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.
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. 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.
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. To learn more about radical cystectomy, go to Surgery for Bladder Cancer.
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.
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.
von der Maase H, Hansen SW, Robers JY et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. Journal of Clinical Oncology. 2000;18:3068-77.
von der Maase H, Sengelov L, Roberts JT et al. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. Journal of Clinical Oncology. 2005;20:4602-8.
 Iaffaioli RV, Milano A, Caponigro F. Therapy of metastatic bladder cancer. Annals of Oncology. 2007;18 (supplement 6): vi153-vi156.
Hussain MHA, MacVicar GR, Petrylak DP et al. Trastuzumab, paclitaxel, carboplatin, and gemcitabine in advanced human epidermal growth factor receptor-2/neu-positive urothelial carcinoma: results of a multicenter phase II National Cancer Institute Trial. Journal of Clinical Oncology. 2007;25:2218-2224.