CANCER

After bladder cancer has been diagnosed, tests are done to find out if cancer cells have spread within the bladder or to other parts of the body.

The process used to find out if cancer has spread within the bladder lining and muscle or to other parts of the body is called staging. The information gathered from the staging process determines the stageof the disease. It is important to know the stage in order to plan treatment. The following tests and procedures may be used in the staging process:

·         CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-raymachine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.

·         MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).

·         Chest x-ray : An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.

·         Bone scan : A procedure to check if there are rapidly dividing cells, such as cancer cells, in the bone. A very small amount of radioactive material is injected into a vein and travels through the bloodstream. The radioactive material collects in the bones and is detected by a scanner.

There are three ways that cancer spreads in the body.

The three ways that cancer spreads in the body are:

·         Through tissue. Cancer invades the surrounding normal tissue.

·         Through the lymph system. Cancer invades the lymph system and travels through the lymph vessels to other places in the body.

·         Through the blood. Cancer invades the veins and capillaries and travels through the blood to other places in the body.

When cancer cells break away from the primary (original) tumor and travel through the lymph or blood to other places in the body, another (secondary) tumor may form. This process is called metastasis. The secondary (metastatic) tumor is the same type of cancer as the primary tumor. For example, ifbreast cancer spreads to the bones, the cancer cells in the bones are actually breast cancer cells. The disease is metastatic breast cancer, not bone cancer.

The following stages are used for bladder cancer:

Stage 0 (Papillary Carcinoma and Carcinoma in Situ)

In stage 0, abnormal cells are found in tissue lining the inside of the bladder. These abnormal cells may become cancer and spread into nearby normal tissue. Stage 0 is divided into stage 0a and stage 0is, depending on the type of the tumor:

·         Stage 0a is also called papillary carcinoma, which may look like tiny mushrooms growing from the lining of the bladder.

·         Stage 0is is also called carcinoma in situ, which is a flat tumor on the tissue lining the inside of thebladder.

Stage I

In stage I, cancer has formed and spread to the layer of connective tissue next to the inner lining of thebladder.

Stage II

In stage II, cancer has spread to the layers of muscle tissue of the bladder.

Stage III

In stage III, cancer has spread from the bladder to the layer of fat surrounding it and may have spread to the reproductive organs (prostate, seminal vesicles, uterus, or vagina).

Stage IV

In stage IV, one or more of the following is true:

·         Cancer has spread from the bladder to the wall of the abdomen or pelvis.

·         Cancer has spread to one or more lymph nodes.

·         Cancer has spread to other parts of the body, such as the lung, bone, or liver.

·         Recurrent Bladder Cancer

·         Recurrent bladder cancer is cancer that has recurred (come back) after it has been treated. The cancer may come back in the bladder or in other parts of the body.

here are different types of treatment for patients with bladder cancer.

Different types of treatment are available for patients with bladder cancer. Some treatments arestandard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

Four types of standard treatment are used:

Surgery

One of the following types of surgery may be done:

·         Transurethral resection (TUR) with fulguration: Surgery in which a cystoscope (a thin lighted tube) is inserted into the bladder through the urethra. A tool with a small wire loop on the end is then used to remove the cancer or to burn the tumor away with high-energy electricity. This is known as fulguration.

·         Radical cystectomy: Surgery to remove the bladder and any lymph nodes and nearby organs that contain cancer. This surgery may be done when the bladder cancer invades the muscle wall, or when superficial cancer involves a large part of the bladder. In men, the nearby organs that are removed are the prostate and the seminal vesicles. In women, the uterus, the ovaries, and part of the vagina are removed. Sometimes, when the cancer has spread outside the bladder and cannot be completely removed, surgery to remove only the bladder may be done to reduce urinarysymptoms caused by the cancer. When the bladder must be removed, the surgeon creates another way for urine to leave the body.

·         Segmental cystectomy: Surgery to remove part of the bladder. This surgery may be done for patients who have a low-grade tumor that has invaded the wall of the bladder but is limited to one area of the bladder. Because only a part of the bladder is removed, patients are able to urinate normally after recovering from this surgery.

·         Urinary diversion: Surgery to make a new way for the body to store and pass urine.

Even if the doctor removes all the cancer that can be seen at the time of the surgery, some patients may be given chemotherapy after surgery to kill any cancer cells that are left. Treatment given after surgery, to lower the risk that the cancer will come back, is called adjuvant therapy.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stageof the cancer being treated.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into avein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). Bladder cancer may be treated with intravesical (into the bladder through a tube inserted into the urethra) chemotherapy. The way the chemotherapy is given depends on the type and stage of the cancer being treated.

See Drugs Approved for Bladder Cancer for more information.

Biologic therapy

Biologic therapy is a treatment that uses the patient’s immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body’s natural defenses against cancer. This type of cancer treatment is also called biotherapy or immunotherapy.

New types of treatment are being tested in clinical trials.

This summary section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied. Information about clinical trials is available from the NCI Web site.

Chemoprevention

Chemoprevention is the use of drugs, vitamins, or other substances to reduce the risk of developing cancer or to reduce the risk that cancer will recur (come back).

Photodynamic therapy

Photodynamic therapy (PDT) is a cancer treatment that uses a drug and a certain type of laser light to kill cancer cells. A drug that is not active until it is exposed to light is injected into a vein. The drug collects more in cancer cells than in normal cells. Fiberoptic tubes are then used to carry the laser light to the cancer cells, where the drug becomes active and kills the cells. Photodynamic therapy causes little damage to healthy tissue.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's listing of clinical trials.

Follow-up tests may be needed.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

A link to a list of current clinical trials is included for each treatment section. For some types or stagesof cancer, there may not be any trials listed. Check with your doctor for clinical trials that are not listed here but may be right for you.

Stage 0 (Papillary Carcinoma and Carcinoma in Situ)

Treatment of stage 0 may include the following:

·         Transurethral resection with fulguration.

·         Transurethral resection with fulguration followed by intravesical biologic therapy or chemotherapy.

·         Segmental cystectomy.

·         Radical cystectomy.

·         A clinical trial of photodynamic therapy.

·         A clinical trial of biologic therapy.

·         A clinical trial of chemoprevention therapy given after treatment so the condition will not recur(come back).

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients withstage 0 bladder cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.

Stage I Bladder Cancer

Treatment of stage I bladder cancer may include the following:

·         Transurethral resection with fulguration.

·         Transurethral resection with fulguration followed by intravesical biologic therapy or chemotherapy.

·         Segmental or radical cystectomy.

·         Radiation implants with or without external radiation therapy.

·         A clinical trial of chemoprevention therapy given after treatment to stop cancer from recurring(coming back).

·         A clinical trial of intravesical therapy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients withstage I bladder cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.

Stage II Bladder Cancer

Treatment of stage II bladder cancer may include the following:

·         Radical cystectomy with or without surgery to remove pelvic lymph nodes.

·         Combination chemotherapy followed by radical cystectomy.

·         External radiation therapy combined with chemotherapy.

·         Radiation implants before or after external radiation therapy.

·         Transurethral resection with fulguration.

·         Segmental cystectomy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients withstage II bladder cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.

Stage III Bladder Cancer

Treatment of stage III bladder cancer may include the following:

·         Radical cystectomy with or without surgery to remove pelvic lymph nodes.

·         Combination chemotherapy followed by radical cystectomy.

·         External radiation therapy combined with chemotherapy.

·         External radiation therapy with radiation implants.

·         Segmental cystectomy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients withstage III bladder cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.

Stage IV Bladder Cancer

Treatment of stage IV bladder cancer may include the following:

·         Radical cystectomy with surgery to remove pelvic lymph nodes.

·         External radiation therapy (may be as palliative therapy to relieve symptoms and improve quality of life).

·         Urinary diversion as palliative therapy to relieve symptoms and improve quality of life.

·         Cystectomy as palliative therapy to relieve symptoms and improve quality of life.

·         Chemotherapy alone or after local treatment (surgery or radiation therapy).

·         A clinical trial of chemotherapy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients withstage IV bladder cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.

Treatment Options for Recurrent Bladder Cancer

Treatment of recurrent bladder cancer depends on previous treatment and where the cancer hasrecurred. Treatment for recurrent bladder cancer may include the following:

·         Surgery.

·         Chemotherapy.

·         Radiation therapy.

·         A clinical trial of chemotherapy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients withrecurrent bladder cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.

Chemoradiation May Help Some Patients with Bladder Cancer Avoid Radical Surgery

Adapted from the NCI Cancer Bulletin.

Researchers in the United Kingdom have found that adding chemotherapyto radiation therapy as a treatment for bladder cancer may reduce the risk of a recurrence more than radiation alone, without causing a substantial increase in side effects.

The combined treatment approach—known as chemoradiation—was tested in 360 patients with muscle-invasive bladder cancer, a potentially deadly form of the disease. Results from the randomizedphase III study appeared April 19, 2012, in the New England Journal of Medicine.

“The success of this trial could mean that fewer patients need to have their bladders removed,” study co-leader Nick James, Ph.D., of the University of Birmingham, wrote in an e-mail message. “This approach also provides a viable treatment alternative for frailer patients who are too weak for surgery.”

The authors of an accompanying editorial agreed, calling the trial a “landmark” study.

“These data are really quite compelling,” said one of the editorialists, William Shipley, M.D., of Massachusetts General Hospital and Harvard Medical School. Chemoradiation, he continued, can now be regarded as one of several treatment options for patients with muscle-invasive bladder cancer and their physicians to consider.

Preserving the Bladder

In the study, 182 participants were randomly assigned to receive chemotherapy with fluorouracil andmitomycin C in addition to radiation therapy; the other 178 received radiation therapy alone. All participants had muscle-invasive bladder cancer.

Thirty-three percent of the patients who received chemoradiation experienced a relapse in the bladder or in the surrounding tissues within 2 years, compared with 46 percent of those who had radiation therapy alone. The results also showed that, after a median follow-up of about 70 months, the addition of chemotherapy cut the relative risk of invasive disease recurrence by almost half.

There was not a statistically significant difference in overall survival between the chemoradiation and radiation-only groups. More patients in the radiation-only group than in the chemoradiation group had their bladders surgically removed (cystectomy) following a recurrence, and the researchers noted that this increased rate of surgery could make it difficult to determine whether the combination treatment improves survival.

Although the trial did not directly compare chemoradiation with surgical removal of the bladder, the findings add to evidence that a considerable proportion of patients with muscle-invasive bladder cancer can avoid radical surgery for the disease, noted Bhadrasain Vikram, M.D., chief of the Clinical Radiation Oncology Branch of NCI’s Radiation Research Program.

“These trials are hard to do because of the relative rarity of muscle-invasive bladder cancer and—especially in the United States—the conviction of many urologists that removal of the bladder is the preferred treatment whenever possible,” Dr. Vikram added. (Non-muscle-invasive bladder cancers are not life threatening, and minor surgery during cystoscopy is often effective.)

Similar Results Seen in Anal Cancer

The rationale behind testing chemoradiation for bladder cancer was that the chemotherapy would make the radiation therapy more effective, as has been demonstrated in some other cancers. Indeed, the new results mirror the experience of patients with anal cancer, who have been able to avoid the trauma of having the anus removed surgically, noted Dr. Shipley.

When chemotherapy is used to treat bladder cancer in the United States, doctors have traditionally used cisplatin-based combinations rather than fluorouracil and mitomycin C. It will be up to individual physicians to decide which drug to use in a chemoradiation regimen, the editorialists noted.

Regardless of which drugs are used, surgery will remain a critical option for patients treated with an organ-preservation strategy. Patients who have a recurrence after receiving chemoradiation need additional treatment such as surgery; not all patients are candidates for surgery, however.

“Although chemoradiation presents an option for patients who are ineligible for surgery, the current study does not specifically address this patient population,” said Matthew Milowsky, M.D., co-director of the urologic oncology program at UNC Lineberger Comprehensive Cancer Center in Chapel Hill, NC. “This approach is not for all patients, and it is important to appropriately select patients for bladder preservation therapy,” he added.

Matching Patients to Therapies

Future studies will assess potential tumor markers that could help identify candidates for the procedure at the time of diagnosis. One potential marker is a protein called MRE11, which is involved in the cellular response to radiation-induced DNA damage, Dr. Shipley noted.

In the meantime, the new results could increase interest in strategies that aim to preserve the bladder. “Removing the bladder is a major operation with implications for the rest of the patient’s life,” said study co-leader Robert Huddart, Ph.D., from the Institute of Cancer Research and the Royal Marsden NHS Foundation Trust, in a statement.

In the United States, bladder preservation is underutilized, noted Howard Sandler, M.D., chair of Radiation Oncology at Cedars-Sinai Medical Center. The vast majority of patients who are eligible for surgery get surgery, he said, in part because there are few good studies comparing radiation-based approaches with surgery.

“The take-home message of this study is that patients with muscle-invasive bladder cancer should have a discussion with their physicians about the role of bladder preservation using chemotherapy and radiation therapy,” said Dr. Sandler.