eMedicine Specialties > Urology > Cancer, Bladder, Penis, and Urethra
Bladder Cancer
Updated: Mar 7, 2008
Introduction
Background
Bladder cancer is a common urologic cancer. The most common type of bladder cancer in the United States is urothelial carcinoma, formerly known as transitional cell carcinoma (TCC). The urothelium in the entire urinary tract may be involved, including the renal pelvis, ureter, bladder, and urethra.
The clinical course of bladder cancer carries a broad spectrum of aggressiveness and risk. Low-grade, superficial bladder cancers have minimal risk of progression to death; however, high-grade muscle-invasive cancers are often lethal.
Pathophysiology
Almost all bladder cancers are epithelial in origin. The urothelium consists of a 3- to 7-cell mucosal layer within the muscular bladder. Of these urothelial tumors, more than 90% are transitional cell carcinomas. However, up to 5% of bladder cancers are squamous cell in origin, and 2% are adenocarcinomas. Nonurothelial primary bladder tumors are extremely rare and may include small cell carcinoma, carcinosarcoma, primary lymphoma, and sarcoma.
Bladder cancer is often described as a polyclonal field change defect with frequent recurrences due to a heightened potential for malignant transformation. However, bladder cancer has also been described as a problem with implantation and migration from a previously affected site.
The World Health Organization classifies bladder cancers as low grade (grade 1 and 2) or high grade (grade 3). Tumors are also classified by growth patterns: papillary (70%), sessile or mixed (20%), and nodular (10%). Carcinoma in situ (CIS) is a flat, noninvasive, high-grade urothelial carcinoma. The most significant prognostic factors for bladder cancer are grade, depth of invasion, and the presence of CIS.
Upon presentation, 55-60% of patients have low-grade superficial disease, which is usually treated conservatively with transurethral resection and periodic cystoscopy. Forty to forty-five percent of patients have high-grade disease, of which 50% is muscle invasive and is typically treated with radical cystectomy.
Less than 5% of bladder cancers in the United States are squamous cell carcinomas (SCCs). However, worldwide, SCC is the most common form, accounting for 75% of bladder cancer in underdeveloped nations. In the United States, SCC is associated with persistent inflammation from long-term indwelling Foley catheters and bladder stones. In underdeveloped nations, SCC is associated with bladder infection by Schistosoma haematobium.
Adenocarcinomas account for less than 2% of primary bladder tumors. These tumors are observed most commonly in exstrophic bladders and respond poorly to radiation and chemotherapy. Radical cystectomy is the treatment of choice.
Small cell carcinomas are aggressive tumors associated with a poor prognosis and are thought to arise from neuroendocrine stem cells.
Carcinosarcomas are highly malignant tumors that contain both mesenchymal and epithelial elements.
Primary bladder lymphomas arise in the submucosa of the bladder and are treated with radiation therapy.
Leiomyosarcoma is the most common sarcoma of the bladder.
Rhabdomyosarcomas most commonly occur in children and carry a poor prognosis.
Frequency
United States
Bladder cancer is the fourth most common cancer in men in the United States, after prostate, lung, and colorectal cancer. Bladder cancer is the 10th most common cancer in women. From 1985-2000, the number of patients diagnosed annually with bladder cancer increased by 33%. An annual cohort of 300,000-400,000 patients with bladder cancer is reported in the United States. The recurrence rate for superficial transitional cell cancer of the bladder is high, and as many as 80% of patients have at least one recurrence.
International
In developed countries, 90% of bladder cancers are TCC. In developing countries, 75% of bladder cancers are SCCs, and most of these cancers are secondary to S haematobium infection.
Mortality/Morbidity
In 2004, an estimated 60,200 new patients were diagnosed with bladder cancer in the United States, and 12,700 of those patients died from the disease.
Race
Bladder cancer is more common in whites than in blacks; however, blacks have a worse prognosis than whites.
Sex
The male-to-female ratio is 3:1. Women generally have a worse prognosis than men.
Age
The median age at diagnosis is 68 years, and the incidence increases with age.
Clinical
History
- Approximately 80-90% of patients with bladder cancer present with painless gross hematuria, which is the classic presentation. Consider all patients with gross hematuria to have bladder cancer until proven otherwise. Suspect bladder cancer if any patient presents with unexplained microscopic hematuria.
- Twenty to thirty percent of patients with bladder cancer experience irritative bladder symptoms such as dysuria, urgency, or frequency of urination that are related to more advanced muscle-invasive disease or CIS.
- Patients with advanced disease can present with pelvic or bony pain, lower-extremity edema from iliac vessel compression, or flank pain from ureteral obstruction.
Physical
- Superficial bladder cancer is rarely found during a physical examination.
- Occasionally, an abdominal or pelvic mass may be palpable.
- Examine for lymphadenopathy.
Causes
Up to 80% of bladder cancer cases are associated with environmental exposure, which suggests that bladder cancer is potentially preventable. Smoking is the most commonly associated risk factor and accounts for approximately 50% of all bladder cancers. Nitrosamine, 2-naphthylamine, and 4-aminobiphenyl are possible carcinogenic agents found in cigarette smoke. Bladder cancer is also associated with industrial exposure to aromatic amines in dyes, paints, solvents, leather dust, inks, combustion products, rubber, and textiles. Therefore, higher-risk occupations associated with bladder cancer include painting, driving trucks, and working with metal.
Several medical risk factors are associated with bladder cancer. Patients with prior exposure to radiation treatment of the pelvis have an increased risk of bladder cancer. Chemotherapy with cyclophosphamide increases the risk of bladder cancer via exposure to acrolein, a urinary metabolite of cyclophosphamide. Patients with spinal cord injuries who have long-term indwelling catheters have a 16- to 20-fold increased risk of developing SCC of the bladder.
Coffee consumption does not increase the risk of developing bladder cancer. Early studies of rodents and a minority of human studies suggested a weak connection between artificial sweeteners (eg, saccharin, cyclamate) and bladder cancer; however, most recent studies show no significant correlation.
Although no convincing evidence exists for a hereditary factor in the development of bladder cancer, familial clusters of bladder cancer have been reported. Several genetic mutations have been identified in bladder cancer. Mutations of the tumor suppressor gene for p53, found on chromosome 17, are associated with high-grade bladder cancer and CIS. Mutations of the tumor suppressor gene for p15 and p16, found on chromosome 9, are associated with low-grade and superficial tumors. Retinoblastoma (Rb) tumor suppressor gene mutations are also noted. Bladder cancer is associated with increased expression of the epidermal growth factor gene and the erb- b2 oncogene, and mutations of the oncogenes p21 ras, c-myc, and c-jun.
More on Bladder Cancer |
 Overview: Bladder Cancer |
| Differential Diagnoses & Workup: Bladder Cancer |
| Treatment & Medication: Bladder Cancer |
| Follow-up: Bladder Cancer |
| Multimedia: Bladder Cancer |
| References |
| Further Reading |
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Keywords
urothelial cancer, transitional cell cancer, transitional cell carcinoma, TCC, bladder cancer, bladder tumor, leiomyosarcoma, rhabdomyosarcoma, hematuria, urothelial tumors, carcinoma in situ, CIS, squamous cell carcinoma, SCC, urothelial carcinoma, indwelling Foley catheter, bladder stones, Schistosoma haematobium, S haematobium, primary bladder lymphoma, smoking, aromatic amines, radiation treatment of the pelvis, nitrosamine, 2-naphthylamine, 4-aminobiphenyl, chemotherapy with cyclophosphamide, acrolein, muscle-invasive bladder cancer, urinary tract infection, superficial transitional cell carcinoma, superficial TCC
