Bladder Cancer

Definition

Bladder cancer is a malignant tumor within the bladder. In the United States, bladder cancers usually start from the cells lining the bladder (transitional cells). These tumors may be classified based on their growth pattern:

  • Papillary tumors have a wart-like appearance and are attached to a stalk.
  • Nonpapillary tumors are much less common, but they are more invasive and have a poorer prognosis.

Causes, incidence, and risk factors

As with most other cancers, the exact cause is uncertain. However, several factors may contribute to the development of bladder cancer. Cigarette smoking increases the risk of developing bladder cancer by a factor of nearly five, compared to non-smokers. As many as 50% of all bladder cancers in men and 30% in women may be attributable to cigarette smoke. This risk does show a gradual decline in people who quit smoking.

About one in four cases of bladder cancer can be attributed to workplace exposure to carcinogens (cancer-causing chemicals). Arylamines are the chemicals most responsible. Dye workers, rubber workers, aluminum workers, leather workers, truck drivers, and pesticide applicators are at the highest risk, although arylamines have been reduced or eliminated in many workplaces.

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).

A 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 increase the risk of 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. There are several different ways to stage tumors. Recently, the TNM staging system has become common. This staging system contains several substages, but it basically categorizes tumors using the following scale:

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

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

Symptoms

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 critical.

  • 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)

Signs and tests

A 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)

Treatment

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, stage 0 and I tumors are treated by removing the tumor without removing the rest of the bladder. They sometimes may also be treated by administering chemotherapy or immunotherapy (see below) directly into the bladder. Because the risk of the cancer returning is so high, people with bladder cancer require constant follow-up for the rest of their lives.

The treatment for patients with stage II and stage III disease is changing. While the accepted treatment has been removing the entire bladder (in a surgery called radical cystectomy), there is growing interest in keeping as much of the bladder as possible. Some patients may be treated by removing only part of the bladder, and that procedure is followed by radiation and chemotherapy. Some patients may be treated with chemotherapy before surgery, to try and shrink their tumor down, so that they might be able to avoid having the entire bladder removed. However, many people with stage II and stage III tumors still require bladder removal. In some patients with stage III tumors who choose not to have surgery, or who cannot tolerate surgery, a combination of chemotherapy and radiation may be used.

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

CHEMOTHERAPY

Chemotherapy for bladder cancer can be administered through a vein or into the bladder. For early disease (stages 0 and I), it is usually given directly into the bladder. For more advanced stages (II-IV), treatment is usually given by vein.

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

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

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

The combination of two of these drugs, gemcitabine and cisplatin, has been shown to be as effective with less side effects as an older regimen known as MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin). Many centers have replaced MVAC with this new combination. Paclitaxel and carboplatin is another effective combination that is frequently used.

A Foley catheter can be used to instill the medication directly into the bladder of patients with stage I disease. The catheter is removed immediately after the medication has been instilled. 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 completely expose the entire bladder wall to the medication.

Several different types of chemotherapy medications may be delivered directly into the bladder. They include:

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

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

IMMUNOTHERAPY

Bladder cancers are often treated by immunotherapy, in which a medication causes your own immune system to attack and kill the tumor cells. Immunotherapy for bladder cancer is usually performed using Bacille Calmette-Guerin (commonly known as BCG), which is a solution of genetically changed tuberculosis bacteria. Because they were genetically modified, these bacteria are not able to produce infection. BCG is administered through a Foley catheter directly into the bladder. Since BCG is a biological agent, special precautions must be taken during its handling and administration.

Potential side effects include bladder irritability, urinary frequency, urinary urgency, and painful urination. These are reported by 90% of the people treated with BCG. However, the symptoms usually resolve within a few days after treatment. Rare side effects include blood in the urine, malaise, nausea, chills, joint pain, and itching. Rarely, a systemic tuberculosis (TB) infection can develop, requiring treatment with anti-tuberculosis medication. Systemic infection is suspected if you develop an elevated temperature that lasts for more than one day.

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 surgical procedure is performed under general or spinal anesthesia. A cutting instrument is then inserted through the urethra to remove the bladder tumor.

BLADDER REMOVAL

Many people with stage II or III bladder cancer may require bladder removal (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. For those patients who undergo complete bladder removal, chemotherapy is also given after surgery to decrease the risk of a recurrence.

Radical cystectomy in men usually involves removal of 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 for examination in the laboratory. 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 (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, 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.

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 or "new bladder"), then attached to the urethral stump, which is the beginning of where the urine normally empties from the bladder.

This procedure allows patients to maintain some degree of normal urinary control, although there are complications, and the urination is usually not the same as before surgery. For example, this procedure can be associated with leakage of urine at night, the need to perform manual catheterization periodically, and other complications listed above for the continent urinary reservoir.

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

Expectations (prognosis)

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

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

How well a patient does depends on the specific stage of bladder cancer and the type of treatment chosen. The prognosis for stage 0 or I cancers is fairly good, although the risk of the cancer returning is high. However, most bladder cancers that return can be surgically removed and cured.

The cure rates for patients with stage III tumors are less than 50%. Patients with stage IV are rarely cured (although patients with only a few metastatic lesions can be cured in some circumstances).

Complications

Bladder cancers may spread into the nearby organs or may travel through the pelvic lymph nodes, and metastasize to the liver, lungs, and bones. Additional complications of bladder cancer include anemia, hydronephrosis (swelling of the ureters causing kidney injury), urinary incontinence, and urethral stricture.