subsequent cancer may be as long as 45 years.

Smoking represents an important risk factor for bladder cancer. Current studies find the risk in smokers compared to nonsmokers is greater than previously reported (hazard ratio 4.06), believed to be related to higher concentrations of bladder carcinogens in the smoke of current cigarette formulations.

Other suggested risk factors include pelvic irradiation, which was used in the past for dysfunctional bleeding and continues to be used for cancer of the prostate, cervix, and ovaries. The abuse of phenacetin-containing analgesics is also a risk factor. Early case-control studies suggested an association with coffee consumption, but the weight of evidence does not support a significant increase in risk. Occupational exposure to hair dyes has been implicated, but there is no association with the personal use of such dyes. Exposure to diesel exhaust as a risk factor is suggested by a modest increase in incidence among truck and bus drivers.

Because direct contact of the bladder urothelium with carcinogens excreted in the urine may contribute to bladder cancer, it has been hypothesized that a high consumption of fluids could reduce risk by diluting the urine or reducing contact time. Evidence has been inconsistent, but the largest prospective study suggests that men in the highest quintile of fluid consumption face about half of the risk of those in the lowest quintile. Case-control and cohort studies also suggest that long-term use of diuretics may increase the risk for bladder cancer by as much as twofold.

The natural history of lower urinary tract tumors is not welldefined. The prognosis at the time of diagnosis depends on both clinical stage, defined by the depth of penetration and the extent of metastases, and histologic grade of the tumor. The depth of penetration and histologic grade are often closely correlated. Urothelial tumors are grossly subdivided into papilloma, papillary carcinoma, and transitional cell carcinoma. These gross morphologic distinctions have histologic counterparts that are highly predictive of 5-year survival. Grade 1 papillary carcinoma (papilloma) has a 5-year cure or clinical control rate of approximately 95%. Grade 2 papillary carcinoma (papillary carcinoma) has a 5-year survival rate of only 25%. The outlook for grade 3 papillary and infiltrating carcinoma (transitional cell carcinoma) is worse. The prognosis for patients with squamous carcinoma is also very poor unless the tumor is well-differentiated.

Clinical staging systems that distinguish among levels of tumor penetration of the bladder have also been shown to have good prognostic value. Overall, about 50% of patients with treated bladder cancer survive for 5 years. However, multiple synchronous and asynchronous tumors are the rule in lower urinary tract cancer and contribute to morbidity and eventual mortality. Hematuria is the most common presentation of lower urinary tract cancer. Other symptoms suggestive of cystitis may also occur. Although it has been claimed that 75% of tumors promptly diagnosed after a first episode of hematuria are localized, few data on this subject are available. The likelihood that screening tests, including urinalysis and urinary cytology, would significantly advance the time of diagnosis is unproven. A progression from urothelial atypia to sessile carcinoma in situ or papilloma to higher-grade malignancy has been postulated. Studies of the natural history of urothelial carcinoma in situ indicate that the majority of lesions progress to more malignant forms. Although early lesions are much less likely to be detected cytologically, 3.7% of detected tumors were in situ in one study. The usual synchronous and asynchronous multiplicity of such tumors make it difficult to assess the benefits of early detection.