1. Epidemiology and Natural History

The incidence of bladder cancer varies substantially between different geographic regions, which can in part be attributed to regional differences in exposures, although differences in reporting may also play a role. In general, the incidence tends to be higher in developed countries than less developed ones. In all geographic regions, men are much more likely to be diagnosed with bladder cancer than women, and within each sex the risk of bladder cancer diagnosis increases considerably with age. Smoking remains the most important known modifiable risk factors for bladder cancer development, although other occupational and environmental exposures exist.

The true natural history of untreated bladder cancer is not known because the disease is almost always discovered during the patient’s lifetime, most frequently due to hematuria, and is treated at least by transurethral resection. The natural history of treated bladder cancer (i.e., the expected clinical course) is highly variable, depending on tumor characteristics at presentation. On the one side of the spectrum are the low-grade urothelial cancers confined to the bladder surface which, despite frequent local recurrences, rarely progress and typically do not pose a threat to a patient’s life. On the other side are the high-grade muscle-invasive lesions that often produce early metastases and cause death despite aggressive treatment.