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Bladder Cancer


Stage IV bladder cancer occurs when bladder cancer has moved beyond the bladder wall and invaded the pelvic and/or abdominal wall and/or has lymph node involvement and/or spread to distant sites such as the liver, lungs, or bone. Stage IV bladder cancer is also called “metastatic” bladder cancer.


Many factors influence the decision to receive cancer treatment. The purpose of receiving cancer treatment may be to improve symptoms through local control of the cancer, increase the chance of cure or prolong to prolong 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 are unique in every situation and prognostic factors may influence how these general treatment principles are applied to each situation. The information shared here is intended to help educate about treatment options and to help create a mutual or shared decision-making process with individual treatment teams in mind.


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 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 cancer treatment, it is important to stay informed and follow the cancer news in order to learn about new treatments and the results of clinical trials.


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 may be beneficial for stage IV bladder cancer. Although long-term survival has been reported in some patients, chemotherapy is administered primarily to improve the symptoms of bladder cancer.


Combinations of chemotherapy agents are usually used for treatment of bladder cancer, as no single chemotherapy agent will usually produce a complete response. 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 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.


Other methods of managing Stage IV 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 that 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.


Liver Directed Therapies:  There are numerous liver directed therapies available for those who are facing a Stage IV Bladder Cancer diagnosis with liver metastases or bladder cancer that has spread to the liver.  These therapies are dependent on the size, number and location of liver tumors.



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.




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