The bladder is a hollow organ in the lower abdomen. Its primary function is to store urine, the waste that is produced when the kidneys filter the blood. Urine passes from the two kidneys into the bladder through two tubes called ureters and urine leaves the bladder through another tube called the urethra. The bladder has a muscular wall that allows it to get larger and smaller as urine is stored or emptied.

The wall of the bladder is lined with several layers of cells called transitional cells. Cancer arising from these cells makes up more than 90% of all bladder cancers and these are referred to as transitional cell carcinomas. Because transitional cell carcinomas are the most common type of bladder cancer, the information in this section only addresses treatment of transitional cell cancer of the bladder.

Bladder cancer occurs predominantly in elderly men and less frequently in women and younger men. Many bladder cancers are thought to be caused by exposure to cancer-causing agents that pass through the urine and come into contact with the bladder lining. The most important risk factor for bladder cancer is smoking, which increases risk by at least four-fold.

The most common sign of bladder cancer is hematuria or blood in the urine, which will turn the urine rust or red in color. Other signs of bladder cancer may include pain during urination and frequent urination. Most patients with bladder cancer do not have symptoms other than hematuria. Unfortunately, most bladder cancers are not diagnosed until they have become very large. As a result, research is ongoing in order to develop urine tests that would enable earlier detection of bladder cancer when it is small and more easily treated. There are several promising tests under evaluation, but currently none are reliable enough for routine use.

An outpatient procedure called a cystoscopy is usually used to diagnose bladder cancer. During a cystoscopy, the physician (a urologist) inserts a thin, lighted tube (cystoscope) into the bladder through the urethra to examine the internal lining of the bladder. The procedure enables the urologist to remove (biopsy) small samples of any abnormal appearing areas of the bladder and examine them under the microscope. When bladder cancer is diagnosed, the urologist will want to learn the stage or extent of the cancer, as well as the grade (aggressiveness) of the cancer as determined by its appearance under the microscope. Grade is important because it indicates how closely the cancer resembles normal tissue and suggests how fast the cancer is likely to grow. Low-grade cancers more closely resemble normal tissue and are likely to grow and spread more slowly than high-grade cancers.

Staging is an attempt to determine the extent to which the cancer has spread. The stage of bladder cancer may be determined at the time of diagnosis or it may be necessary to perform additional tests such as computerized tomography (CT) scans, magnetic resonance imaging (MRI) or an intravenous pyelogram (IVP), a procedure which involves the injection of dye into the blood. When the dye (contrast) travels through the kidneys and ureters, it allows them to be visualized with X-rays (fluoroscopy).

Some risk factors, such as a genetic mutation within a gene called the p53 gene, are associated with a poor outcome following treatment with chemotherapy and/or radiation therapy. Therefore, physicians may look for the presence of such risk factors upon a diagnosis of bladder cancer in order to best plan a treatment regimen. Research is ongoing to identify risk factors that are associated with a poor outcome, as well as factors that indicate that some patients may require less treatment. By identifying such factors, physicians are better able to tailor treatment to meet the needs of individual patients.

Cancers confined to the inner lining of the bladder are called "superficial" and comprise 70-80% of all bladder cancers. Cancers that have spread into the bladder wall are called "deep" bladder cancers and those that have spread to lymph nodes and/or distantly to lungs, liver or other organs are referred to as "metastatic.” In order to learn more about the most recent information available concerning the treatment of bladder cancer, click on the appropriate stage.

Stage 0 (T0) : Patients with stage 0 bladder cancer have the earliest stage of cancer that involves only the innermost layers of cells in the bladder. Depending upon the appearance of the cells under the microscope, stage 0 transitional bladder cancer is pathologically classified as either noninvasive papillary carcinoma or carcinoma in situ (CIS), both of which are considered to be "superficial” bladder cancers.

Stage I (T1): Patients with stage I bladder cancer have cancer that invades beneath the surface of the bladder into connective tissue, but does not invade the muscle of the bladder and has not spread to lymph nodes. This is also classified as a "superficial bladder cancer.”

Stage II (T2): Patients with stage II bladder cancer have cancer that invades through the connective tissue into the muscle wall, but has not spread outside the bladder wall or to local lymph nodes. Patients with cancer invading the inner half of the muscle of the bladder wall have a better outcome than patients with invasion into the deep muscle (outer half of the muscle of the bladder wall). Stage II bladder cancer is classified as a "deep" or "invasive" bladder cancer.

Stage III (T3): Patients with stage III bladder cancer have cancer that invades through the connective tissue and muscle and into the immediate tissue outside the bladder and/or invades the prostate gland in males or the uterus and/or vagina in females. With stage III bladder cancer, there is no spread to lymph nodes or distant sites. Stage III bladder cancer is also classified as a "deep" or "invasive" bladder cancer.

Stage IV (T4): Patients with stage IV bladder cancer have cancer that has extended through the bladder wall and invaded the pelvic and/or abdominal wall and/or has lymph node involvement and/or spread to distant sites. Stage IV bladder cancer is also referred to as "metastatic" bladder cancer. Recurrent Bladder Cancer: Patients with recurrent bladder cancer have cancer that has returned following initial treatment with surgery, radiation, chemotherapy or immunotherapy.

Recurrent: Patients with recurrent bladder cancer have cancer that has returned following initial treatment with surgery, radiation, chemotherapy or immunotherapy.

Surgery

Radiation Therapy

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Patients with Stage 0 (Ta or Tis)  bladder cancer have the earliest stage of bladder cancer that involves only the surface layer of the bladder. Depending upon the appearance of cancer cells under the microscope, Stage 0 bladder cancer is pathologically classified as a non-invasive papillary carcinoma or carcinoma in situ (CIS).

A variety of factors ultimately influence a patient's decision to receive treatment of cancer. The purpose of receiving cancer treatment may be to improve symptoms through local control of the cancer, increase a patient's chance of cure, or prolong a patient's survival. The potential benefits of receiving cancer treatment must be carefully balanced with the potential risks of receiving cancer treatment.

The following is a general overview of the treatment of Stage 0 bladder cancer. Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied to your situation. The information on this Web site is intended to help educate you about your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.

Most new treatments are developed in clinical trials. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Participation in a clinical trial may offer access to better treatments and advance the existing knowledge about treatment of this cancer. Clinical trials are available for most stages of cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. To ensure that you are receiving the optimal treatment of your cancer, it is important to stay informed and follow the cancer news in order to learn about new treatments and the results of clinical trials.

Both non-invasive papillary carcinoma and carcinoma in situ are classified as superficial bladder cancers. Standard treatment of superficial bladder cancer is surgical removal and adjuvant therapy to decrease the risk of recurrent cancer or progression to more invasive disease. Despite standard treatment, the majority of patients with superficial bladder cancer experience recurrence of their cancer. Research is ongoing to evaluate several new approaches for the treatment of superficial or recurrent superficial bladder cancer.

Papillary carcinoma of the bladder is a superficial cancer that grows on the surface of the bladder and can be easily removed with surgery. Standard treatment of papillary carcinoma is a transurethral resection (TUR). A TUR is an operation that is performed for both the diagnosis and management of bladder cancer. During a TUR, a urologist inserts a thin, lighted tube called a cystoscope into the bladder through the urethra to examine the lining of the bladder. The urologist can remove samples of tissue through this tube or can remove some or all of the cancer in the bladder.

Following a TUR, the standard approach for the management of patients with non-invasive papillary carcinoma is surveillance, which means frequent follow-up examinations. During surveillance, patients undergo frequent evaluations performed at regular intervals to detect recurrent or new cancers before they become invasive. Routine surveillance tests include urinary cytology (looking for new cancer cells in the urine) and direct visualization of the lining of the bladder (cystoscopy) typically performed every 3 months. Recurrences can be expected to occur in 50-75% of patients but are usually of the same grade and stage as the original cancer and can be successfully treated by repeat TUR. To learn more about TUR, go to Surgery for Bladder Cancer.

Carcinoma in situ is a superficial bladder cancer that is confined to the surface layer of the bladder. The cellular growth pattern of CIS differs from that of papillary carcinoma. Furthermore, CIS is more likely than papillary carcinoma to lead to invasive bladder cancer.

All patients with CIS are initially treated with transurethral resection (TUR), biopsy with electrical (cautery) or laser thermal destruction of all visualized cancer. Radical cystectomy (complete removal of the bladder) is used for treatment of extensive multiple superficial cancers or CIS unresponsive to intravesical therapies. To learn more, go to Surgery for Bladder Cancer.

TUR alone is effective in preventing recurrences in approximately 50% of patients with superficial bladder cancer. Failure of treatment is usually due to the appearance of new superficial cancers, which can be retreated with TUR and cautery or laser therapies. Within 15 or 20 years, more than half of surviving patients will have experienced progressive cancer or have developed new cancers, including cancers of the upper urinary tract (ureters and pelvis of the kidney). Approximately 20-30% of these cancers will require treatment with cystectomy.

Since this is a cancer of older individuals, many patients will die of other causes before progression of bladder cancer. However, approximately 25% of patients treated for superficial bladder cancer will ultimately die of bladder cancer. Since the risk of developing invasive bladder cancer never goes away, it is important to have frequent follow-up examinations (cystoscopy) no matter what form of therapy is selected. It is extremely important to detect early progression because there are effective treatments for small invasive bladder cancers.

Since recurrences of bladder cancer can occur frequently, it is important to develop strategies to prevent these recurrences. Adjuvant therapy is additional treatment that increases the effectiveness of a primary therapy. The goal of adjuvant therapy is to improve the chance of cure, prevent cancer from recurring or progressing to a worse stage, and/or improve the duration of overall survival. Adjuvant therapy for papillary carcinoma and carcinoma in situ typically consists of chemotherapy and/or immunotherapy delivered directly into the bladder through the urethra (intravesical therapy). Patients with carcinoma in situ are at particular risk not only for superficial cancer recurrences, but also for progression to more aggressive invasive bladder cancers. All patients with this stage of disease should consider adjuvant treatment.

Bladder Instillation of Bacille Calmette-Guérin (BCG): Bacille Calmette-Guérin (BCG) is one of the most common adjuvant therapies for treatment of superficial bladder cancer, and is commonly used for patients with high-grade papillary cancers or carcinoma in situ. BCG is an immunotherapy that is a weakened form of the bacterium related to bacteria causing tuberculosis. BCG is instilled directly into the bladder through the urethra and exerts its anti-cancer effect by stimulating the body’s immune system to kill cancer cells. The primary side effects of BCG are pain in the bladder, blood in the urine and rarely, autoimmune disorders. Because BCG is a live bacteria, it may occasionally grow and cause an infection that requires antibiotic treatment.

Compared to treatment of superficial bladder cancer with TUR alone, treatment with TUR and intravesical BCG reduces the risk of recurrence and may also reduce the risk of cancer progression. However, even with optimal BCG therapy, many patients with superficial bladder cancer will ultimately have progression to invasive bladder cancer. This indicates the importance of frequent follow-up examinations (cystoscopy) to detect early progression to invasive cancer or new superficial cancers. Early invasive bladder cancer can be treated effectively.

Bladder Instillation of Chemotherapy: Instillation of chemotherapy drugs (mitomycin, thiotepa, or doxorubicin) into the bladder can reduce the incidence of superficial cancer recurrences, but no single drug has been confirmed to reduce progression of superficial cancer to invasive bladder cancer. This means that multiple small new cancers can be prevented, but progression to a more invasive bladder cancer may occur despite treatment.

The optimal time to administer chemotherapy is immediately after TUR, as the drugs might prevent reseeding of cancer cells that were disrupted with surgery. Mitomycin is probably the preferred drug because it produces few side effects and is not well absorbed into the system, which allows more of the drug to remain in the bladder to treat the cancer. Thiotepa is rapidly absorbed and produces low blood counts. Doxorubicin produces the most local side effects.

Strategies to Improve Treatment

The progress that has been made in the treatment of bladder cancer has resulted from improved surgical techniques, development of adjuvant treatments and doctor and patient participation in clinical studies. Future progress in the treatment of bladder cancer will result from continued participation in appropriate studies. Currently, there are several areas of active exploration to improve the treatment of bladder cancer.

Supportive Care: Supportive care refers to treatments designed to prevent and control the side effects of cancer and its treatment. Side effects not only cause patients discomfort, but also may prevent the optimal delivery of therapy at its planned dose and schedule. In order to achieve optimal outcomes from treatment and improve quality of life, it is imperative that side effects resulting from cancer and its treatment are appropriately managed. For more information, go to Managing Side Effects.

Photodynamic Therapy: Photodynamic therapy combines a photosensitizer, such as Photofrin®, with red laser light to destroy cancer cells. The photosensitizer is injected into a vein, travels through the bloodstream and is picked up and incorporated into cancer cells. When the laser is directed at the cancer, the photosensitizer in the cancer cell captures the light from the laser, which kills the cell.

Photodynamic therapy was evaluated in 58 patients with resistant superficial bladder cancer (papillary and carcinoma in situ) who could not receive local treatment with chemotherapy or BCG immunotherapy. With a single photodynamic treatment, 84% of patients with residual resistant papillary transitional cell carcinoma and 75% of patients with refractory carcinoma in situ experienced a complete response or disappearance of all cancer. At 4 years from treatment, 59% of the patients responding to treatment were alive and 31 of 34 survived without cancer recurrence. Photodynamic therapy appears to be a safe and effective treatment for refractory carcinoma in situ or recurrent papillary transitional cell carcinoma. Clinical trials are ongoing to determine how best to utilize this form of treatment.

Combining Other Agents with BCG: BCG is the most active treatment modality for superficial bladder cancer. In general, adding chemotherapy to BCG has not been successful. The results of a clinical trial conducted among patients with Stage I bladder cancer, however, suggest that the combination of BCG and electromotive mitomycin C (mitomycin delivered with the assistance of electric current) may be more effective than BCG alone. The addition of other biologic agents to BCG, such as interferon alpha, interleukin-2 and interleukin 12, is also being evaluated.

Gene Therapy: Currently, there are no gene therapies approved for the treatment of bladder cancer. Gene therapy is defined as the transfer of new genetic material into a cell for therapeutic benefit. This can be accomplished by replacing or inactivating a dysfunctional gene and/or replacing or adding a functional gene into a cell to make it function normally. Gene therapy has been directed towards the control of rapid growth of cancer cells, control of cancer cell death and efforts to facilitate immune-mediated death of cancer cells. Currently, a few gene therapy studies are being conducted in patients with refractory bladder cancer. If successful, these therapies could be applied to patients with earlier stages of bladder cancer.

Enhanced Delivery of   Mitomycin: Researchers have theorized that slowing down the production of urine and making urine more alkaline might enhance the results of adjuvant treatment with mitomycin. This is accomplished by restricting fluid intake, administering sodium bicarbonate and emptying the bladder more frequently with catheterization.

In a clinical trial, 230 patients with superficial bladder cancer were either treated with techniques that enhanced the concentration of mitomycin in the urine or with standard mitomycin and the results were then directly compared. Patients who received the enhanced concentrations of mitomycin developed recurrences in an average of 29 months, compared to 14 months for patients who received standard mitomycin treatment.

The researchers concluded that techniques that increase drug exposure in the bladder appear to improved standard treatment with intravesical mitomycin for superficial bladder cancer.

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Patients with Stage I bladder cancer have a cancer that invades the subepithelial connective tissue, but does not invade the muscle of the bladder and has not spread to lymph nodes. Stage I disease is classified as a "superficial" bladder cancer. A variety of factors ultimately influence a patient's decision to receive treatment of cancer. The purpose of receiving cancer treatment may be to improve symptoms through local control of the cancer, increase a patient's chance of cure, or prolong a patient's survival. The potential benefits of receiving cancer treatment must be carefully balanced with the potential risks of receiving cancer treatment.

The following is a general overview of the treatment of Stage I bladder cancer. Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied to your situation. The information on this Web site is intended to help educate you about your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.

Most new treatments are developed in clinical trials. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Participation in a clinical trial may offer access to better treatments and advance the existing knowledge about treatment of this cancer. Clinical trials are available for most stages of cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. To ensure that you are receiving the optimal treatment of your cancer, it is important to stay informed and follow the cancer news in order to learn about new treatments and the results of clinical trials.

Standard initial treatment for all patients with Stage I bladder cancer is a transurethral resection (TUR) with electrical (cautery) or laser thermal destruction of all visualized cancer. A TUR is an operation that is performed for both the diagnosis and management of bladder cancer. During a TUR, a urologist inserts a thin, lighted tube called a cystoscope into the bladder through the urethra to examine the lining of the bladder. The urologist can remove samples of tissue through this tube or can remove some or all of the cancer in the bladder.

Rarely, for more extensive or multiple superficial cancers, a segmental cystectomy (removal of part of the bladder) is necessary. Even more rarely, radical cystectomy (complete removal of the bladder) is used for extensive multiple superficial cancers. To learn more about TUR, go to Surgery for Bladder Cancer.

Surgery (TUR) alone is effective in preventing recurrences in approximately 50% of patients with superficial bladder cancer. Failure of treatment is usually due to the appearance of new superficial cancers, which can be retreated with TUR and cautery or laser therapies. Within 15 or 20 years, more than half of surviving patients will have experienced progressive cancer or, more commonly, will develop new cancers, including cancers of the upper urinary tract (ureters and renal pelvis). Approximately 20-30% of these cancers will require treatment with a cystectomy.

Because this is a cancer of older individuals, many patients will die of other causes before progression of bladder cancer. However, approximately 25% of patients treated for superficial bladder cancer will ultimately die of bladder cancer. Because the risk of developing invasive bladder cancer never goes away, it is important to have frequent follow-up examinations (cystoscopy) no matter what form of therapy is selected. It is extremely important to detect early progression because there are effective treatments for small advanced bladder cancers.

Bladder cancer frequently recurs, and it is important to develop strategies to prevent these recurrences. Adjuvant therapy is additional treatment that increases the effectiveness of a primary therapy. The goal of adjuvant therapy is to improve the chance of cure, prevent cancer from recurring or progressing to a worse stage, and/or improve the duration of overall survival. Adjuvant therapy for Stage I bladder cancer typically consists of immunotherapy and/or chemotherapy delivered directly into the bladder through the urethra (intravesical therapy).

Patients with Stage I bladder cancer are at risk not only for superficial cancer recurrences, but also for progression to more aggressive invasive bladder cancers. All patients with this stage of disease should consider adjuvant treatment.

Bladder instillation of Bacille Calmette-Guérin (BCG)

Bacille Calmette-Guérin (BCG) is one of the most common adjuvant therapies for treatment of superficial bladder cancer. BCG is an immunotherapy derived from a weakened form of the bacterium related to bacteria causing tuberculosis. BCG is instilled directly into the bladder through the urethra and exerts its anticancer effect by stimulating the body’s immune system to kill cancer cells. The primary side effects of BCG are pain in the bladder, blood in the urine and rarely, autoimmune disorders. Because BCG is a live bacteria, it may occasionally grow and cause an infection that requires antibiotic treatment.

Compared with treatment of superficial bladder cancer with TUR alone, treatment with TUR and intravesical BCG reduces the risk of recurrence and may also reduce the risk of cancer progression. However, even with optimal BCG therapy, almost half of all patients with superficial bladder cancer will ultimately have progression to invasive bladder cancer. This indicates the importance of frequent follow-up examinations (cystoscopy) to detect early progression to invasive cancer or new superficial cancers. Early invasive bladder cancer can be treated effectively.

Bladder Instillation of Chemotherapy

Instillation of chemotherapy drugs (mitomycin, thiotepa, or doxorubicin) into the bladder can reduce the incidence of superficial cancer recurrences, but no single drug has been confirmed to reduce progression of superficial cancer to invasive bladder cancer. This means that multiple small new cancers can be prevented but progression to a more invasive bladder cancer may occur despite treatment.

The optimal time to administer chemotherapy is immediately after TUR as the drugs might prevent reseeding of cancer cells disrupted with surgery. Mitomycin is probably the preferred drug because it produces few side effects and is not well absorbed into the system, which allows more of the drug to remain in the bladder to treat the cancer. Thiotepa is rapidly absorbed and produces low blood counts. Doxorubicin produces the most local side effects.

Strategies to Improve Treatment

The progress that has been made in the treatment of bladder cancer has resulted from improved surgical techniques, development of adjuvant treatments and doctor and patient participation in clinical studies. Future progress in the treatment of bladder cancer will result from continued participation in appropriate studies. Currently, there are several areas of active exploration aimed at improving the treatment of bladder cancer.

Supportive Care: Supportive care refers to treatments designed to prevent and control the side effects of cancer and its treatment. Side effects not only cause patients discomfort, but also may prevent the optimal delivery of therapy at its planned dose and schedule. In order to achieve optimal outcomes from treatment and improve quality of life, it is imperative that side effects resulting from cancer and its treatment are appropriately managed. For more information, go to Managing Side Effects.

Photodynamic Therapy: Photodynamic therapy combines a photosensitizer, such as Photofrin®, with red laser light to destroy cancer cells. The photosensitizer is injected into a vein, travels through the bloodstream and is picked up and incorporated into cancer cells. When the laser is directed at the cancer, the photosensitizer in the cancer cell captures the light from the laser, which kills the cell.

Photodynamic therapy was evaluated in 58 patients with resistant superficial bladder cancer (papillary and carcinoma in situ) who could not receive local treatment with chemotherapy or BCG immunotherapy. With a single photodynamic treatment, 84% of patients with residual resistant papillary transitional cell carcinoma and 75% of patients with refractory carcinoma in situ experienced a complete response or disappearance of all cancer. At four years from treatment, 59% of the patients responding to treatment were alive and 31 of 34 survived without cancer recurrence. Photodynamic therapy appears to be a safe and effective treatment for refractory carcinoma in situ or recurrent papillary transitional cell carcinoma. Clinical trials are ongoing to determine how best to utilize this form of treatment.

Combining Other Agents with BCG: BCG is the most active treatment modality for superficial bladder cancer. In general, adding chemotherapy to BCG has not been successful. The results of a clinical trial conducted among patients with Stage I bladder cancer, however, suggest that the combination of BCG and electromotive mitomycin C (mitomycin delivered with the assistance of electric current) may be more effective than BCG alone. The addition of other biologic agents to BCG, such as interferon alpha, interleukin-2 and interleukin 12, is also being evaluated.

Gene Therapy: Currently, there are no gene therapies approved for the treatment of bladder cancer. Gene therapy is defined as the transfer of new genetic material into a cell for therapeutic benefit. This can be accomplished by replacing or inactivating a dysfunctional gene and/or replacing or adding a functional gene into a cell to make it function normally. Gene therapy has been directed towards the control of rapid growth of cancer cells, control of cancer cell death and efforts to facilitate immune mediated death of cancer cells. Currently, a few gene therapy studies are being conducted in patients with refractory bladder cancer. If successful, these therapies could be applied to patients with earlier stages of bladder cancer.

Enhanced Delivery of Mitomycin: Researchers have theorized that slowing down the production of urine and making urine more alkaline might enhance the results of adjuvant treatment with mitomycin. This is accomplished by restricting fluid intake, administering sodium bicarbonate and emptying the bladder more frequently with catheterization.

In a clinical trial, 230 patients with superficial bladder cancer were either treated with techniques that enhanced the concentration of mitomycin in the urine or with standard mitomycin; the results were then directly compared. Patients who received the enhanced concentration of mitomycin developed recurrences in an average of 29 months, compared with 12 months for patients who received standard mitomycin treatment. 

The researchers concluded that techniques that increase drug exposure in the bladder appear to improve standard treatment with intravesical mitomycin for superficial bladder cancer.

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Patients with Stage II (T2) bladder cancer have cancer that invades through the connective tissue into the muscle wall, but has not spread outside the bladder wall or to local lymph nodes. Patients with cancer invading the inner half of the muscle of the bladder wall have a better outcome than patients with invasion into the deep muscle (outer half of the muscle of the bladder wall). Stage II bladder cancer is classified as a “deep” or “invasive” bladder cancer.

A variety of factors ultimately influence a patient’s decision to receive treatment of cancer. The purpose of receiving cancer treatment may be to improve symptoms through local control of the cancer, increase a patient’s chance of cure, or prolong a patient’s survival. The potential benefits of receiving cancer treatment must be carefully balanced with the potential risks of receiving cancer treatment.

The following is a general overview of the treatment of Stage II bladder cancer. Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied to your situation. The information on this Web site is intended to help educate you about your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.

Most new treatments are developed in clinical trials. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Participation in a clinical trial may offer access to better treatments and advance the existing knowledge about treatment of this cancer. Clinical trials are available for most stages of cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. To ensure that you are receiving the optimal treatment of your cancer, it is important to stay informed and follow the cancer news in order to learn about new treatments and the results of clinical trials.

There are essentially two ways to treat patients with Stage II (T2) bladder cancer: primary surgical treatment consisting of radical cystectomy with some form of urinary diversion or combined modality treatment consisting of administration of chemotherapy and/or radiation therapy, followed by radical cystectomy only for those patients who do not achieve a complete response. Patients who achieve a complete response following chemotherapy and/or radiation are followed closely and are treated with a radical cystectomy if cancer returns. It is important to realize that several physicians, including a urologist, a medical oncologist, and a radiation oncologist may be required to assist you in making the appropriate decision concerning the initial choice of treatment for Stage II bladder cancer.

The general health condition of the patient may help determine which approach to treatment is most appropriate. It is important to consider whether the patient is well enough to undergo radical cystectomy and creation of an artificial bladder. It is the general health condition, rather than age, that can be the limiting factor for this type of surgery. For patients in good condition, the choice will depend on the extent of cancer and the preferences of the patient and treating physicians.

Radical cystectomy is a standard treatment for Stage II bladder cancer. A radical cystectomy involves removal of the bladder, tissue around the bladder, the prostate, and seminal vesicles in men and the uterus, fallopian tubes, ovaries, anterior vaginal wall, and urethra in women. In addition, a radical cystectomy may or may not be accompanied by pelvic lymph node dissection. Radical cystectomy was once considered a procedure that seriously affected a patient's quality of life. With the creation of artificial bladders, referred to as continent reservoirs or "neobladders," that preserve voiding function, a radical cystectomy is now a far more acceptable procedure.

In some cases, Stage II bladder cancer may be controlled by transurethral resection (TUR) if the cancer is small enough and does not extend far into the bladder wall. A TUR is an operation that is performed for both the diagnosis and management of bladder cancer. During a TUR, a urologist inserts a thin, lighted tube called a cystoscope into the bladder through the urethra to examine the lining of the bladder. The urologist can remove samples of tissue through this tube or can remove some or all of the cancer in the bladder.

In addition, a segmental cystectomy (partial removal of the bladder) is also appropriate therapy in some patients with small cancers.

Approximately 50-80% of patients with Stage II bladder cancer are cured after undergoing a radical cystectomy. To learn more about TUR and cystectomy, go to Surgery for Bladder Cancer.

Following a radical cystectomy, local recurrence of cancer is uncommon because the cancer was removed. Despite undergoing complete removal of the bladder, however, some patients will still develop distant recurrences because undetected cancer cells called micrometastases spread to other locations in the body before the bladder was removed. Treatment with a systemic (whole-body) therapy such as chemotherapy may reduce or eliminate these micrometastases.

Neoadjuvant chemotherapy refers to chemotherapy that is given before surgery. The rationale behind neoadjuvant therapy for bladder cancer is twofold. First, pre-operative treatment can shrink some bladder cancers and therefore, may allow more complete surgical removal of the cancer. Second, because chemotherapy kills undetectable cancer cells in the body, it may help prevent the spread of cancer when used initially rather than waiting for patient recovery following the surgical procedure.

A study published in the New England Journal of Medicine reported that patients with muscle-invasive bladder cancer who received chemotherapy prior to cystectomy had better survival than patients treated with cystectomy alone. 

Over the past decade, there have been many clinical trials in the United States and Europe evaluating the combination of radiation and chemotherapy for initial treatment of patients with Stage II bladder cancer for the purpose of preserving the bladder. Bladder-preserving therapy is appealing because patients who achieve a complete response to treatment can often avoid additional treatment with a radical cystectomy unless they experience recurrence of their cancer.

In some clinical trials, approximately half or more of patients who were treated with bladder-preserving therapy (initial TUR of as much cancer as possible, plus chemotherapy and radiation therapy) survived cancer-free for three to four years after treatment. These results appear as good as those observed with radical cystectomy, but there have been no direct comparisons between bladder-preserving therapy and radical cystectomy. While bladder-preserving therapy has been widely adopted for the treatment of Stage II bladder cancer, some physicians still think it should be limited to clinical trials and not adopted as standard therapy.

Response rates with chemotherapy alone are likely to be lower than response rates with combined approaches to treatment, and treatment with chemotherapy alone remains investigational. 

Currently, the use of radiation therapy alone has been replaced by the use of radiation therapy and chemotherapy. However, there may be some patients who cannot tolerate chemotherapy, and radiation alone could be beneficial. To learn more, go to Radiation Therapy for Bladder Cancerr.

Questions to Ask Your Physician About the Treatment of Stage II Bladder Cancer

• What are the long-term results of treatment with radical cystectomy at the treating institution?
• What is the quality of life with the type of artificial bladder constructed at the treating institution?
• What are the long-term results of bladder-sparing treatments at the treating institution?

The progress that has been made in the treatment of bladder cancer has resulted from improved treatment developed in clinical trials. Future progress in the treatment of bladder cancer will result from continued participation in appropriate studies. Currently, there are several areas of active exploration aimed at improving the treatment of bladder cancer.

Supportive Care: Supportive care refers to treatments designed to prevent and control the side effects of cancer and its treatment. Side effects not only cause patients discomfort, but also may prevent the optimal delivery of therapy at its planned dose and schedule. In order to achieve optimal outcomes from treatment and improve quality of life, it is imperative that side effects resulting from cancer and its treatment are appropriately managed. For more information, go to Managing Side Effects.

Adjuvant Treatment After Surgery: It is important to realize that some patients with Stage II cancer already have small amounts of cancer that have spread away from the bladder. Undetectable areas of cancer are referred to as micrometastases and cannot be detected with any of the currently available tests. It is the presence of micrometastases that usually causes the relapses that follow treatment with a cystectomy alone.

Adjuvant therapy is a treatment that follows surgical cystectomy. In contrast to neoadjuvant chemotherapy, there is currently no proven benefit from receiving adjuvant chemotherapy and/or radiation therapy after surgery. Adjuvant chemotherapy is still being evaluated in clinical trials to prevent recurrence of bladder cancer. As new drug combinations are developed, it may be very important to participate in these clinical trials.

Chemotherapy Combined with Biologic Agents: Combining chemotherapy with biologic agents is the focus of intensive investigation.

Multiple Drug Resistance Inhibitors: Bladder cancer can be drug resistant at the outset of treatment. Drugs are being tested to determine if they will overcome or prevent the development of multiple drug resistance in bladder cancer.

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Overview

Patients with Stage III bladder cancer have cancer that invades through the connective tissue and muscle and into the immediate tissue outside the bladder and/or invades the prostate gland in males or the uterus and/or vagina in females. With Stage III bladder cancer, there is no spread to lymph nodes or distant sites. Stage III bladder cancer is classified as a “deep” or “invasive” bladder cancer. A variety of factors ultimately influence a patient’s decision to receive treatment of cancer. The purpose of receiving cancer treatment may be to improve symptoms through local control of the cancer, increase a patient’s chance of cure or prolong a patient’s survival. The potential benefits of receiving cancer treatment must be carefully balanced with the potential risks of receiving cancer treatment.

The following is a general overview of the treatment of Stage III bladder cancer. Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied to your situation. The information on this Web site is intended to help educate you about your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.

Most new treatments are developed in clinical trials. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Participation in a clinical trial may offer access to better treatments and advance the existing knowledge about treatment of this cancer. Clinical trials are available for most stages of cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. To ensure that you are receiving the optimal treatment of your cancer, it is important to stay informed and follow the cancer news in order to learn about new treatments and the results of clinical trials.

There are essentially two ways to treat patients with Stage III bladder cancer: primary surgical treatment consisting of radical cystectomy with some form of urinary diversion or combined modality treatment consisting of administration of chemotherapy and/or radiation therapy, followed by radical cystectomy only for those patients who do not achieve a complete response. Patients who achieve a complete response following chemotherapy are followed closely and are treated with a radical cystectomy if cancer returns. It is important to realize that several physicians, including a urologist, a medical oncologist and a radiation oncologist, may be required to assist you in making the appropriate decision concerning the initial choice of treatment for Stage III bladder cancer.

The general health condition of the patient may also help determine which approach to treatment is most appropriate. It is important to consider whether the patient is well enough to undergo radical cystectomy and creation of an artificial bladder. It is the general health condition, rather than age, that can be the limiting factor for this type of surgery. For patients in good condition, the choice will depend on the extent of cancer and the preferences of the patient and treating physicians.

Radical cystectomy is considered a standard treatment for Stage III bladder cancer. A radical cystectomy involves removal of the bladder, tissue around the bladder, the prostate and seminal vesicles in men and the uterus, fallopian tubes, ovaries, anterior vaginal wall and urethra in women. In addition, a radical cystectomy may or may not be accompanied by pelvic lymph node dissection.

Radical cystectomy was once considered a procedure that seriously affected a patient's quality of life. With the creation of artificial bladders, referred to as continent reservoirs or "neobladders," that preserve voiding function, a radical cystectomy is now a far more acceptable procedure.

To learn more about cystectomy, go to Surgery for Bladder Cancer.

Following a radical cystectomy, local recurrence of cancer is uncommon because the cancer was removed. Despite undergoing complete removal of the bladder, however, some patients will still develop distant recurrences because undetected cancer cells called micrometastases spread to other locations in the body before the bladder was removed. Treatment with a systemic (whole-body) therapy such as chemotherapy may reduce or eliminate these micrometastases.

Neoadjuvant chemotherapy refers to chemotherapy that is given before surgery. The rationale behind neoadjuvant therapy for bladder cancer is two-fold. First, pre-operative treatment can shrink some bladder cancers and therefore, may allow more complete surgical removal of the cancer. Second, because chemotherapy kills undetectable cancer cells in the body, it may help prevent the spread of cancer when used initially rather than waiting for patient recovery following the surgical procedure.

A study published in the New England Journal of Medicine reported that patients with muscle-invasive bladder cancer who received chemotherapy prior to cystectomy had better survival than patients treated with cystectomy alone. 

Over the past decade, there have been many studies in the United States and Europe evaluating the combination of radiation and chemotherapy for initial treatment of patients with Stage III bladder cancer for the purpose of preserving the bladder. Bladder-preserving therapy is appealing because patients who achieve a complete response to treatment can often avoid additional treatment with a radical cystectomy unless they experience recurrence of their cancer. In addition to avoiding a cystectomy, early treatment with chemotherapy may also kill bladder cancer cells that have already spread away from the bladder.

In some clinical trials, approximately half or more of patients who were treated with bladder-preserving therapy (initial TUR of as much cancer as possible, plus chemotherapy and radiation therapy) survived cancer-free for three to four years after treatment. These results appear as good as those observed with radical cystectomy, but there have been no direct comparisons of radical cystectomy to combination chemotherapy and radiation therapy without surgery. Furthermore, only selected patients with Stage III bladder cancer will be candidates for bladder-preserving therapy. As a result, some physicians think that bladder-preserving surgery should be limited to clinical trials and not adopted as standard therapy.

Chemotherapy without radiation therapy may be used for selected patients with inoperable stage III cancer, or for patients who cannot tolerate more extensive treatment.

Currently, the use of radiation therapy alone as a primary treatment for bladder cancer has largely been replaced by the combined use of radiation therapy and chemotherapy. However, there may be some patients who cannot tolerate chemotherapy and radiation alone is still beneficial. To learn more go to Radiation Therapy for Bladder Cancer.

• What are the long-term results of radical cystectomy at the treating institution?
• What is the quality of life with the type of artificial bladder constructed at the treating institution?
• What are the long-term results of bladder-sparing treatments at the treating institution?

The progress that has been made in the treatment of bladder cancer has resulted from improved treatment developed in clinical trials. Future progress in the treatment of bladder cancer will result from continued participation in appropriate studies. Currently, there are several areas of active exploration aimed at improving the treatment of bladder cancer.

Supportive Care: Supportive care refers to treatments designed to prevent and control the side effects of cancer and its treatment. Side effects not only cause patients discomfort, but also may prevent the optimal delivery of therapy at its planned dose and schedule. In order to achieve optimal outcomes from treatment and improve quality of life, it is imperative that side effects resulting from cancer and its treatment are appropriately managed. For more information, go to Managing Side Effects.

Adjuvant Treatment: It is important to realize that some patients with Stage III cancer already have small amounts of cancer that spread away from the bladder. Undetectable areas of cancer are referred to as micrometastases and cannot be detected with any of the currently available tests. It is the presence of micrometastases that usually causes the relapses that follow treatment with a cystectomy alone.

Adjuvant therapy is a treatment that follows surgical cystectomy. In contrast to neoadjuvant chemotherapy, there is currently no proven benefit from receiving adjuvant chemotherapy and/or radiation therapy after surgery. Adjuvant chemotherapy is still being evaluated in clinical trials to prevent recurrence of bladder cancer. As new drug combinations are developed, it may be very important to participate in these clinical trials.

Chemotherapy Combined with Biologic Agents: Combining chemotherapy with biologic agents is the focus of intensive investigation.

Multiple Drug Resistance Inhibitors: Bladder cancer can be drug resistant at the outset of treatment. Drugs are being tested to determine if they will overcome or prevent the development of multiple drug resistance in bladder cancer.

Gene Therapy: Currently, there are no gene therapies approved for the treatment of bladder cancer. Gene therapy is defined as the transfer of new genetic material into a cell for therapeutic benefit. This can be accomplished by replacing or inactivating a dysfunctional gene and/or replacing or adding a functional gene into a cell to make it function normally. Gene therapy has been directed towards the control of rapid growth of cancer cells, control of cancer cell death and efforts to facilitate immune mediated death of cancer cells. A few gene therapy studies are being carried out in patients with refractory bladder cancer. If successful, these therapies could be applied to patients with earlier stage disease.

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Patients with stage IV bladder cancer have cancer that has extended through the bladder wall and invaded the pelvic and/or abdominal wall and/or has lymph node involvement and/or spread to distant sites. Stage IV bladder cancer is also referred to as "metastatic" bladder cancer.

A variety of factors ultimately influence a patient’s decision to receive treatment of cancer. The purpose of receiving cancer treatment may be to improve symptoms through local control of the cancer, increase a patient’s chance of cure or prolong a patient’s survival. The potential benefits of receiving cancer treatment must be carefully balanced with the potential risks of receiving cancer treatment.

The following is a general overview of the treatment of stage IV bladder cancer. Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied to your situation. The information on this Web site is intended to help educate you about your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.

Most new treatments are developed in clinical trials. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Participation in a clinical trial may offer access to better treatments and advance the existing knowledge about treatment of this cancer. Clinical trials are available for most stages of cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. To ensure that you are receiving the optimal treatment of your cancer, it is important to stay informed and follow the cancer news in order to learn about new treatments and the results of clinical trials.

Currently, only a minority of patients with stage IV bladder cancer is cured following treatment with standard therapies. This is because most patients have cancer that has already spread outside the area of the pelvis. Because the majority of patients with stage IV bladder cancer have disease that has already spread and cannot be removed with surgery, treatment that can kill cancer cells throughout the body is necessary. Standard treatment consists of chemotherapy and occasionally surgery and radiation.

Some patients with bladder cancer have stage IV disease based only on the presence of local lymph node involvement and they have no evidence of distant spread of cancer. These patients with involvement of pelvic organs by direct extension and small volume metastasis to regional lymph nodes can be managed the same as stage III patients if all the cancer can be surgically removed by radical cystectomy and bilateral lymph node dissection. For more information about treatment of this type of stage IV bladder cancer click on Treatment of Stage III Bladder Cancer.

Before the development of effective chemotherapy, the average survival of patients with stage IV cancer was only 3-6 months from diagnosis. Bladder cancer, however, is sensitive to chemotherapy and may respond to treatment frequently and rapidly. Although long-term survival has been reported in some patients, chemotherapy is administered primarily to improve the symptoms of bladder cancer. Patients in good clinical condition should enter treatment with curative intent because some patients have prolonged remissions without cancer recurrences.

Combinations of chemotherapy agents are usually used for treatment of bladder cancer, as no single chemotherapy agent will produce a complete response in more than an occasional patient. Two commonly used chemotherapy regimens are GC and MVAC. GC is the combination of Gemzar® (gemcitabine) and cisplatin. MVAC is the combination of methotrexate, vinblastine, doxorubicin, and cisplatin. A phase III trial that compared these two regimens suggested that they were similarly effective, but that GC produced fewer side effects.

Radical cystectomy (removal of the bladder, tissue around the bladder, the prostate and seminal vesicles in men and the uterus, fallopian tubes, ovaries, anterior vaginal wall and urethra in women, with or without pelvic lymph node dissection) is sometimes recommended for treatment of patients with stage IV bladder cancer to control local spread and the complications this creates. Surgery is also utilized after an incomplete response of the primary cancer to radiation therapy and/or chemotherapy. To learn more about radical cystectomy, go to Surgery for Bladder Cancer.

The progress that has been made in the treatment of bladder cancer has resulted from improved treatments evaluated in clinical trials. Future progress in the treatment of bladder cancer will result from continued participation in appropriate studies. Currently, there are several areas of active exploration aimed at improving the treatment of bladder cancer.

Supportive Care: Supportive care refers to treatments designed to prevent and control the side effects of cancer and its treatment. Side effects not only cause patients discomfort, but also may prevent the optimal delivery of therapy at its planned dose and schedule. In order to achieve optimal outcomes from treatment and improve quality of life, it is imperative that side effects resulting from cancer and its treatment are appropriately managed. For more information, go to Managing Side Effects.

New Chemotherapy Regimens: Development of new multi-drug chemotherapy treatment regimens that incorporate new or additional anti-cancer therapies for use as treatment is an active area of clinical research carried out in phase II clinical trials. Questions of interest include the use of carboplatin in place of cisplatin in order reduce side effects, the combination of a taxane chemotherapy drug (such as paclitaxel) with cisplatin or carboplatin, and the addition of a third drug to gemcitabine and cisplatin.

Targeted Cancer Therapies: Targeted therapies are drugs interfere with specific pathways involved in cancer cell growth or survival. Some targeted therapies block growth signals from reaching cancer cells; others reduce the blood supply to cancer cells; and still others stimulate the immune system to recognize and attack the cancer cell. Depending on the specific “target”, targeted therapies may slow cancer cell growth or increase cancer cell death. Targeted therapies may be used in combination with other cancer treatments such as conventional chemotherapy.

Several different types of targeted therapy are being evaluated for the treatment of advanced bladder cancer. For example, a phase II clinical trial suggested that the targeted therapy Herceptin® (trastuzumab; a drug used to treat breast cancers that overexpress a protein known as HER2) may be effective in combination with chemotherapy for patients with HER2-positive advanced bladder cancer.

Phase I Trials: New anti-cancer therapies continue to be developed and evaluated in phase I clinical trials. The purpose of phase I trials is to evaluate new drugs and/or therapeutic approaches in order to determine the best way of administering the treatment and whether the treatment has any anti-cancer activity in patients with bladder cancer.

Multiple Drug Resistance Inhibitors: Bladder cancer can be drug resistant at the outset of treatment or develop drug resistance after treatment. Several drugs are being tested to determine if they will overcome or prevent the development of multiple drug resistance in bladder cancer and other cancers.

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Patients with recurrent bladder cancer have cancer that has returned following initial treatment with surgery, radiation, chemotherapy or immunotherapy.

A variety of factors ultimately influence a patient’s decision to receive treatment of cancer. The purpose of receiving cancer treatment may be to improve symptoms through local control of the cancer, increase a patient’s chance of cure, or prolong a patient’s survival. The potential benefits of receiving cancer treatment must be carefully balanced with the potential risks of receiving cancer treatment.

The following is a general overview of the treatment of recurrent bladder cancer. Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied to your situation. The information on this Web site is intended to help educate you about your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.

Most new treatments are developed in clinical trials. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Participation in a clinical trial may offer access to better treatments and advance the existing knowledge about treatment of this cancer. Clinical trials are available for most stages of cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. To ensure that you are receiving the optimal treatment of your cancer, it is important to stay informed and follow the cancer news in order to learn about new treatments and the results of clinical trials.

Patients with a diagnosis of superficial bladder cancer have frequent recurrences of cancer throughout their lives. Most of the time, these recurrences are non-invasive and not life threatening. Treatment of recurrent superficial bladder cancer essentially uses the same treatment approaches as were initially offered. Go to Stage I to learn about treatment options. In some instances, partial or total bladder resection may be utilized to control recurrent superficial bladder cancers. To learn more, go to Surgery for Bladder Cancer.

Approximately 20-40% of all patients with superficial bladder cancer will ultimately progress to more advanced stages or muscle invasive bladder cancer. When this occurs, patients are treated based on new staging of the current more invasive bladder cancer. For treatment of patients with superficial bladder cancer who have progressed, select one of the following:

Patients who experience a recurrence after initial treatment for stage II-IV bladder cancer may be treated with cystectomy (if not performed previously), chemotherapy, radiation therapy, or enrollment in a clinical trial,

The progress that has been made in the treatment of bladder cancer has resulted from improved treatments evaluated in clinical trials. Future progress in the treatment of bladder cancer will result from continued participation in appropriate studies. Currently, there are several areas of active exploration aimed at improving the treatment of bladder cancer.

Supportive Care: Supportive care refers to treatments designed to prevent and control the side effects of cancer and its treatment. Side effects not only cause patients discomfort, but also may prevent the optimal delivery of therapy at its planned dose and schedule. In order to achieve optimal outcomes from treatment and improve quality of life, it is imperative that side effects resulting from cancer and its treatment are appropriately managed. For more information, go to Managing Side Effects.

New Chemotherapy Regimens: Development of new multi-drug chemotherapy treatment regimens that incorporate new or additional anti-cancer therapies for use as treatment is an active area of clinical research carried out in phase II clinical trials.

Targeted Cancer Therapies: Targeted therapies are drugs interfere with specific pathways involved in cancer cell growth or survival. Some targeted therapies block growth signals from reaching cancer cells; others reduce the blood supply to cancer cells; and still others stimulate the immune system to recognize and attack the cancer cell. Depending on the specific “target”, targeted therapies may slow cancer cell growth or increase cancer cell death. Targeted therapies may be used in combination with other cancer treatments such as conventional chemotherapy.

Several different types of targeted therapy are being evaluated for the treatment of advanced bladder cancer. For example, a phase II clinical trial suggested that the targeted therapy Herceptin® (trastuzumab; a drug used to treat breast cancers that overexpress a protein known as HER2) may be effective in combination with chemotherapy for patients with HER2-positive advanced bladder cancer.

Phase I Trials: New anti-cancer therapies continue to be developed and evaluated in phase I clinical trials. The purpose of phase I trials is to evaluate new drugs and/or therapeutic approaches in order to determine the best way of administering the treatment and whether the treatment has any anti-cancer activity in patients with bladder cancer.

Multiple Drug Resistance Inhibitors: Bladder cancer can be drug resistant at the outset of treatment or develop drug resistance after treatment. Several drugs are being tested to determine if they will overcome or prevent the development of multiple drug resistance in bladder cancer and other cancers.

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The optimal treatment of bladder cancer may require involvement of several different physicians, including a urologist, medical oncologist and/or radiation oncologist. Medical oncologists are specialists in the management of cancer and use of anti-cancer treatments such as chemotherapy. Radiation oncologists are specialists in the use of radiation to treat cancer and urologists are surgeons and experts in the management of cancers involving the urinary system. There are several different surgical procedures that are performed by urologists for the diagnosis and treatment of the different stages of bladder cancer.

A transurethral resection (TUR) is an operation that is performed for both the diagnosis and management of bladder cancer. During a TUR, a urologist inserts a thin, lighted tube called a cystoscope into the bladder through the urethra to examine the lining of the bladder. The urologist can remove samples of tissue through this tube or can remove some or all of the cancer in the bladder. The urologist can also use electrical (cautery or fulguration) or laser thermal destruction of stage 0-I superficial bladder cancers. A TUR causes few problems, although patients may have some blood in their urine and difficulty or pain when urinating for a few days afterward.

TUR is used to treat patients with superficial bladder cancers (non-invasive papillary carcinoma and carcinoma in situ). Repeated TURs are frequently performed throughout the life of patients with superficial bladder cancers. At the time of TUR, chemotherapy agents and biological agents, such as BCG, are often instilled into the bladder. Surgeons can also cauterize (electrical heat) or apply a laser for heat to kill visualized superficial cancers during a TUR.

TUR can also be utilized to remove all or a part of stage II-III bladder cancer in patients scheduled to receive chemotherapy and radiation therapy for bladder-sparing therapy approaches.

A radical cystectomy consists of the surgical removal of the bladder as well as the tissue and some of the organs around it. For men, the prostate and the seminal vesicles, and possibly the urethra, are often removed. For women, the uterus, ovaries, fallopian tubes, part of the vagina, and the urethra are often removed. A pelvic lymph node dissection, removal of the lymph nodes in the pelvis, may also be performed to determine whether the cancer has spread to these lymph nodes. Pelvic lymph node dissection adds little to the overall side effects of radical cystectomy, improves staging accuracy and may be curative in some patients with minimal lymph node involvement.

Because the bladder is removed, doctors must design an alternate way for the body to store and pass urine. This is often referred to as a urinary diversion technique and is described in complete detail below in the section entitled “Creation of Alternative Bladders and Neobladders.” Radical cystectomy with preservation of sexual function can be performed in some men and new forms of urinary diversion can eliminate the need for an external urinary appliance.

A segmental or partial cystectomy is an operation during which a portion of the bladder is removed and the ends are sewn back together. It is sometimes performed for treatment of patients with multiple superficial cancers or large superficial cancers in an attempt to avoid removing the entire bladder. However, there are very few situations where this is done.

The application of segmental or partial cystectomy to the treatment of invasive bladder cancer remains controversial. In selected cases with small cancers, the results may be similar to those observed after radical cystectomy. However, the potential for development of cancer in the remaining bladder is still present.

After segmental cystectomy, patients may not be able to hold as much urine in their bladder. In most cases, this problem is temporary; however, some patients may have long-lasting changes in bladder capacity.

Because surgical treatment of bladder cancer removes the bladder, doctors must design an alternate way for the body to store and pass urine. This is often referred to as a urinary diversion technique. Sometimes, this involves using part of the intestine to construct a tube that carries urine from the ureters to an opening (called a stoma) to the outside of the body. The procedure to construct this stoma is called an ostomy or urostomy. Many researchers have also been studying more permanent ways to allow urine to be stored and passed to help improve urinary function and quality of life. This often involves creating a substitute bladder, sometimes called a neobladder.

The construction of a neobladder involves the use of a segment of the intestine between the ileum (last part of the small intestine) or colon (part of the large intestine) to form a new bladder, referred to as an ileocolonic neobladder. The ureters, which deliver urine from the kidneys to the bladder, are attached to one end of the neobladder. Urine collects in the storage pouch and empties into a stoma (opening in the abdominal wall) through the abdomen to a collection bag. Whenever possible, the neobladder is connected to the urethra and voiding can be more natural.

The use of an intestinal neobladder is an extremely effective form of continent diversion. Complete day and night continence can be achieved in approximately 80% patients. Mild to moderate stress incontinence occurs in 10% of patients and severe stress incontinence in 5%. Patients older than 70 years are more likely to have trouble with continence than younger patients. However, in one retrospective analysis from a single institution, elderly patients (70 years of age or older) in good general health were found to have similar clinical and functional results following radical cystectomy as younger patients. This is an important observation because it suggests that medical condition is more important than age for outcome of surgery.

The progress that has been made in the treatment of bladder cancer has resulted from improved treatment developed in clinical trials. Future progress in the treatment of bladder cancer will result from patients and doctors continuing to participate in appropriate studies.

Supportive Care: Supportive care refers to treatments designed to prevent and control the side effects of cancer and its treatment. Side effects not only cause patients discomfort, but also may prevent the optimal delivery of therapy at its planned dose and schedule. In order to achieve optimal outcomes from treatment and improve quality of life, it is imperative that side effects resulting from cancer and its treatment are appropriately managed. For more information, go to Managing SideEffects

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Radiation therapy may be an integral part of the treatment of bladder cancer. However, since cancer of the bladder is not exclusively treated with radiation therapy, it may be important for patients to be treated at a medical center that can offer multi-modality treatment involving medical oncologists, radiation oncologists, and surgeons.

Radiation therapy or radiotherapy uses high-energy rays to damage or kill cancer cells by preventing them from growing and dividing. Similar to surgery, radiation therapy is a local treatment used to eliminate or eradicate cancer that can be encompassed within a radiation field. Radiation therapy is not typically useful in eradicating cancer cells that have already spread to other parts of the body. Radiation therapy may be externally or internally delivered. External radiation delivers high-energy rays directly to the cancer from a machine outside the body. Internal radiation, or brachytherapy, involves the implantation of a small amount of radioactive material in or near the cancer. Currently the use of radiation therapy alone as a primary treatment for bladder cancer has largely been replaced by the combined use of radiation therapy and chemotherapy. The main use of radiation therapy is in combination with chemotherapy for treatment of patients with stage II-III disease or recurrent cancer. However, radical cystectomy remains the primary modality for the treatment of stages II and III bladder cancer.

Over the past decade, many clinical trials in the United States and Europe have evaluated the combination of radiation and chemotherapy as initial treatment of patients with stage II-III bladder cancer for the purpose of preserving the bladder. Bladder-preserving therapy is appealing because patients who achieved a complete response to treatment can often avoid surgical removal of the cancer unless they experience recurrence of their cancer. In addition to helping patients avoid cystectomy, early treatment with chemotherapy may also kill cancer cells that have already spread away from the bladder.

In some clinical trials, approximately half or more of patients who were treated with bladder-preserving therapy (initial TUR of as much cancer as possible, plus chemotherapy and radiation therapy) survived cancer-free three to four years after treatment. Although these results appear as good as those observed with surgery (radical cystectomy), there have been no direct comparisons of radical cystectomy to combination chemotherapy and radiation therapy. While bladder-preserving therapy has been widely adopted for the treatment of stage II-III bladder cancer, some physicians still think it should be limited to clinical trials and not adopted as standard therapy.

The goal of palliative therapy is to decrease the symptoms of cancer, such as pain, in order to improve a patient's quality of life. For some patients with advanced bladder cancer, radiation therapy may be used to shrink the cancer and relieve cancer symptoms.

Modern radiation therapy for bladder cancer is administered via machines called linear accelerators, which produce high energy external radiation beams that penetrate the tissues and deliver the radiation dose deep into the areas where the cancer resides. These modern machines and other state-of-the-art techniques have enabled radiation oncologists to significantly reduce side effects, while improving the ability to deliver a curative radiation dose to cancer-containing areas and minimizing the radiation dose to normal tissue. For example, with modern radiation therapy, skin burns almost never occur, unless the skin is being deliberately targeted or because of unusual patient anatomy or extension of the cancer close to the source.

After an initial consultation with a radiation oncologist, the next session is usually a planning session, which is called a simulation. During this session, the radiation treatment fields and most of the treatment planning are determined. Of all the visits to the radiation oncology facility, the simulation session may actually take the most time. During simulation, patients lay on a table somewhat similar to that used for a CT scan. The table can be raised and lowered and rotated around a central axis. The "simulator" machine is a machine whose dimensions and movements closely match that of an actual linear accelerator. Rather than delivering radiation treatment, the simulator lets the radiation oncologist and technologists see the area to be treated. The room is periodically darkened while the treatment fields are being set and temporary marks may be made on the patient's skin with markers. The radiation oncologist is aided by one or more radiation technologists and often a dosimetrist, who performs calculations necessary in the treatment planning. The simulation may last anywhere from 15 minutes to an hour or more, depending on the complexity of what is being planned.

Once the aspects of the treatment fields are satisfactorily set, x-rays representing the treatment fields are taken. In most centers, the patient is given multiple tattoos which mark the treatment fields and replace the marks previously made with markers. These tattoos are not elaborate and consist of no more than pinpricks followed by ink, appearing like a small freckle. Tattoos enable the radiation technologists to set up the treatment fields each day with precision, while allowing the patient to wash and bathe without worrying about obscuring the treatment fields. Radiation treatment is usually given in another room separate from the simulation room. The treatment plans and treatment fields resulting from the simulation session are transferred over to the treatment room, which contains a linear accelerator focused on a patient table similar to the one in the simulation room. The treatment plan is verified and treatment started only after the radiation oncologist and technologists have rechecked the treatment field and calculations and are thoroughly satisfied with the setup.

The majority of patients are able to complete radiation therapy for bladder cancer without significant difficulty. Side effects and potential complications of radiation therapy are limited to the areas that are receiving treatment with radiation. The chance of a patient experiencing side effects, however, is highly variable. A dose that causes side effects in one patient may cause no side effects in other patients. If side effects occur, the patient should inform the technologists and radiation oncologist because treatment for these side effects is almost always available and effective.

Radiation therapy to the abdominal/pelvic area may cause diarrhea, abdominal cramping, or increased frequency of bowel movements or urination. These symptoms are usually temporary and resolve once the radiation is completed. Occasionally abdominal cramping may be accompanied by nausea.

Blood counts can be affected by radiation therapy. In particular, the white blood cell and platelet counts may be decreased. This is dependent on how much bone marrow is in the treatment field and whether the patient has previously received or is receiving chemotherapy. These changes in cell counts are usually insignificant and resolve once the radiation is completed. However, many radiation therapy institutions make it a policy to check the blood counts at least once during the radiation treatments.

It is not unusual for some patients to note changes in sleep or rest patterns during the time they are receiving radiation therapy and some patients will describe a sense of tiredness and fatigue.

Late complications are infrequent following radiation treatment of bladder cancer. Potential complications do include bowel obstruction, ulcers or cancers caused by the radiation. The probabilities of these late complications are also affected by previous extensive abdominal or pelvic surgery, radiation therapy and/or concurrent chemotherapy.

The progress that has been made in the treatment of bladder cancer has resulted from improvements in multi-modality treatment and doctor and patient participation in clinical studies. Future progress in the treatment of bladder cancer will result from continued participation in appropriate studies.

Supportive Care: Supportive care refers to treatments designed to prevent and control the side effects of cancer and its treatment. Side effects not only cause patients discomfort, but also may prevent the optimal delivery of therapy at its planned dose and schedule. In order to achieve optimal outcomes from treatment and improve quality of life, it is imperative that side effects resulting from cancer and its treatment are appropriately managed. For more information, go to Managing Side Effects.

References