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Stage 4 Bladder Cancer


Patients with stage IV bladder cancer have cancer that has spread 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.


The following is a general guide of the treatment of stage IV bladder cancer. Your cancer will ultimately influence the treatments that are right for your situation. The information on this web-site is intended to help inform you about possible treatment options and to create discussion with your treating cancer physician.


Because most 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


Bladder cancer 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.


Methods 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 best delivery of therapy at its planned dose and schedule. 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.


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.


Immunotherapy for Bladder Cancer


Immunotherapy is the use of medicines to help a person’s own immune system recognize and destroy cancer cells. This type of treatment is sometimes used to treat bladder cancer.


Intravesical BCG

BCG is a type of bacteria related to the one that causes tuberculosis. While it doesn’t usually cause a person to get sick, it can help trigger an immune response. BCG can be put right into the bladder as a liquid. This activates immune system cells in the bladder, which then attack bladder cancer cells.


Immune checkpoint inhibitors

An important part of the immune system is its ability to keep itself from attacking normal cells in the body. To do this, it uses “checkpoints” – proteins on immune cells that need to be turned on (or off) to start an immune response.


Cancer cells sometimes use these checkpoints to keep from being attacked by the immune system. But newer drugs that target these checkpoints, called checkpoint inhibitors, can help restore the immune response against cancer cells.


PD-1 and PD-L1 inhibitors

Atezolizumab (Tecentriq) and avelumab (Bavencio) are drugs that target PD-L1, a protein on cells (including some cancer cells) that helps keep the immune system from attacking them. By blocking PD-L1, these drugs boost the immune system's response against the cancer cells. This can shrink some tumors or slow their growth.


Nivolumab (Opdivo) and pembrolizumab (Keytruda) target PD-1, a protein on certain immune cells (called T cells) that normally helps keep these cells from attacking other cells in the body. Blocking PD-1 can allow the immune system to attack the cancer cells, which can shrink some tumors or slow their growth.


These drugs can be used in different situations to treat bladder cancer:


• Any of these checkpoint inhibitors can be used in people with advanced bladder cancer that starts growing again after chemotherapy.

• Atezolizumab and pembrolizumab can be used in people who can't get the chemo drug cisplatin (due to things like hearing loss, kidney failure, or heart failure).

• Avelumab can be used as an additional (maintenance) treatment in people with advanced bladder cancer that did not get worse during their initial chemotherapy treatments.

• Pembrolizumab can be used to treat certain bladder cancers that are not growing into the muscle wall of the bladder, are not getting smaller with intravesical BCG, and are not being treated with a cysectomy.

These drugs are given as intravenous (IV) infusions, usually every 2 to 6 weeks, depending on the drug.


Clinical Trials:


New anti-cancer therapies continue to be developed and evaluated in clinical trials. There are three phases of clinical trials before approval.  See our clinical trials section for more information.


Managing Liver Metastases


When bladder cancer spreads to the liver, it doesn’t always cause symptoms. It may be picked up by liver function tests, which are blood tests that measure certain levels of enzymes and proteins in the blood. Abnormal levels can indicate liver disease or damage.


If liver metastasis causes symptoms, they can include:


• pain or discomfort in the mid-section

• fatigue and weakness

• weight loss/poor appetite

• fever

• bloating

• swelling in the legs

• a yellow tint to the skin or the whites of the eyes


In addition to liver function tests, doctors use imaging tests to diagnose liver metastases. These may include MRI (magnetic resonance imaging), CT scan (computed tomography), ultrasound, and/or PET scan (positron emission tomography). Sometimes, a combined PET/CT scan is used.


Your doctor also may recommend getting a sample of the suspicious area(s) for examination under a microscope (biopsy). He or she may involve an interventional radiologist to obtain precise and minimally invasive imaging.


The most common treatments for metastatic bladder cancer in any location (bone, brain, lung, or liver) are systemic medications, which treat cancer throughout the entire body. Systemic medications include chemotherapy, targeted therapies, and clinical trials that have already been discussed.  Liver directed therapies, including surgery, may be an option.


Liver Directed Therapies: There are numerous liver directed therapies available for those who are faced with a Stage 4 cervical 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 the liver tumors. These liver directed therapies may include chemoembolization, cryoablation, cyberknife, hepatic arterial infusion, liver resection, proton beam therapy, radioembolization or SIRT, radiofrequency ablation, or SBRT.  You can learn more on our treatment page under liver directed therapies.










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