Key Terms: Biopsy, Chemotherapy, Computed tomography (CT) scan, Cystoscopy, Electrofulguration, Immunotoxins, Intravenous pyelogram, Magnetic resonance imaging, Partial cystectomy, Photodynamic therapy, Radiation therapy, Radical cystectomy, Stoma, Transurethral resection.
Definition
Bladder cancer is a disease in which the cells lining the urinary bladder lose the ability to regulate their growth and start dividing uncontrollably. This abnormal growth results in a mass of cells that form a tumor.
Description
The urinary bladder is a hollow muscular organ that stores urine from the kidneys until it is excreted out of the body. Two tubes called the ureters bring the urine from the kidneys to the bladder. The urethra carries the urine from the bladder to the outside of the body.
Bladder cancer has a very high rate of recurrence following treatment. Even after superficial tumors are completely removed, there is a 75% chance that new tumors will develop in other areas of the bladder. Patients need very frequent and thorough follow-up care. When detected at the early stages, the prognosis for bladder cancer is excellent. At least 94% of patients survive five years or more after initial diagnosis. If the disease has spread to the nearby tissues, however, the survival rates drop to 49%. If it has metastasized to distant organs such as the lung or liver, only 6% of patients will survive five years or more.
Demographics
Bladder cancer is the sixth most common cancer in the United States. The American Cancer Society (ACS) estimated that in 2001, approximately 54,300 new cases of bladder cancer would be diagnosed (about 39,200 men and 15,100 women), causing approximately 12,400 deaths.
The highest occurrences of bladder cancer are found in industrialized countries such as the United States, Canada, France, Denmark, Italy, and Spain. In all countries, the incidence of bladder cancer is higher for men than women. Among men, the highest rates occur in white non-Hispanic males (33.1 per 100,000). The rates for men of African descent and Hispanic men are similar and are approximately one-half of the rate among white non-Hispanic men. The lowest rate of bladder cancer occurs in the Asian population. Among women, the highest rates also occur in white non-Hispanic females and are approximately twice the rate for Hispanics. Women of African descent have higher rates of bladder cancer than Hispanic women.
Age is also an important factor: bladder cancer is significantly more common in older men and women in all populations. Bladder cancer rates for people aged 70 years and older are two to three times higher than for people in the 55 to 69 age group, and approximately 15 to 20 times higher than for people between the ages of 30 and 54.
Causes and Symptoms
Although the exact cause of bladder cancer is not known, smokers are twice as likely to get the disease as are nonsmokers. Smoking is subsequently considered to be the greatest risk factor for bladder cancer. Workers who are exposed to certain chemicals that are used in the dye, rubber, leather, textile, and paint industries are also believed to be at a higher risk for bladder cancer.
Frequent urinary infections, kidney and bladder stones, and other conditions that cause long-term irritation to the bladder may increase the risk of getting bladder cancer. A past history of tumors in the bladder also increases one's risk of developing new tumors.
One of the first warning signals of bladder cancer is blood in the urine. There may be enough blood in the urine to change its color to a yellow-red or dark red. At other times, the color of the urine appears normal but chemical testing of the urine reveals the presence of blood cells. Painful urination, increased frequency, and increased urgency (the sensation of having to urinate immediately but being unable to do so) are other possible signs of bladder cancer. All of these symptoms may also be caused by conditions other than cancer, so it is important to see a doctor to have the symptoms evaluated.
In 2003, studies showed that hormone replacement therapy (HRT), a treatment used by many postmenopausal women, significantly increased the risk of bladder and other cancers.
Diagnosis
If a doctor has any reason to suspect bladder cancer, several tests may be used to find out if the disease is present. A complete medical history will be taken to check for any risk factors. A thorough physical examination will be conducted to assess all the signs and symptoms. Laboratory testing of a urine sample will help to rule out the presence of a bacterial infection. In a urine cytology test, the urine is examined under a microscope to look for any abnormal or cancerous cells. A catheter (tube) can be advanced into the bladder through the urethra and a salt solution passed through it to wash the bladder. The solution can then be collected and examined under a microscope to check for the presence of any cancerous cells.
A test known as the intravenous pyelogram (IVP) is an x-ray examination performed after a dye is injected into a vein in the arm. The dye travels through the blood stream and reaches the kidneys to be excreted, clearly outlining the kidneys, ureters, bladder, and urethra. Multiple x rays are taken to detect any abnormalities in the lining of these organs.
The physician may use a procedure known as a cystoscopy to view the inside of the bladder. A thin hollow lighted tube is introduced into the bladder through the urethra. If any suspicious-looking masses are seen, a small piece of the tissue can be painlessly removed using a pair of biopsy forceps. The tissue is then examined microscopically to verify if cancer is present, and if so, the type of cancer will be identified.
If cancer is detected and there is evidence showing that it has metastasized to distant sites in the body, imaging tests such as chest x rays, computed tomography (CT) scans, and magnetic resonance imaging (MRI) may be done to determine which organs are affected. Bladder cancer tends to spread to the lungs, liver, and bone.
Treatment Team
Treatment for bladder cancer depends on the stage of the disease and how deeply the cancer has penetrated the bladder wall. It also depends on the grade of the cancer and on the patient's general health status and personal preferences. Most likely, a team of specialists including a urologist, an oncologist, a surgeon, and a radiation oncologist will be responsible for treatment. The treatment team will develop a plan tailored to the individual patient and may recommend one treatment method or a combination of methods.
Clinical Staging, Treatments, and Prognosis
Staging
The following stages are used by health care providers to classify the location, size, and spread of the cancer, according to the TNM (tumor, lymph node, and metastases) staging system:
- Stage 0: Cancer is found only on the inner lining of the bladder (a noninvasive carcinoma).
- Stage I: Cancer has spread to the layer of tissue beyond the inner lining of the bladder but not to the bladder muscles.
- Stage II: Cancer has spread to the muscles in the bladder wall but not to the fatty tissue surrounding the bladder.
- Stage III: Cancer has spread to the fatty tissue surrounding the bladder and potentially to the prostate, vagina, or uterus, but not to the lymph nodes or other organs.
- Stage IV: Cancer has spread to the lymph nodes, pelvic or abdominal wall, and/or other organs.
- Recurrent: Cancer has recurred in the bladder or at another site after having been treated.
Standard Treatments
The three standard modes of treatment that are available for bladder cancer are surgery, radiation therapy, and chemotherapy.
Surgery is considered to be an option only when the disease is in its early stages. If the tumor is localized to a small area and has not spread to the outer layers of the bladder, then the surgery is done without entering the abdomen. A cystoscope is introduced into the bladder through the urethra, and the tumor is removed. This procedure is called a transurethral resection (TUR). Passing a high-energy laser beam through the cystoscope to burn cancer cells, a procedure known as electrofulguration, may treat any remaining cancer.
If the cancer has invaded the wall of the bladder, surgery will be done through an incision in the abdomen.
Cancer that is not very large can be removed by partial cystectomy, a procedure where a part of the bladder is removed. If the cancer is large or is present in more than one area of the bladder, a radical cystectomy is done. The entire bladder is removed in this procedure; adjoining organs may also be removed. In men, the prostate is removed, while in women, the uterus, ovaries, and fallopian tubes are removed.
If the entire urinary bladder is removed, then an alternate storage place must be created for urine before it is excreted out of the body. To do this, a piece of intestine is converted into a small bag and attached to the ureters. This is connected to an opening (stoma) that is made in the abdominal wall. The procedure is called a urostomy. In some urostomy procedures, the urine from the intestinal sac is routed into a bag that is placed over the stoma in the abdominal wall. The bag is hidden by clothing and has to be emptied occasionally by the patient. In a different procedure, the urine is collected in the intestinal sac, but there is no bag on the outside of the abdomen. The intestinal sac has to be emptied by the patient by placing a drainage tube through the stoma.
Radiation therapy that uses high-energy rays to kill cancer cells is generally used after surgery to destroy any remaining cancer cells. If the tumor is in a location that makes surgery difficult or if it is large, radiation may be used before surgery to shrink the tumor. In cases of advanced bladder cancer, radiation therapy is used to ease the symptoms such as pain, bleeding, or blockage. External beam radiation focuses a beam of radiation on the area of the tumor. Alternatively, a small pellet of radioactive material may be placed directly into the cancer. This is known as interstitial radiation therapy.
Chemotherapy uses anticancer drugs to destroy the cancer cells that may have migrated to distant sites. The drugs are injected into the patient intravenously or taken orally in pill form. Generally a combination of drugs is more effective than any single drug in treating bladder cancer. Chemotherapy may be given following surgery to kill any remaining cancer cells. Called neoadjuvant chemotherapy, this treatment may allow people with bladder cancer to live up to 31 months longer than previous treatments allowed. Chemotherapy also may be given even when no remaining cancer cells can be seen (adjuvant chemotherapy). Anticancer drugs, including thiotepa, doxorubicin, and mitomycin, may also be instilled directly into the bladder (intravesicular chemotherapy) to treat superficial tumors. In 2003, the FDA was giving fast track designation to a form of paclitaxel, a common anticancer drug, that was shown effective in treating metastatic or locally advanced bladder cancer.
Immunotherapy or biological therapy uses the body's own immune cells to fight the disease. To treat superficial bladder cancer, bacillus Calmette-Guérin (BCG) may be instilled directly into the bladder. BCG is a weakened (attenuated) strain of the tuberculosis bacillus that stimulates the body's immune system to fight the cancer. This therapy has been shown to be effective in controlling superficial bladder cancer.
A 2003 report stated that giving patients with bladder cancer chemotherapy followed by surgery may improve their outcomes. In the study of 307 patients, those with this combination of therapy lived two years longer than those treated with surgery only.
Photodynamic treatment is a novel mode of treatment that uses special chemicals and light to kill the cancerous cells when the bladder cancer is in its early stages. First, a drug is introduced into the bladder that makes the cancer cells more susceptible to light. A special light is then shone on the bladder in an attempt to destroy the cancerous cells.
Alternative and Complementary Therapies
Gene therapy is a new method being tested as a complementary therapy for bladder cancer. Research has shown that mutations in tumor suppressor genes can cause abnormal growth of bladder cells. Gene therapy involves infecting bladder cancer cells with specially designed viruses that contain a normal gene in order to restore a normal cell growth process.
Immunotherapy is another area that is expected to contribute new complementary treatment methods. Immunotoxins are antibodies produced in the laboratory that recognize specific substances that are more abundant in cancer cells than in normal cells. Once the immunotoxins identify a cancer cell, they deliver a powerful toxin attached to the antibody that enters and kills the cell.
Coping With Cancer Treatment
As with any cancer, shock and stress are natural reactions to a confirmed bladder cancer diagnosis. Coping is often made easier with access to helpful information and support services. Many patients want to learn all they can about the disease and their treatment choices so as to be fully involved in the decisions that are being made concerning their medical care. National cancer organizations are an important source of medical information. Many associations have also been organized to allow patients the opportunity to meet others undergoing similar experiences in support groups.
Patients are often uncomfortable during the first few days after bladder surgery. They may also experience fatigue and weakness. Those undergoing radiation therapy or chemotherapy may experience side effects such as pain, fatigue, rashes, or bleeding. Pain can be controlled with medication and patients should feel free to discuss aspects of pain relief with their physician or nurse.
Questions to Ask the Doctor
- Why do I need to have a biopsy?
- How long will it take? Will I be awake? Will it hurt?
- How soon will I know the results?
- If I do have bladder cancer, who will talk with me about treatment? When?
Clinical Trials
In 2001 the National Cancer Institute (NCI) supported over 50 bladder cancer clinical trials to evaluate a variety of anticancer drugs. Some trials study new treatments involving radiation therapy, chemotherapy, biological therapies, and new combinations of various therapies. Other trials study ways to lower the side effects of treatment. Patients who take part in these studies often have the chance to benefit from promising new drugs and developments. Those interested in taking part in a trial should discuss the possibility with their physician and consult an NCI booklet entitled, "Taking Part in Clinical Trials: What Cancer Patients Need To Know" (NIH Publication #97-4250).
Prevention
Since it is not known what exactly causes bladder cancer, there is no certain way to prevent its occurrence. Avoiding risk factors whenever possible is the best alternative. Since smoking doubles one's risk of getting bladder cancer, avoiding tobacco may prevent at least half the deaths that result from bladder cancer. Taking appropriate safety precautions when working with organic cancer-causing chemicals is another way of reducing one's risk.
Those with a history of bladder cancer, kidney stones, urinary tract infections, and other conditions that cause long-term irritation to the bladder are advised to undergo regular screening tests such as urine cytology, cystoscopy, and x rays of the urinary tract, so that cancer may be detected at an early stage and treated appropriately.
Special Concerns
Special concerns may arise for those who have undergone partial or radical cystectomy. For example, if the bladder has to be removed, the patient will need to learn a new way to store and pass urine. Women who have had a radical cystectomy are not able to have children because their uterus has also been removed. Men who have had a radical cystectomy will become impotent (unable to sustain an erection) if their prostate and seminal vesicles have also been removed.
Resources
Periodicals
Good, Brian. "Battle Against Bladder Cancer." Men's Health 18 (December 2003): 32.
Grossman, H. Barton, et al. "Neoadjuvant Chemotherapy Plus Cystectomy Compared With Cystectomy Alone for Locally Advanced Bladder Cancer." The New England Journal of Medicine August 28, 2003: 859.
"HRT Increases Risk of Gallbladder, Breast, Endometrial, and Bladder Cancer." Women's Health Weekly July 17, 2003: 31.
Lamm, D. L., and M. Allaway. "Current trends in bladder cancer treatment." Annales Chirurgiae et Gynaecologiae 89 (2000): 234-241.
Lockyer, C. R., and D. A. Gillatt. "BCG immunotherapy for superficial bladder cancer." Journal of the Royal Society of Medicine 94 (March 2001): 119-23.
Oosterlinck, W. "The management of superficial bladder cancer." BJU International 87 (January 2001): 135-40.
Petrovich, Z., G. Jozsef, and L. W. Brady. "Radiotherapy for carcinoma of the bladder: a review." American Journal of Clinical Oncology 24 (February 2001): 1-9.
Ryan, C. W., and N. J. Vogelzang. "Gemcitabine in the treatment of bladder cancer." Expert Opinions in Pharmacotherapy 1 (March 2000): 547-53.
"Tocosol Paclitaxel Receives Expedited Review for Bladder Cancer Indication." Biotech Week November 26, 2003: 443.
Other
"Bladder Cancer." American Cancer Society's Urinary Bladder Cancer Resource Center. 2000. [cited June 26, 2001]. .
"Bladder Cancer: FAQ." American Cancer Society. [cited July 11, 2000 and June 26, 2001]. .
"Staging: Stages of cancer of the bladder." University of Pittsburgh Cancer Institute. June 2001. [cited June 28, 2001]. .
"Taking Part in Clinical Trials: What Cancer Patients Need To Know (NIH Publication #97 4250)." National Institutes of Health & National Cancer Institute. May 1998. [cited June 26, 2001]. .
—Lata Cherath, Ph.D.; Monique Laberge, Ph.D.; Teresa G. Odle
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