Bladder Cancer

Bladder cancer is the fourth most common new cancer in men and the tenth in women. About 60,000 new cases of bladder cancer will be diagnosed this year.

What causes bladder cancer?

No one knows the exact causes of bladder cancer, but research continues to find answers and eventually a cure.

Many studies have found the following risk factors for bladder cancer:

Age.
The chance of getting bladder cancer increases with age-bladder cancer mostly affects people in their 60s and 70s. People under 40 rarely get this disease, but it does happen occassionally.
Cigarette smoking.
Cigarette smoking is directly responsible for most cases of bladder cancer. Smoking causes about half of all bladder cancer deaths in men and about one-third of the bladder cancer deaths in women.
Working in certain industries.
Some workers have a higher risk of getting bladder cancer because of carcinogens (cancer-causing agents) in the workplace. Workers in the rubber, dye, chemical, and leather industries are at increased risk, as are hairdressers, machinists, metal workers, printers, painters, textile workers, and truck drivers.
Race.
Whites get bladder cancer twice as often as African-Americans and Hispanics. The lowest rates are among Asians.
Gender.
Men are three times more likely than women to develop bladder cancer. However, women are more likely to die from the disease because they are sometimes not diagnosed in the early stage.
Family history.
People with family members who have bladder cancer are more likely to get the disease. Researchers are studying changes in certain genes that may increase the risk of bladder cancer.

How does bladder cancer develop?

Nearly 80 percent of bladder cancers remain within the bladder lining, or mucosa. This type of bladder cancer is called superficial bladder cancer, or carcinoma in situ, and often comes back after treatment.

In invasive cases, the cancer extends through the bladder wall and may grow int o other organs and bones, including lymph nodes, reproductive organs, lungs, liver, and the pelvis.

What are the symptoms of bladder cancer?

The most common symptoms of bladder cancer include:

  • Blood in the urine (making the urine slightly rusty to deep red)
  • Pain during urination
  • Frequent urination, or feeling the need to urinate without being able to

Having these symptoms does not necessarily mean a person has bladder cancer. Infections, benign tumors, bladder stones, or other problems also can cause these symptoms. Anyone with these symptoms should see a doctor so that the problem can be caught early.

How is bladder cancer diagnosed?

If a patient has symptoms that suggest bladder cancer, the doctor will give the patient a complete physical exam and order lab tests. The person may have one or more of the following procedures:

Physical exam-
The doctor feels the abdomen and pelvis for tumors. The physical exam may include a rectal or vaginal exam.
Urine tests-
The laboratory checks the urine for blood, cancer cells, and other signs of disease. The most common urine test for bladder cancer is a urine cytology, similar to a PAP smear.
Intravenous pyelogram-
The doctor injects dye into a blood vessel. The dye collects in the urine, making the bladder and kidneys show up on x-rays.
Cystoscopy-
The doctor uses a thin, lighted tube called a cystoscope to look directly into the bladder. The doctor inserts the cystoscope into the bladder through the urethra to examine the lining of the bladder. The patient may need anesthesia for this procedure.

The doctor can remove samples of tissue with the cystoscope. A pathologist then examines the tissue under a microscope. The removal of tissue to look for cancer cells is called a biopsy. In many cases, a biopsy is the only sure way to tell whether cancer is present. For a small number of patients, the doctor removes the entire cancerous area during the biopsy. For these patients, bladder cancer is diagnosed and treated in a single procedure.

Staging

If bladder cancer is diagnosed, the doctor needs to know the stage, or extent, of the disease to plan the best treatment. Staging is a careful attempt to find out whether the cancer has invaded the bladder wall, whether the disease has spread, and if so, to what parts of the body. In a sense it is a measure of depth and extent of the disease.

The doctor may determine the stage of bladder cancer at the time of diagnosis, or may need to give the patient more tests. Such tests may include imaging tests - CT scan, magnetic resonance imaging (MRI), sonogram, intravenous pyelogram, bone scan, or chest x-ray. Sometimes staging is not complete until the patient has surgery.

These are the main features of each stage of the disease:

Stage 0- Cancer cells found only on the surface of the inner lining of the bladder; known as superficial cancer or carcinoma in situ (CIS).

Stage I- Cancer cells found deep in the inner lining of the bladder, but not in the muscle of the bladder. Technically, while "invasive", this still counts as superficial bladder cancer since it can be removed through cystoscope surgery.

Stage II- Cancer cells have spread to the muscle of the bladder.

Stage III- Cancer cells have spread through the muscular wall of the bladder to the layer of tissue surrounding the bladder. At this stage, the cancer may also have spread to the reproductive organs.

Stage IV- Cancer extends to the abdomen or pelvis. At this stage, the cancer may have also spread to the lymph nodes and even as far away as the lungs.

Grading

In addition to knowing the extent of the disease, it is also important to know whether the disease has intrinsic aggressive potential. Under the microscope, the pathologist can usually determine this by looking at the individual cancer cells. Bladder cancer has traditionally been graded on a 3-4 point scale where grade 1 signifies a low-aggressive cancer and grade 3-4 signifies a high-aggressive cancer. Grade 2 is intermediate.

Recently, an attempt has been made by pathologists to adopt a simpler, more unified designation of simply low-grade or high-grade. The grade of the cancer is probably the single most important predictor of prognosis for superficial bladder cancers. Unfortunately, by the time the cancers have reached Stages II-IV, grade is less important since almost all of them are of the high-grade type. By definition, CIS is always high-grade.

Methods of Treatment

There are many different treatments for bladder cancer, such as surgery, radiation therapy, chemotherapy, or immunological therapy.

Surgery
is a common treatment for bladder cancer. The type of surgery depends largely on the stage and grade of the tumor.
Transurethral resection:
The doctor may treat early stage (superficial) bladder cancer with transurethral resection (known as TUR). During TUR, a cystoscope is inserted into the bladder through the urethra. A small wire loop on the end is used to remove the cancerous area and to burn away any remaining cancer cells with an electric current.
Radical cystectomy:
For invasive bladder cancer, the most common type of surgery is radical cystectomy, or when superficial cancer involves a large part of the bladder. Radical cystectomy is the removal of the entire bladder, the nearby lymph nodes, part of the urethra, and the nearby organs that may contain cancer cells. In men, the nearby organs that are removed are the prostate, seminal vesicles, and part of the vas deferens. In women, the uterus, ovaries, fallopian tubes, and part of the vagina are removed. If the entire bladder is removed, the patient may undergo another procedure to create a pouch to hold urine. Occassionally, small-localized, muscle-invasive bladder cancers can be removed sparing the remaining normal bladder, a procedure referred to as "partial" cystectomy. When bladder cancer has spread beyond the bladder, often the goal of surgery is not to remove the cancer itself, but to relieve the symptoms of the disease. Additional forms of therapy are then used to treat the cancer.
Radiation
therapy (also called radiotherapy) uses high-energy rays to kill cancer cells in one specific area. Radiation therapy can also be used to shrink a tumor before surgery, to make it easier to remove, or after surgery, to kill any cancer cells that may have been left behind.
External radiation:
This is usually done at least several days a week on an outpatient basis for several weeks. The high-energy rays are concentrated on the cancerous area from outside the body.
Internal radiation:
This is done by placing a small container of a radioactive substance into the bladder through the urethra or through an incision in the abdomen and requires a hospital stay. Once the implant is removed, no radioactivity is left in the body.
Chemotherapy
uses drugs to kill cancer cells. A single drug may be used, or a combination of drugs.

For patients with superficial bladder cancer, intravesical (inside the bladder) chemotherapy may be used after TUR. A catheter (tube) is placed through the urethra and into the bladder and used to fill the bladder with liquid forms of the drug(s) used. The drugs are left in the bladder for several hours and this treatment is usually done once a week for several weeks, then can be continued once or several times a month for up to a year.

For cancer that has spread through other parts of the body, chemotherapy drugs may be given intravenously, or through a vein that carries the drugs throughout the body. The drugs are usually given in cycles so that a recovery period follows every treatment period. Occassionally chemotherapy is also given before bladder surgery - cystectomy - as a means to facilitate surgery by reducing the tumor bulk. This is known as neoadjuvant therapy and has demonstrated survival benefit for many patients needing a radical cystectomy.

Immunotherapy, also known as biological therapy, uses the body's natural ability (immune system) to fight cancer and is most often used after TUR for superficial bladder cancer to prevent the cancer from coming back.

BCG is the most common form of immunotherapy. BCG solution contains live, weakened bacteria that stimulate the immune system to kill cancer cells in the bladder. The bladder is filled with the solution through a catheter and left for about two hours. This treatment is usually done once a week for about six weeks. Interferon is another form of biologic therapy that involves administration of large amounts of a synthetic protein normally made by the body to activate and energize the immune system. Recent studies suggest that a combination of BCG plus Interferon may be particularly active against aggressive or refractory superficial bladder cancer.

Michael O'Donnell, MD
Department of Urology
University of Iowa Hospitals and Clinics