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.

Chemotherapy Treatment of Stage IV 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. Platinol® chemotherapy has historically been considered to be the most active agent, followed by methotrexate, Velban®, doxorubicin or cyclophosphamide. More recent clinical studies suggest that some newer chemotherapy agents including paclitaxel and Gemzar® may be as effective as methotrexate, Velban®, doxorubicin or cyclophosphamide (MVAC).

Various combinations and schedules of Platinol®, methotrexate, Velban®, doxorubicin and/or cyclophosphamide have been evaluated over the past 10-15 years. Complete response rates range from 14% to 20% and partial responses range from 46-57%. The most commonly used treatment regimen, MVAC, produces complete responses in approximately 20% of patients and these responses last an average of 38 months.

A recent clinical trial suggests the combination of Gemzar®/Platinol® is as effective against transitional cell carcinoma of the urothelium as MVAC, but with fewer side effects. Researchers from 19 countries treated 396 patients who had metastatic bladder cancer with either MVAC or Gemzar®/Platinol® chemotherapy. The researchers then directly compared the overall survival, response rates to treatment, the time it took for the disease to progress, side effects and quality of life among the two treatment groups. The results indicated that overall survival between patients receiving MVAC and those receiving Gemzar®/Platinol® was similar; however, the Gemzar®/Platinol® therapy was better tolerated and resulted in fewer side effects. These findings suggest that the Gemzar®/Platinol® combination is an effective treatment option for metastatic stage IV bladder cancer because it appears to produce fewer side effects than the more commonly used MVAC regimen. The researchers concluded that Gemzar®/Platinol® should be considered a new standard treatment.

In other diseases, another chemotherapy agent, Paraplatin®, has been compared to Platinol® and found to have fewer side effects and similar anti-cancer activity. Because of the reduced side effects, more recent studies have supported the use of Paraplatin® combined with newer drugs, such as paclitaxel and Gemzar®. The combination of Paraplatin® and paclitaxel has been evaluated in newly diagnosed patients with metastatic bladder cancer. The complete response rate following treatment with Paraplatin®/paclitaxel was reported to be 40%, while the partial response rate was 25% and 15% of patients had stable disease.

Surgery for Stage IV Bladder Cancer

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.

Strategies to Improve Treatment

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.