Bladder cancer is a cancerous tumor in the bladder -- the organ that holds urine.

In the United States, bladder cancers usually start from the cells lining the bladder (transitional cells).

These tumors may be classified based on the way they grow:

• Papillary tumors have a wart-like appearance and are attached to a stalk.
• Nonpapillary tumors are much less common. However, they are more invasive and have a worse outcome.

As with most other cancers, the exact cause of bladder cancer is uncertain. However, several factors may contribute to its development:

• Cigarette smoking. Smoking increases the risk of developing bladder cancer nearly fivefold. As many as 50% of all bladder cancers in men and 30% in women may be caused by cigarette smoke. People who quit smoking have a gradual decline in risk.
• Chemical exposure at work. About one in four cases of bladder cancer is caused by exposure to cancer-causing chemicals (carcinogens) on the job. Dye workers, rubber workers, aluminum workers, leather workers, truck drivers, and pesticide applicators are at the highest risk. Arylamines are the chemicals most responsible. However, arylamines have been reduced or eliminated in many workplaces.
• Radiation and chemotherapy. Women who received radiation therapy for the treatment of cervical cancer have an increased risk of developing transitional cell bladder cancer. Some people who have received the chemotherapy drug cyclophosphamide (Cytoxan) are also at increased risk.
• Bladder infection. A long-term (chronic) bladder infection or irritation may lead to the development of squamous cell bladder cancer. Bladder infections do not increase the risk of transitional cell cancers.
• Parasite infection. In third world countries, infection with the schistosomiasis parasite has been linked to the development of bladder cancer.

The association between artificial sweeteners and bladder cancer has been studied and is weak or nonexistent.

Bladder cancers are classified, or staged, based on their aggressiveness and how much they differ from the surrounding bladder tissue. There are several different ways to stage tumors. Recently, the TNM (Tumor, Nodes, Metastasis) staging system has become common. This staging system categorizes tumors using the following scale:

• Stage 0 -- Non-invasive tumors that are only in the bladder lining
• Stage I -- Tumor goes through the bladder lining, but does not reach the muscle layer of the bladder
• Stage II -- Tumor goes into the muscle layer of the bladder
• Stage III -- Tumor goes past the muscle layer into tissue surrounding the bladder
• Stage IV -- Tumor has spread to neighboring lymph nodes or to distant sites (metastatic disease)

Bladder cancer spreads by extending into the nearby organs, including the:

• Prostate
• Rectum
• Ureters
• Uterus
• Vagina

It can also spread to lymph nodes in the pelvis, or to other parts of the body, such as:

• Bones
• Liver
• Lungs

Most of the symptoms of bladder cancer can also occur with non-cancerous conditions. It's important to get evaluated if you have any of these symptoms:

• Blood in the urine
• Painful urination
• Urinary frequency
• Urinary urgency

Other symptoms that can occur with this disease:

• Abdominal pain
• Anemia
• Bone pain or tenderness
• Lethargy and fatigue
• Urinary incontinence
• Weight loss

The health care provider will perform a physical examination, including a rectal and pelvic exam.

Diagnostic tests that may be done include:

• Abdominal CT scan
• Bladder biopsy (usually performed during cystoscopy)
• Cystoscopy (examining the inside of the bladder with a camera)
• Intravenous pyelogram - IVP
• Urinalysis
• Urine cytology

The choice of treatment depends on the stage of the tumor, the severity of the symptoms, and the presence of other medical conditions.

Stage 0 and I treatments:

• Surgery to remove the tumor without removing the rest of the bladder
• Chemotherapy or immunotherapy directly into the bladder

Stage II and III treatments:

• Surgery to remove the entire bladder (radical cystectomy)
• Surgery to remove only part of the bladder, followed by radiation and chemotherapy
• Chemotherapy to shrink the tumor before surgery
• A combination of chemotherapy and radiation (in patients who choose not to have surgery or who cannot have surgery)

Most patients with stage IV tumors cannot be cured and surgery is not appropriate. In these patients, chemotherapy is often considered.

CHEMOTHERAPY

Chemotherapy may be given to patients with stage II and III disease either before or after surgery to help prevent the tumor from returning.

Chemotherapy may be given as a single drug or in different combinations of drugs. These drugs include:

• Carboplatin
• Cisplatin
• Cyclophosphamide
• Docetaxel
• Doxorubicin
• Gemcitabine
• Ifosfamide
• Methotrexate
• Paclitaxel
• Vinblastine

The combination of gemcitabine and cisplatin is as effective as an older treatment called MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) with fewer side effects. Many centers have replaced MVAC with this new combination. Paclitaxel and carboplatin is another effective combination that is frequently used.

For early disease (stages 0 and I), chemotherapy is usually given directly into the bladder. Several different types of chemotherapy medications may be delivered directly into the bladder. They include:

• Doxorubicin (Adriamycin)
• Mitomycin-C (Mutamycin)
• Thiotepa (Thioplex)

A Foley catheter can be used to deliver the medication into the bladder. Common side effects include bladder wall irritation and pain when urinating. For more advanced stages (II-IV), chemotherapy is usually given by vein (intravenously).

IMMUNOTHERAPY

Bladder cancers are often treated by immunotherapy. In this treatment, a medication causes your own immune system to attack and kill the tumor cells. Immunotherapy for bladder cancer is usually performed using the Bacille Calmette-Guerin vaccine (commonly known as BCG). It is given through a Foley catheter directly into the bladder.

Possible side effects include:

• Frequent urination
• Irritable bladder
• Painful urination
• Urgent need to urinate

These symptoms usually improve within a few days after treatment. Rare side effects include:

• Blood in the urine
• Chills
• Itching
• Joint pain
• Malaise
• Nausea

Rarely, a tuberculosis-like infection can develop. This requires treatment with an anti-tuberculosis medication.

TRANSURETHRAL RESECTION OF THE BLADDER (TURB)

People with stage 0 or I bladder cancer can be treated with transurethral resection of the bladder (TURB). This surgical procedure is performed under general or spinal anesthesia. A cutting instrument is inserted through the urethra to remove the bladder tumor.

BLADDER REMOVAL

Many people with stage II or III bladder cancer may need to have their bladder removed (radical cystectomy). Partial bladder removal may be performed in some patients. Removal of part of the bladder is usually followed by radiation therapy and chemotherapy to help decrease the chances of the cancer returning. Patients who have the entire bladder removed will receive chemotherapy after surgery to decrease the risk of the cancer coming back.

Radical cystectomy in men usually involves removing the bladder, prostate, and seminal vesicles. In women, the urethra, uterus, and the front wall of the vagina are removed along with the bladder. Often, the pelvic lymph nodes are also removed during the surgery to be examined in the laboratory.

A urinary diversion surgery (a surgical procedure to create an alternate method for urine storage) is usually done with radical cystectomy. Two common types of urinary diversion are an ileal conduit and a continent urinary reservoir.

ILEAL CONDUIT

An ileal conduit is a small urine reservoir that is surgically created from a small segment of bowel. The ureters that drain urine from the kidneys are attached to one end of the bowel segment. The other end is brought out through an opening in the skin (a stoma). The stoma allows the patient to drain the collected urine out of the reservoir.

People who have had an ileal conduit need to wear a urine collection appliance outside their body at all times. Possible complications with ileal conduit surgery include:

• Bowel obstruction
• Blood clots
• Long-term damage to the upper urinary tract
• Pneumonia
• Skin breakdown around the stoma
• Urinary tract infection

CONTINENT URINARY RESERVOIR

A continent urinary reservoir is an alternate method of storing urine. A segment of colon is removed. It is used to create an internal pouch to store urine.

Patients are able to insert a catheter periodically to drain the urine. A small stoma is placed against the skin.

Possible complications include:

• Blood clots
• Bowel obstruction
• Pneumonia
• Skin breakdown around the stoma
• Ureteral obstruction
• Ureteral reflux
• Urinary tract infection

ORTHOTOPIC NEOBLADDER

This surgery is becoming more common in patients undergoing cystectomy. A segment of bowel is folded over to make a pouch (a neobladder, which means "new bladder"). Then it is attached to the place in the urethra where the urine normally empties from the bladder.

This procedure allows patients to maintain some normal urinary control. However, there are complications (including urine leakage at night). Urination is usually not the same as it was before surgery.

Some patients may not be good candidates for this procedure. Discuss the pros and cons with your urologist.

Patients are closely monitored to see whether the disease gets worse, regardless of which kind of treatment they received. Monitoring may include:

• Bone scan and/or CT scan to check for cancer spread
• Checking for other signs of disease progression, such as fatigue, weight loss, increased pain, decreased bowel and bladder function, and weakness
• Complete blood count (CBC) to monitor for anemia
• Cystoscope evaluations every 3 to 6 months after treatment
  • Urine cytology evaluations (for people whose bladder has not been removed)

How well a patient does depends on the initial stage and response to treatment of the bladder cancer. The outlook for stage 0 or I cancers is fairly good. Although the risk of the cancer returning is high, most bladder cancers that return can be surgically removed and cured.

The cure rates for people with stage III tumors are less than 50%. Patients with stage IV bladder cancer are rarely cured.

Bladder cancers may spread into the nearby organs. They may also travel through the pelvic lymph nodes and spread to the liver, lungs, and bones. Additional complications of bladder cancer include:

• Anemia
• Swelling of the ureters (hydronephrosis)
• Urethral stricture
• Urinary incontinence

Call your health care provider if you have blood in your urine or other symptoms of bladder cancer, including:

• Frequent urination
• Painful urination
• Urgent need to urinate

Also, call your health care provider for an appointment if:

• You are exposed to possible cancer-causing chemicals at work
• You smoke

Quitting cigarette smoking and eliminating environmental hazards will reduce your risk of developing bladder cancer.

Bajorin D. Tumors of the kidney, bladder, ureters, and renal pelvis. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia , Pa : Saunders Elsevier; 2007: chap 207.

National Comprehensive Cancer Network. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology: Bladder Cancer, Including Upper Tract Tumors and Urothelial Carcinoma of the Prostate. 2009. Version 1.2009.