BLADDER CANCER

Bladder cancer: epidemiology and aetiology
Bladder cancer is the second most common urological malignancy, accounting for 4973 deaths in the UK in 2001. This represents 3% of all cancer deaths. Incidence is ~13,000 per year, indicating that the majority of patients have curable or controllable disease.

Risk factors
- Men are 2.5 times more likely to develop the disease than women, the reasons for which are unclear but may be associated with greater urine residuals in the bladder.
- Age increases risk, most commonly diagnosed in the 8th decade and rare <50 years.
- Racially, Black people have a lower incidence than White people, but inexplicably they appear to carry a poorer prognosis.
- Environmental carcinogens, found in urine, are the major cause of bladder cancer.
- Chronic inflammation of bladder mucosa: bladder stones, long-term catheters, and, notoriously, the ova of Schistosoma haematobium (bilharziasis) are implicated in the development of squamous cell carcinoma of the bladder.
- Smoking is the major cause of bladder cancer in the developed world. Cigarette smoke contains the carcinogens 4-aminobiphenyl (4-ABP) and 2-naphthylamine. Slow hepatic acetylation (detoxification) of 4-ABP by N-acetyltransferase and glutathione S-transferase M1 (GST M1), or induction of the cytochrome p-450 1A2 demethylating enzyme, appear to increase urinary carcinogenic exposure of the urothelium. Smokers have a 2 - 5-fold risk compared to non-smokers, with respect to development of bladder cancer and subsequent recurrences. Estimates suggest that 30 - 50% of bladder cancer is caused by smoking. There is a slow (20-year) reduction in risk following cessation of smoking.
- Occupational exposure to carcinogens, in particular aromatic hydrocarbons like aniline, is a recognized cause of bladder cancer. See the box for examples of  at risk occupations. A latent period of 25 - 45 years exists between exposure and carcinogenesis.
- Drugs: phenacitin and cyclophosphamide.
- Pelvic radiotherapy.

No evidence for a hereditary genetic aetiology exists, though many somatic genetic abnormalities have been identified. The most common cytogenetic abnormality is loss of chromosomes 9p, 9q, 11p 13q, and 17q. Activation/ amplification of oncogenes (p21 ras, c-myc, c-jun, erbB-2), inactivation of tumour suppressor genes (p53 mutations appear to worsen survival after treatment, retinoblastoma, p16 cyclin-dependent kinse inhibitor), and increased expression of angiogenic factors (e.g. vascular endothelial growth factor, VEGF) are reported in transitional cell carcinomas.

Bladder cancer: pathology and staging
Benign tumours of the bladder, including inverted papilloma and nephrogenic adenoma, are uncommon.
The vast majority of primary bladder cancers are malignant and epithelial in origin:
- >90% are transitional cell carcinoma (TCC)
- 1 - 7% are squamous cell carcinoma (SCC)
- 75% are SCC in areas where schistosomiasis is endemic
- 2% are adenocarcinoma
- Rarities include phaeochromocytoma, melanoma, lymphoma, and sarcoma arising within the bladder muscle
- Secondary bladder cancers are mostly metastatic adenocarcinoma from gut, prostate, kidney, or ovary

Tumour spread
- Direct tumour growth to involve the detrusor, the ureteric orifices, prostate, urethra, uterus, vagina, perivesical fat, bowel, or pelvic side walls.
- Implantation into wounds/percutaneous catheter tracts.
- Lymphatic infiltration of the iliac and para-aortic nodes.
- Haematogenous, most commonly to liver (38%), lung (36%), adrenal gland (21%), and bone (27%). Any other organ may be involved.

Histological grading
is divided into: well, moderately, and poorly differentiated (abbreviated to G1, G2, and G3 respectively).
Staging
is by the TNM (1997) classification. All rely upon physical examination and imaging, the pathological classification (prefixed p) corresponding to the TNM categories.