Urinary bladder cancer is the 11th most common cancer when considering both sexes together and the 7th most common in men. It is associated in particular with cigarette smoking, blood fluke infections (Schistosoma haematobium), and some occupational exposures. Most of bladder cancers arise from transitional epithelium (urothelium) lining the bladder (“urothelial carcinomas”). Non-invasive urothelial neoplasms are precursor lesions of invasive urothelial carcinoma. This entry is devoted mainly to urothelial carcinoma but the pathology and genetics of some other bladder lesions are also briefly discussed.
Bladder carcinogenesis is hypothesized to occur through multiple oncogenic events in multiple urothelial sites, transforming stem cells into cancer stem cells which then form tumors. Recent genomic studies have depicted two independent pathways involved in this process: the MAP signaling (which includes FGFR3) and the p53 signaling pathway. Activating FGFR3 mutations are associated with non-invasive lesions, while TP53 mutations or mutations in genes regulating p53 are associated with high-grade lesions. Molecular subtyping has identified several distinct molecular subtypes, and a new bladder cancer classification based on histomolecular tumor features is likely to follow.
Most bladder cancer patients present with hematuria. The diagnosis and staging are based on cystoscopy, bimanual examination, and a pathologic evaluation of biopsy or transurethral resection, with the evaluation of the presence and extent of invasion being crucial parameters. A number of urine biomarker tests for non-invasive diagnosis and follow-up have been developed but none of them has yet been clinically validated. Despite high recurrence rates, bladder cancer patients usually have good prognosis. Non-muscle invasive bladder cancers are most commonly managed by transurethral resection of the bladder, carcinomas in situ—by cytoscopic resection and Bacillus Calmette-Guerin (BCG) treatment, and invasive tumors—by a combination of radical cystectomy and perioperative chemotherapy. Targeted immunotherapeutics, such as checkpoint inhibitors, seem to be the future of bladder cancer treatment.