Understanding Genetic Changes in Bladder Cancer

During the past decade scientists have made great progress in learning about the differences between normal cells and cancer cells. They are also finding out how these differences cause cells to grow too much and spread to other parts of the body. Several changes in the DNA (genetic material) of bladder cancers have been found. These findings have advanced our understanding of this disease. The purpose of these studies is to decide if tests to identify these DNA abnormalities are useful in finding bladder cancers that recur (come back) after treatment. Other studies are in progress to decide if tests to find these DNA abnormalities can help predict the prognosis (outlook) of bladder cancer patients and if this information is useful in choosing treatment.

Chemoprevention

Patients who have had one bladder cancer that has been successfully treated are at risk for developing a new cancer in the lining of their kidneys, ureters, urethra, or at another location in their bladder. Researchers are currently studying some vitamins, such as vitamin C and vitamin A-like drugs, and drugs such as nonsteroidal anti-inflammatory drugs such as celecoxib (Celebrex) that may be useful in preventing these new cancers from developing.

Urine Tests to Find Bladder Cancer Recurrence After Treatment

The Food and Drug Administration (FDA) has recently approved 2 new urine tumor marker tests for finding recurrent bladder cancer after treatment. One test, BTA, looks for proteins in the urine that indicate the presence of recurrent cancer cells. The other test, NMP22, measures the level of a protein from the nucleus of the bladder cancer cells. Other new markers are being tested. These are called HA-HAase, CYFRA 21-1. Also an antibody to whole cells called Immunocyt is being tested.

The usual test for finding bladder cancer that has recurred locally is urine cytology (viewing cells from urine under the microscope). Urine cytology is very effective in finding high-grade bladder cancers, but will miss the majority of papillary urothelial neoplasms of low malignant potential, and some low-grade papillary bladder cancers.

Although these low-grade cancers are usually superficial and rarely life-threatening, a more sensitive test for low-grade cancers would be an important advance. The BTA and NMP22 tests are more sensitive than cytology in picking up low-grade bladder cancers (more sensitive means the tests miss fewer cancers).

Both tests are less specific, meaning that patients with no cancer may have false-positive results. False positives seem to be less of a problem with the NMP22 test. Both tests are currently being tested and some doctors may recommend one or both tests for some patients. None of these markers has replaced cystoscopy although they may be useful in reducing the number of these procedures.

Another experimental test measures an enzyme called telomerase that is released by most cancer cells, but only rarely by normal cells. Preliminary studies suggest this test may be useful in finding recurrent bladder cancer.

The FDA has recently approved a test that uses a process called fluorescence in situ hybridization assay (FISH) to screen patients for recurrent bladder cancer. This test, which measures abnormalities in several chromosomes frequently found in transitional cell bladder cancers, was more accurate than urine cytology and at least equivalent to the BTA test in a recently reported study. The FISH assay causes abnormal cells to glow (fluoresce) if they contain the abnormal changes in the chromosome.

In some patients, FISH found evidence of recurrent cancer before the tumor could be seen on cystoscopy.

Photodynamic Therapy

Photodynamic therapy (PDT) is a new method that may be useful in treating early stages of bladder cancer. It is not yet widely available. PDT begins with the injection of a nontoxic chemical into the blood. This chemical is allowed to collect in the tumor for a few days. A special type of laser light is then focused on the cancer. This light causes changes in the chemical that has collected inside the cancer cells. The light changes the nontoxic chemical into a new chemical that can kill cancer cells.

The advantage of PDT is that it can kill cancer cells with very little harm to normal cells. One drawback is that the chemical must be activated by light, so only cancers near the surface of the bladder, which can be reached by shining a special light through the cystoscope, can be treated in this way. This light cannot reach cancers that have spread deeper into the bladder wall or to other organs.

Side effects of PDT include redness or discoloration of the skin and sensitivity to the sun or to other light sources. These can last for up to 6 weeks after therapy and in some cases may be severe.

Chemotherapy

Valrubicin was approved in 1998 by the Food and Drug Administration (FDA) for intravesical chemotherapy in patients with bladder carcinoma in situ (stage 0is), who did not respond to BCG treatment and who are not surgical candidates for cystectomy. A recent study found that heating the inside of the bladder with microwaves, may increase the effectiveness of intravesical chemotherapy.

Other chemotherapy drugs such as paclitaxel, carboplatin, vinflunine, and gemcitabine are being tested as treatment for advanced bladder cancer.

Anti-angiogenesis Drugs

Antiangiogenesis drugs (which kill cancers by stopping their blood supply) such as Bevacizumab (Avastin) and sorafenib (Nexavar) have been effective against colorectal cancer and kidney cancer, and are currently being tested in patients with bladder cancer.

Targeted Therapies

Researchers are learning more about the molecules within bladder cancer cells that control their growth and spread in order to develop new targeted therapies. Some of these drugs have been found to be useful in other cancers, such as lung cancer and colorectal cancer. Several clinical trials are in progress to test targeted drugs such as lapatinib, Erlotinib (Tarceva), Trastuzumab (Herceptin) and gefitinib (Iressa) against bladder cancer.

Gene Therapy: Gene therapy is another new method being tested for bladder cancer. One of these approaches uses special viruses that have been modified in the laboratory. The modified virus is injected into the bladder and infects the bladder cancer cells. When this infection occurs, the virus injects a gene into the cells for GM-CSF, an immune system hormone (cytokine) that may help activate immune system cells to attack the cancer. Last Revised: 08/08/2006