A malignant tumor growth within the bladder. Bladder cancers usually arise from the transitional cells of the bladder (the cells lining the bladder).

These tumors may be classified based on their growth pattern as either papillary tumors (meaning they have a wart-like lesion attached to a stalk) or nonpapillary tumors. Nonpapillary tumors are much less common, but they are more invasive and have a poorer prognosis.

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

Cigarette smoking has been shown to increase the risk of developing bladder cancer by a factor of nearly five, compared to non-smokers. As many as 50% of all bladder cancer in men and 30% in women may be attributable to cigarette smoke. This risk, however, does show a gradual decline in individuals who quit smoking.

Studies show that one in four cases of bladder cancer can be attributed to occupational exposure to known carcinogens. Arylamines are a group of chemicals which are responsible for most occupational exposures. Dye workers, rubber workers, aluminum workers, leather workers, truck drivers, and pesticide applicators are at the highest risk; however, the presence of arylamines has been reduced or eliminated in many settings. The association between artificial sweeteners and bladder cancer has been studied and is weak or non-existent.

Women who received radiation therapy for the treatment of cervical cancer have an increased risk of developing transitional cell bladder cancer, as do some people who received the chemotherapy drug, cyclophosphamide (Cytoxan).

Chronic (long term) bladder infection or irritation may lead to the development of squamous cell bladder cancer, however, this cancer is very slow growing. Bladder infections do not predispose to transitional cell cancers.

In third world countries, infection with a parasite (schistosomiasis) has been linked to the development of bladder cancer.

Bladder cancers are classified or staged based on their aggressiveness and the degree that they are different from the surrounding bladder tissue (differentiation). There are several different ways to stage tumors; recently the TNM staging system has become more common. This staging system contains several substages, but it basically categorizes tumors using the following scale:

Bladder cancer is divided into five stages:

• 0 Carcinoma in-situ or non-invasive lesions limited to the bladder mucosa (lining)
• I Tumor extends through the mucosa, but does not extend into the muscle layer
• II Tumor invades into the muscle layer
• III Tumor invades past the muscle layer into tissue surrounding the bladder
• IV Cancer has spread to regional lymph nodes or to distant sites (metastatic)

Bladder cancer spreads by extending into the nearby organs, including the prostate, uterus, vagina, ureters, and rectum. Metastasis can occur to the pelvic lymph nodes or to other parts of the body such as the liver, lungs and bones.

Please note that while most of the symptoms listed below can be associated with bladder cancer, they can also be associated with non-cancerous conditions. Nevertheless, medical evaluation is imperative.

• Hematuria (blood in the urine)
• Urinary frequency
• Painful urination
• Urinary urgency

Additional symptoms that may be associated with this disease:

• Urinary incontinence
• Bone pain or tenderness
• Abdominal pain
• Anemia
• Weight loss
• Lethargy (tiredness)

Physical examination will be performed, including a rectal and pelvic exam.

Diagnostic tests that may be performed include:

• Urinalysis
• Urine cytology (microscopic exam of urine to look for cancerous cells)
• Cystoscopy (use of lighted instrument to view inside of bladder)
• Bladder biopsy (usually performed during cystoscopy)
• Intravenous pyelogram - IVP (to evaluate upper urinary tract for tumors or blockage)

The choice of an appropriate treatment is based on the stage of the tumor, the severity of the symptoms, and the presence of other medical conditions. Generally, superficial tumors (stages 0 and I) are treated by removing the lesion (without removal of the rest of the bladder) and by sometimes administering local (directly into the bladder) chemotherapy. However, because the risk of recurrence is so high (70 -100%), people with bladder cancer require constant follow-up for the rest of their lives.

The treatment for stage II bladder tumors may involve removal of the tumor and a trial of BCG immunotherapy (see below) with serial follow-up. However, most people with stage II and those with stage III tumors will require bladder removal (radical cystectomy). In some patients with stage III tumors who opt not to have surgery or who cannot tolerate surgery, a combination of chemotherapy and radiation may be appropriate. Most patients with stage IV tumors cannot be cured and surgery is not indicated. In these patients, chemotherapy is often considered.

MEDICATIONS:

• CHEMOTHERAPY:

Chemotherapy for the treatment of bladder cancer can be administered through the vein or into the bladder. Chemotherapy is usually given by vein to treat patients with stage IV bladder cancer. Alternatively, chemotherapy may also be given to patients with stage II and stage III cancer after surgery in an attempt to prevent recurrence of the tumor. Chemotherapy may be given as a single agent or in different combinations. These include:

• methotrexate
• vinblastine
• doxorubicin
• cyclophosphamide
• paclitaxel
• carboplatin
• cisplatin
• ifosfamide
• gemcitabine

The combination of two of these drugs, gemcitabine and cisplatin, have recently been shown to be as effective and with less side effects as an older regimen known as MVAC (methotrexate, vinblastine, doxorubicin and cisplatin) and in many centers has replaced MVAC. The combination of paclitaxel and carboplatin has also been effective and is frequently used.

A Foley catheter can be used to instill the medication directly into the bladder (intravesical chemotherapy) in patients with stage I disease. The catheter is removed immediately after the medication has been instilled, though you are instructed to try to hold the medication in your bladder for at least two hours after treatment. Additionally, you may be asked to rotate from side to side every 15 - 30 minutes to ensure complete exposure of the entire bladder wall to the medication.

Several different types of medications may be used for intravesical chemotherapy, such as:

• Thiotepa
• Mitomycin-C
• Doxorubicin (Adriamycin)

Common side effects include bladder wall irritation and pain when urinating. Choice of a specific agent is usually based on the stage of the tumor.

• IMMUNOTHERAPY:

Additionally, bladder cancers are often treated by what is known as intravesical immunotherapy, in which a medication is given that causes your own immune system to attack and kill the tumor cells. Immunotherapy is usually performed using Bacille Calmette-Guerin (commonly known as BCG), which is a solution of genetically altered tubercular bacteria that has been rendered avirulent (not able to produce infection). This medication is administered through a Foley catheter to instill the medication directly into the bladder. Since BCG is a biological agent, special precautions must be taken.

Potential side effects, which include bladder irritability, urinary frequency, urinary urgency, and painful urination are reported by 90% of the people treated with BCG. However, the symptoms usually resolve within a few days after treatment. Other rare side effects include hematuria (blood in the urine), malaise, nausea, chills, joint pain, and itching. Rarely, a systemic tubercular (TB) infection can develop if the TB used does not remain avirulent, requiring treatment with anti-tuberculosis medication. Systemic infection is suspected if you develop an elevated temperature that lasts for more than one day.

SURGERY:

• TRANSURETHRAL RESECTION OF THE BLADDER (TURB):

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

• BLADDER REMOVAL:

Most people with stage II or III bladder cancer will opt for bladder removal (radical cystectomy). Partial bladder removal may be performed if there is only a single lesion with no signs of metastasis. However, only about 10% of the people with bladder cancer meet this criterion.

Radical cystectomy in men usually involves removal of the bladder, prostate, and seminal vesicles. In women, the urethra, uterus, and the anterior (front) vaginal wall are removed along with the bladder. Often, the pelvic lymph nodes are also removed during the surgery for pathological examination. About half of the people treated with radical cystectomy will be completely cured; the other half shows signs of metastasis at the time of the surgery.

A urinary diversion surgery (a surgical procedure to create an alternate method for urine storage) is usually performed with the radical cystectomy procedure. 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 and the other end is brought out through an opening in the skin to create a stoma. The stoma allows the patient to drain the collected urine out of the reservoir.
• People who have had an ileal conduit will need to wear an external urine collection appliance at all times. Possible complications associated with ileal conduit surgery include: bowel obstruction, blood clots, urinary tract infection, pneumonia, skin breakdown around the stoma (the opening in the skin connecting to the ileal conduit), and long-term damage to the upper urinary tract.

CONTINENT URINARY RESERVOIR:

• A continent urinary reservoir is another method of creating a urinary diversion. In this method, a segment of colon is removed and used to create an internal pouch to store urine. This segment of bowel is specially prepared to prevent reflux of urine back up into the ureters and kidneys, and also to reduce the risk of involuntary loss of urine. Patients are able to insert a catheter periodically to drain the urine. A small stoma is placed flush to the skin. Possible complications include: bowel obstruction, blood clots, pneumonia, urinary tract infection, skin breakdown around the stoma, ureteral reflux, and ureteral obstruction.

CURRENT RESEARCH:

Clinical tests are currently underway to evaluate the use of photodynamic therapy in bladder cancer treatment. Photodynamic therapy involves using photosensitizing agents and laser light to detect and kill cancer cells. Other studies are looking at new chemotherapy agents that may be more effective.

MONITORING:

You will be closely monitored for progression of the disease regardless of the type of bladder cancer treatment you received. Monitoring may include:

• Cystoscope evaluations every 3 to 6 months after initial treatment for persons with stage I disease.
• Periodic urine cytology evaluations for patients whose bladders have not been removed.
• Bone scan and/or CT scan to evaluate for metastasis.
• Complete blood count (CBC) to monitor for signs and symptoms of anemia indicating disease progression.
• Monitor for other signs and symptoms indicating disease progression, such as fatigue, weight loss, increased pain, decreased bowel and bladder function, and weakness.

Call your health care provider if you have blood in your urine, or other symptoms of bladder cancer, including urinary urgency, urinary frequency, or painful urination.

Also, call your health care provider for an appointment to be examined if you are over 40 years of age, you are a smoker, or you work in an area of high industrial exposure to potential carcinogens.