The bladder is an organ located in the pelvic cavity that stores and discharges urine. Urine is produced by the kidneys, carried to the bladder by the ureters, and discharged from the bladder through the urethra. Bladder cancer accounts for approximately 90% of cancers of the urinary tract (renal pelvis, ureters, bladder, urethra).

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Bladder cancer usually originates in the bladder lining, which consists of a mucous layer of transitional epithelial cells (surface cells that expand and deflate), smooth muscle, and a fibrous layer. Tumors are categorized as low stage (superficial) or high stage (muscle invasive).

In industrialized countries (e.g., United States, Canada, France), more than 90% of cases originate in the transitional epithelial cells (called transitional cell carcinoma; TCC). In developing countries, 75% of cases are squamous cell carcinomas caused by Schistosoma haematobium (parasitic organism) infection. Rare types of bladder cancer include small cell carcinoma, carcinosarcoma, primary lymphoma, and sarcoma.

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According to the National Cancer Institute, the highest incidence of bladder cancer occurs in industrialized countries such as the United States, Canada, and France. Incidence is lowest in Asia and South America, where it is about 70% lower than in the United States.

Incidence of bladder cancer increases with age. People over the age of 70 develop the disease 2 to 3 times more often than those aged 55–69 and 15 to 20 times more often than those aged 30–54.

Bladder cancer is 2 to 3 times more common in men. In the United States, approximately 38,000 men and 15,000 women are diagnosed with the disease each year. Bladder cancer is the fourth most common type of cancer in men and the eighth most common type in women. The disease is more prevalent in Caucasians than in African Americans and Hispanics.

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Cancer-causing agents (carcinogens) in the urine may lead to the development of bladder cancer. Cigarette smoking contributes to more than 50% of cases, and smoking cigars or pipes also increases the risk. Other risk factors include the following:

• Age Chronic bladder inflammation (recurrent urinary tract infections, urinary stones)
• Consumption of Aristolochia fangchi (herb used in some weight-loss formulas)
• Diet high in saturated fat
• Exposure to second-hand smoke
• External beam radiation
• Family history of bladder cancer (several genetic risk factors identified)
• Gender (male) Infection with Schistosoma haematobium (parasite found in many developing countries)
• Personal history of bladder cancer Race (Caucasian)
• Treatment with certain drugs (e.g., cyclophosfamide—used to treat cancer)

Exposure to carcinogens in the workplace also increases the risk for bladder cancer. Medical workers exposed during the preparation, storage, administration, or disposal of antineoplastic drugs (used in chemotherapy) are at increased risk. Occupational risk factors include recurrent and early exposure to hair dye, and exposure to dye containing aniline, a chemical used in medical and industrial dyes. Workers at increased risk include the following: Hairdressers Machinists Printers Painters Truck drivers Workers in rubber, chemical, textile, metal, and leather industries.

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The primary symptom of bladder cancer is blood in the urine (hematuria). Hematuria may be gross (visible to the naked eye) or microscopic (visible only under a microscope) and is usually painless. Other symptoms include frequent urination and pain upon urination (dysuria).

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Diagnosis of bladder cancer includes urological tests and imaging tests. A complete medical history is used to identify potential risk factors (e.g., smoking, exposure to dyes). Laboratory tests may include the following: Urinalysis (to detect microscopic hematuria) Urine cytology (to detect cancer cells by examining cells flushed from the bladder during urination) Urine culture (to rule out urinary tract infection) Various imaging tests may also be performed. Intravenous pyelogram (IVP) is the standard imaging test for bladder cancer. In this procedure, a contrast agent (radiopaque dye) is administered intravenously and x-rays are taken as the dye moves through the urinary tract. IVP provides information about the structure and function of the kidneys, ureters, and bladder. Other imaging tests include CT scan, MRI scan, bone scan, and ultrasound. If bladder cancer is suspected, cystoscopy and biopsy are performed. Local anesthesia is administered and a cystoscope (thin, telescope-like tube with a tiny camera attached) is inserted into the bladder through the urethra to allow the physician to detect abnormalities. In biopsy, tissue samples are taken from the lesion(s) and examined for cancer cells. If the sample is positive, the cancer is staged using the tumor, node, metastases (TNM) system.

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Treatment for bladder cancer depends on the stage of the disease, the type of cancer, and the patient’s age and overall health. Options include surgery, chemotherapy, radiation, and immunotherapy. Treatments are sometimes combined (e.g., surgery or radiation and chemotherapy).

Surgery
The type of surgery depends on the stage of the disease. In early bladder cancer, the tumor may be resected (removed) using instruments inserted through the urethra (transurethral resection). In advanced stages of the disease, partial or radical cystectomy (removal of the bladder) is performed. Radical cystectomy includes removal of nearby lymph nodes. In men, the prostate gland is also removed. In women, the uterus, ovaries, fallopian tubes, and a section of the vagina may be removed as well. Radical cystectomy requires a urostomy, an opening in the abdomen created for the discharge of urine. Complications include infection, urinary stones, and urine blockages.

Immunotherapy
Immunotherapy, also called biological therapy, is used to enhance the immune system’s ability to fight cancer. In this treatment, BCG, a vaccine derived from the bacteria that causes tuberculosis, is infused through the urethra into the bladder, once a week for 6 weeks. This vaccine stimulates the immune system to destroy cancer cells and is used in early bladder cancer that is superficial. Sometimes BCG is used with interferon.

Side effects include inflammation of the bladder (cystitis), inflammation of the prostate (prostatitis), and flu-like symptoms. If high fever (over 101.5 °F) occurs, it may indicate that the bacteria have entered the bloodstream (i.e., bacteremia), a life-threatening condition that requires antibiotic treatment. Immunotherapy is not used in patients with gross hematuria.

Chemotherapy
Chemotherapy is the use of drugs to destroy cancer cells. It is a systemic treatment (i.e., destroys cancer cells throughout the body) and is administered orally or intravenously (through a vein). In early bladder cancer, intravesical chemotherapy (infused into the bladder through the urethra) may be recommended. Chemotherapy may be neoadjuvant (before surgery) or adjuvant (after surgery) therapy.

Drugs used in the treatment of bladder cancer include valrubicin (Valstar™), thiotepa (Thioplex®), mitomycin, and doxorubicin (Rubex®). Side effects can be severe and include the following:

• Abdominal pain
• Anemia
• Bladder irritation
• Blurred vision
• Excessive bleeding or bruising
• Fatigue
• Headache
• Infection
• Loss of appetite Nausea and vomiting
• Weakness

Radiation
Radiation uses high-energy x-rays to destroy cancer cells. External beam radiation is emitted from a machine outside the body and internal radiation is emitted from radioactive "seeds" implanted into the tumor. Either type of radiation therapy may be used after surgery to destroy cancer cells that may remain. Radiation therapy is also used to ease symptoms in advanced cases of bladder cancer. Side effects include inflammation of the rectum (proctitis), incontinence, skin irritation, hematuria, fibrosis (buildup of fibrous tissue), and impotence.

Photodynamic therapy is a new treatment for early bladder cancer. It involves administering drugs to make cancer cells more sensitive to light and then shining a special light onto the bladder. This treatment is being studied in clinical trials.

Follow-Up
Bladder cancer has a high rate of recurrence. Urine cytology and cystoscopy are performed every 3 months for 2 years, every 6 months for the next 2 years, and then yearly.

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Superficial bladder cancer has a 5-year survival rate of about 85%. Invasive bladder cancer has a less favorable prognosis. Approximately 5% of patients with metastasized bladder cancer live 2 years after diagnosis. Cases of recurrent bladder cancer indicate an aggressive tumor and a poor prognosis.

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Bladder cancer cannot be prevented. The best way to lower the risk is not to smoke. Studies have shown that drinking plenty of fluids daily also lowers the risk for bladder cancer.

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