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Bladder cancer

Definition

Bladder cancer is the second most common urologic cancer in adults. There are 67,000 new cases of bladder cancer each year in the United States.

Urothelial carcinoma, formally known as transitional cell carcinoma, is the most common type of bladder cancer. Urothelial carcinoma of the bladder may present in several different forms, including:

  • Carcinoma in situ, or CIS
  • Papillary carcinoma
  • Sessile carcinoma

The grade, depth of invasion and involvement of the bladder muscle determine the risk, prognosis and treatment. Bladder cancer can be classified into two broad categories — non-muscle-invasive and muscle-invasive-urothelial-carcinoma.

Alternate names

Bladder Carcinoma; Urothelial Carcinoma of the Bladder

Causes, incidence and risk factors

Bladder cancer tends to occur most commonly in individuals over the age of 60 and is about two to three times more common in men than in women. Cigarette smoking and exposure to certain industrial chemicals (derivatives of compounds called arylamines and petrochemicals) are strongly associated with the development of bladder cancer.

Types

Non-muscle-invasive Bladder Cancer

At the initial diagnosis, approximately 70 percent of patients with urothelial carcinoma have non-muscle-invasive cancers, but 50 percent to 70 percent of these patients have a recurrence within five years of treatment. Ten to 20 percent of superficial lesions progress to deep muscle invasive disease. Papillary tumors respond well to conservative treatment and are easily removed endoscopically (through a camera placed via the urethra without a surgical incision). The rate of recurrence is approximately 70 percent; therefore additional treatment to prevent recurrence is usually prescribed in the form of intravesical therapy (medicine placed directly into the bladder through a catheter) and follow-up examinations are important. Although limited to the surface lining of the bladder, CIS tends to cause symptoms more frequently and may signal biologically aggressive disease. The risk of progression is 4 percent to 8 percent, with some patients having a more rapid progression than papillary tumors. The overall five-year survival for patients with non-muscle-invasive and localized bladder cancer is greater than 92 percent with appropriate treatment.

Muscle-Invasive and Advanced Bladder Cancer

Between 20 percent and 25 percent of new cases of bladder cancer are muscle-invasive. Muscle-invasive bladder cancer is more aggressive than noninvasive disease, and approximately 50 percent of patients with muscle invasive disease will experience cancer recurrence, with disease spreading throughout the body after therapy. Survival depends on disease stage and treatment; for organ-confined disease treated with surgery and in cases responsive to chemotherapy before cystectomy, five-year survival is 85 percent. Common sites of disease spread beyond the bladder include regional lymph nodes, bone, liver and lung. Survival decreases with more advanced disease. Five-year survival is approximately 50 percent in regionally advanced (lymph node positive) bladder cancer and <10 percent in the presence of distant metastases.

Signs and symptoms

Hematuria

  • Gross (Blood that you can see in the urine)
  • Microscopic (Blood that can only be seen with a microscope)

Irritative Urination Symptoms

  • Pain
  • Burning
  • Frequency
  • Incomplete emptying

For the majority of people, the first symptom of bladder cancer is blood in the urine, called hematuria. Hematuria is either gross (viewable with the naked eye) or microscopic.

Irritative urination symptoms may also be associated with bladder cancer and include pain and burning on urination, frequency and incomplete emptying of the bladder. It is important not to assume that blood in the urine is only from a bladder infection. Patients should be evaluated for bladder cancer who are treated for a bladder infection and hematuria continues.

Tests, treatments

Tests

After taking a detailed medical history, the urologist will examine a urine specimen and check for evidence of blood and signs of infection.

The standard for the evaluation of the bladder for cancer is direct visual examination with a specialized instrument call a cystoscope. A cystoscope is a small camera inserted into the bladder. The purpose of routine office cystoscopy is to evaluate the lining of the bladder and the urethra, the channel where urine passes out of the bladder and then exits the body. If abnormalities such as tumors or patches of abnormal-appearing tissue are discovered during cystoscopy, a biopsy or a sample of tissue may be taken at that time to determine the presence of cancer. However, your urologist will most likely recommend the biopsy to take place in the operating room.

Because urothelial carcinoma can also occur in the lining of the ureters and kidneys, routine surveillance of these organs is also important after a diagnosis of bladder cancer. Several tests can be used to evaluate the upper tracks, including a CT scan or MRI. These tests will also evaluate the structures around the bladder, including the pelvic lymph nodes.

Urine specimens will also be examined for abnormal cells. High-grade cancers readily shed tumors cells into the voided urine allowing for pathologic examination of the urine specimen (cytology) for the presence of tumor cells. Additional urine tests are available and may be ordered by your doctor if the urine cytology tests are inconclusive.

Clinical staging is also performed with transurethral resection, or TUR; CT scan; and exam under anesthesia, or EUA. EUA allows the surgeon to manually assess the bladder after TUR for the presence of tumor.

Prognosis and treatment for bladder cancer is directly linked to the stage of the bladder cancer. Staging is a process that demonstrates how far the cancer has spread. The treatment and prognosis or outlook for bladder cancer will depend significantly on its stage.

TNM System stands for Tumor, Lymph Nodes and Metastasis. Combining the individual components of the TNM system will provide the stage of disease. Stages for bladder cancer range from 1 through 4, with stage 1 having the best prognosis and stage 4 having the worst prognosis.

Treatment

The majority of bladder cancers arise from the lining of the bladder (non-invasive tumors). Treatment for non-muscle-invasive bladder cancer can include:

• Cystoscopy with cautery destruction of the tumor
• Intravesical drug therapy
• TUR (transurethral resection)

Most modern cystoscopes are equipped with channels that permit small instruments to be passed into the bladder for the purpose of removing tissue, stopping bleeding with a special electrical device called an electro cautery or even performing laser treatment. If the bladder cancer is small enough, this cautery may be used to remove the cancer.

Intravesical therapy is the use of one of several different types of medical therapies placed directly into the bladder through a urethral catheter. Therapies consist of drugs placed in the bladder in an attempt to minimize the risk of tumor recurrence and progression. These drugs come from a wide variety of sources. About 50 percent to 68 percent of patients with superficial bladder cancer have a very good response to intra-vesical therapy. The most commonly used intravesical therapy is Bacille Calmette-Guerin, or BCG, which is administered once a week for six straight weeks. BCG is a weakened tuberculosis bacterium. Maintenance therapy (repeated therapy on a regular basis) with BCG or another drug administered intermittently after initial diagnosis and treatment of superficial bladder tumor decreases the likelihood of recurrence.

A transurethral resection is a procedure performed through the cystoscope whereby the tumor is resected without making a visible incision on the body. This procedure is a crucial part of the diagnosis and staging of bladder cancer. A small camera is inserted into the bladder to visualize the bladder. The entire removal of a bladder tumor can be accomplished through this operative cystoscope for diagnosis and treatment. Sometimes a bladder tumor will be too large for transurethral resection.
Drug therapy after TUR is commonly prescribed for patients and is based upon risk of recurrence. Risk of recurrence is based upon tumor size, stage and grade, and the number of tumors. Additionally, a single dose of chemotherapy may be recommended immediately after TUR to decrease the risk of cancer recurrence.

The biopsy specimen or TUR specimen is sent to the pathologist, who evaluates the specimen for the presence, extent (stage) and aggressiveness (grade) of cancerous cells. Surveillance is required after diagnosis for bladder cancer. Patients are monitored with office cystoscopy and urine cytology in the office for stage 1 tumors. The frequency of monitoring is based upon the stage and grade of the cancer.

Invasive bladder cancer is cancer that has invaded into the bladder wall or outside the bladder. Invasive bladder cancer treatment options are drastically different than those for superficial bladder cancer.

Invasive Bladder Cancer Treatment Options:

  • In patients with stage 2 or stage 3 bladder cancer, cystectomy is often the treatment of choice in patients who are good surgical candidates. In men who undergo a cystectomy with urinary diversion, the bladder and prostate are removed. In women, the bladder, uterus, fallopian tubes, ovaries and anterior portion of the vagina are removed. Surrounding lymph nodes in the pelvis are removed to assess the extent or spread of the cancer. Next, one of several reconstruction options, known as a urinary diversion, is available to eliminate urine from the body.
  • Chemotherapy is a systemic treatment (i.e., drug that is dispersed throughout the entire body) designed to kill cancer cells. Typically, it is administered intravenously (through a vein). The chemotherapy may be administered before surgery (neoadjuvant therapy), after surgery (adjuvant therapy) or in the setting of advanced (stage 4) disease. On the other hand, in patients with noninvasive bladder cancer, chemotherapy may be infused into the bladder through the urethra (called intravesical chemotherapy) in hopes of reducing recurrence and progression of disease.
  • Radiation therapy with chemotherapy is another treatment option. Radiation uses high-energy X-rays to destroy cancer cells. The addition of systemic chemotherapy renders cancer cells more susceptible to the killing effects of radiation. Radiation therapy can be used to treat stage 2 and stage 3 bladder cancer in select patients. The benefit of this approach is keeping the bladder in place and potentially avoiding bladder removal surgery. Radiation therapy is also used to relieve symptoms (called palliative treatment) of advanced bladder cancer.

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