Metastatic Bladder Cancer

Urothelial cancer (also called transitional cell carcinoma) is the most common type of bladder cancer. The standard initial (or first-line) treatment for metastatic urothelial cancer is chemotherapy, using a combination of anti-cancer drugs based on Cisplatin, the most common drug used in the treatment of metastatic bladder cancer.

Cisplatin is a platinum-based drug that kills cancer cells by damaging their DNA and stopping them from dividing. Depending on the dosage, Cisplatin can affect the nerves, inner ear and kidneys.

You’re eligible for this type of chemotherapy if you’re medically fit. Being considered medically fit involves assessment of various factors, including:

· Kidney function

· Heart function

· Performance status (a score that estimates your ability to perform certain activities of daily living without the help of others)

· Hearing capacity

· Existing peripheral neuropathy (peripheral neuropathy is a type of nerve damage that usually causes pain, numbness or tingling in the fingers and toes, but can progress up the limbs to involve the feet and legs, hands and arms)

· Other factors your medical team may consider important

Fifty percent of people with advanced urothelial cancer are not eligible for Cisplatin-based chemotherapy, so alternative treatment options are considered.

These can include combinations using Carboplatin, or nonplatinum-based drugs, such as gemcitabine, docetaxel or paclitaxel. In patients who are not eligible for Cisplatin, immunotherapy may be beneficial, but this requires further study and is not yet approved in this setting in Canada.

Side effects of Chemotherapy

Some common side effects of chemotherapy include fatigue, increased risk of infection and bleeding; hearing problems; bowel changes; decreased kidney function; peripheral nerve damage, tingling and numbness (neuropathy), hair thinning or loss; skin rash; weight changes; anemia (low red blood cell counts); and thrombocytopenia (low platelets resulting in risk of bleeding).

There is also a small risk of developing clots in the blood vessels. Nausea and vomiting can occur with chemotherapy, however there are very good supportive medications to help with this and these symptoms are usually very well controlled.

Your cancer care team will review these side effects prior to starting chemotherapy. You should contact your cancer care team if you’re experiencing these side effects. However, you should seek immediate help for urgent concerns including having a fever (ask your medical team how they define “fever” in this situation), signs and symptoms of an allergic reaction, unresolved nausea, vomiting and diarrhea and any signs of bleeding.

When initial treatment doesn't work

Although many patients will respond to the initial treatments we’ve been discussing, it doesn’t work in all patients. In some patients, the disease may eventually progress after initial therapy and secondary (“second-line” or additional) therapy could then be offered.

Immunotherapy as a secondary treatment might be offered to you if the diseasehas progressed, despite receiving platinum-based chemotherapy. (See section on immunotherapy for more details.)

Secondary chemotherapy would be offered to you if you are not a candidate for immunotherapy or for those of you whose bladder cancer progresses during or after immunotherapy. No single second-line chemotherapy treatment plan is considered to be the standard secondary therapy, so your oncologist will discuss plans with you.

Immunotherapy for Bladder Cancer

Immunotherapy stimulates the body’s defenses to attack and kill cancer cells. There are two types of immunotherapy used to treat bladder cancer:

Cancer Vaccines – Bacillus Calmette–Guérin (BCG) vaccine is given intravesically (into the bladder via the urethra) to treat nonmuscle-invasive (superficial) bladder cancer. It is a live bacterium that attracts immune cells, which then attack cancer cells.
Immune Checkpoint Inhibitors –This type of immunotherapy works by stimulating the immune system, allowing immune cells to attack cancer cells. Immune checkpoint inhibitors are types of drugs that block certain proteins on the surface of some types of immune cells, such as T cells, and some cancer cells.

These proteins help keep immune responses in check and can keep T cells from killing cancer cells. When these proteins are blocked, the “brakes” on the immune system are released and T cells are able to kill cancer cells better.

These drugs are given intravenously, typically every two to four weeks. Research into and clinical trials of immunotherapy drugs and approvals for their use in Canada is ongoing.

Please discuss with your oncologist which immunotherapy drugs are currently available and which ones your oncologist uses. Your healthcare team will consider your personal needs to plan the drugs, doses and schedules of immunotherapy.

Side effects of Immunotherapy

Side effects of these drugs can include fatigue, loss of appetite, an allergic reaction, skin rashes and itchy skin. Since these medications work by removing the “brakes” on the body’s immune system, they can also cause inflammation of any normal tissue in the body. This is because the immune system can start attacking other parts of the body, which can cause serious or even life-threatening problems in the lungs, intestines, liver, hormone-making glands or other organs.

It’s very important to promptly report any new side effects to your health care team, both during or after treatment with immune checkpoint inhibitors. If serious side effects do occur, treatment may need to be held or stopped and you may be provided with high doses of corticosteroids (man-made drugs that closely resemble cortisol, a hormone that your adrenal glands produce naturally) to suppress your immune system.

Prompt recognition and treatment of these side effects may lessen the severity and duration overall, so it’s important to report any new or unusual side effects to your care team as soon as possible.

Immunotherapy may not be recommended for all patients. Immunotherapy may also be used in combination with other treatments, such as surgery, radiation or chemotherapy. This use is currently limited to clinical trials.

Radiotherapy

Radiotherapy can be offered to manage your metastatic bladder cancer. This can be offered for a variety of reasons, including alleviating pain when the cancer has spread to the bones (bone metastases) and reduction in urinary symptoms or bleedin

Treatment of bone metastases

You may be offered bisphosphonates if you have bone metastases. Bisphosphonates are a type (or class) of drugs that prevent the loss of bone density and play an important role in management of bone metastases.

This treatment reduces skeletal-related events (such as fractures and spinal cord compression), manages increased calcium levels in the body, and also manages pain related to bone-metastases.

Important

Diagnosis of metastatic bladder cancer can be challenging. It’s vital that you ask for support and maintain a healthy lifestyle.

Regular exercise is important and recommended at every stage of your treatment. It reduces cancer and treatment-related fatigue and improves quality of life.

To manage side effects from treatment it’s also essential that you eat well during your treatment. Try to limit alcoholic drinks, red meat, processed foods and increase your intake of plant-based foods including fruits, vegetables and legumes.

If you experience treatment related side effects, such as poor appetite, taste changes, dry mouth, difficulty chewing or swallowing, consult your health care provider and registered dietitian at your cancer care centre for advice.

Certain substances in foods and medications can interfere with chemotherapy or immunotherapy. Talk to your oncologist or pharmacist before starting your chemotherapy and immunotherapy. Do not start a new medication or supplement prior to consulting your oncologist while you are on these treatments.

Immunotherapy and Clinical Trials

As immunotherapy for the treatment of bladder cancer is relatively new, some treatments may be approved by Health Canada, but may not yet be covered by your provincial or private drug program. Others may only be available through a clinical trial or a patient access program.