Ingestion of large quantities of arsenic in well water has also been associated with numerous malignancies, including TCC of the bladder.[22,23] Similar endemic pockets of bladder cancer are found in other regions with high arsenic concentrations in drinking water. In South Taiwan, arsenic blackfoot disease is endemic.
Additional risk factors associated with more aggressive forms of bladder cancer include prolonged exposures to urinary foreign bodies and infections; neuropathic bladder and associated indwelling catheters;[25,26]Schistosoma haematobium bladder infections (Bilharzial bladder cancer); exposure to the cancer chemotherapy agent cyclophosphamide [28,29,30,31] and perhaps other alkylating agents, such as ifosfamide (although the use of mesna in conjunction with these agents may reduce the incidence); and pelvic radiation therapy for other malignancies.[33,34,35] Renal transplant recipients appear to have an increased incidence of bladder cancer.
Urothelial tumors other than TCC include adenocarcinoma, squamous cell carcinoma, and metastatic adenocarcinoma. Risks for squamous cell tumors in the bladder include indwelling catheters [37,38] and S. haematobium cystitis.
Adenocarcinomas account for less than 2% of primary bladder cancers, including metastases from the rectum, stomach, endometrium, breast, prostate, and ovary.
Although occasional familial clusters have been anecdotally reported [39,40,41] and bladder cancer (as well as upper urinary tract TCC) is part of the Lynch family cancer syndrome II, there is no evidence that tendencies towards developing bladder cancer are inherited.
Seventy percent of patients with bladder cancer have superficial disease at presentation. Hematuria is the most common presenting sign, occurring in about 90% of cases. Hematuria may be intermittent, so a urinalysis without red blood cells does not exclude a diagnosis of urothelial cancer. In patients with macroscopic hematuria, the reported rates of bladder cancer range from 13% to 34.5%.[45,46,47] Other presenting symptoms include dysuria, urinary frequency or urgency, and less commonly, flank pain secondary to obstruction, and pain from pelvic invasion or bone metastases. Diagnosis and staging usually begin with cystoscopy. Full evaluation of the upper and lower urinary tract is required.