Immunotherapy for bladder cancer

Immunotherapy helps to strengthen or restore the immune system's ability to fight cancer. This works to kill cancer cells and stop cancer cells from growing and spreading.

Some people with bladder cancer have immunotherapy. If you have immunotherapy, your healthcare team will use what they know about the cancer and about your health to plan the drugs, doses and schedules.

Immunotherapy may be the only treatment you have or it may be used along with other treatments. You may have immunotherapy to:

• kill bladder cancer cells
• strengthen your immune system
• stop bladder cancer cells from growing and spreading
• lower the risk that the cancer will come back (recur)
• help keep the cancer from coming back after it has already been treated (called maintenance therapy)
• control symptoms of bladder cancer

Intravesical immunotherapy is when the drug is placed directly into the bladder. The doctor passes a tube (catheter) through the urethra and into the bladder. An immunotherapy drug is given through the tube into the bladder. The drug is left in the bladder for 1 to 2 hours to give it time to work.

Bacillus Calmette-Guérin (BCG) is the most common drug used for intravesical immunotherapy. It is the same bacteria used to vaccinate against tuberculosis. It contains live, but weak, bacteria that gets your immune system to kill cancer cells in the bladder.

Intravesical BCG may be used to treat stage 0 and stage 1 bladder cancers that are classified as intermediate risk or high risk. It is given after a transurethral resection of bladder tumour (TURBT), once a week for 6 weeks (called induction therapy). To lower the risk of side effects, treatment with intravesical BCG is usually started a few weeks after a TURBT.

If there is no cancer remaining after the 6 weeks, more treatment is often given as maintenance therapy. Intravesical BCG is given once a week for 3 weeks every 3 to 6 months for up to 3 years.

If cancer still remains after the 6 weeks, another 6 weeks of intravesical BCG is usually offered.

Intravesical BCG is also used to treat bladder cancer that comes back only in the inner lining of the bladder.

Nadofaragene firadenovec (Adstiladrin) is another type of intravesical immunotherapy. It contains a virus that has been changed in the lab so it cannot reproduce in the body. The virus carries a gene that makes a protein called interferon alfa-2b, which helps the immune system. Once the drug is put into the bladder, the gene enters the bladder cells. These cells then make interferon alfa-2b proteins that help your immune system kill cancer cells in the bladder. Nadofaragene firadenovec is also known as a type of gene therapy.

Nadofaragene firadenovec may be used to treat carcinoma in situ, high-risk, non-muscle-invasive bladder cancer. It’s offered only after BCG has been given but doesn’t work. Nadofaragene firadenovec is usually given every 3 months. How long it’s used depends on how well the cancer responds to treatment and the side effects you have.

Immune checkpoint inhibitors are a type of immunotherapy that uses drugs called monoclonal antibodies. The immune system normally stops itself from attacking normal cells in the body by using specific proteins called checkpoints, which are made by some immune system cells. Bladder cancer cells sometimes use these checkpoints to avoid being attacked by the immune system. Immune checkpoint inhibitors block the checkpoint proteins so immune system cells (called T cells) can attack and kill the cancer cells.

An immune checkpoint inhibitor may be offered for locally advanced or metastatic bladder cancer that:

• is still growing during or after chemotherapy that includes the drug cisplatin
• comes back within 12 months of finishing chemotherapy
• canʼt be treated with chemotherapy
• has a high risk of coming back after surgery
• will be removed with surgery after neoadjuvant therapy with gemcitabine and cisplatin

An immune checkpoint inhibitor is most often used alone, but may be combined with chemotherapy. It can be used as a maintenance therapy after chemotherapy.

The immune checkpoint inhibitors used for bladder cancer target the PD-1 or PD-L1 checkpoint protein. They are:

• pembrolizumab (Keytruda) – most commonly used
• nivolumab (Opdivo)
• durvalumab (Imfinzi)
• avelumab (Bavencio)

The drug is given through a needle into a vein (intravenous infusion) once every 2 or 3 weeks until the disease progresses or the side effects outweigh the benefits of having the treatment.

Enfortumab vedotin (Padcev) is a type of monoclonal antibody. You may be offered enfortumab vedotin if you have already been treated with cisplatin or carboplatin and a PD-1 or PD-L1 immune checkpoint inhibitor. It may also be offered if you can't be treated with cisplatin or carboplatin.

Side effects can happen with any type of treatment for bladder cancer, but everyone’s experience is different. Some people have many side effects. Other people have few or none at all.

Side effects of immunotherapy will depend mainly on the type of drug, the dose, how it’s given and your overall health.

Intravesical BCG and nadofaragene firadenovec may cause these side effects:

• a need to urinate (pee) more often than usual (frequent urination)
• an intense need to urinate (urgent urination)
• burning during urination
• flu-like symptoms, such as fever, chills, fatigue and an achy body
• loss of appetite

Immune checkpoint inhibitors or monoclonal antibodies may cause these side effects:

• fatigue
• diarrhea
• skin problems, such as a rash, dry skin and itching
• nausea and vomiting
• loss of appetite
• low blood cell counts
• lung problems, such as cough and difficulty breathing
• inflammation of any organ (called an immune-related adverse event)
• numbing of the hands and feet (peripheral neuropathy)
• hair loss

You will have blood tests frequently to check how your body is reacting to immunotherapy. If you have inflammation, your doctor may give you steroids.

Be sure to report side effects to the healthcare team. Side effects can happen any time during, immediately after or a few days or weeks after immunotherapy. Sometimes late side effects develop months or years later. Most side effects go away on their own or can be treated, but some side effects may last a long time or become permanent.

Your healthcare team is there to help. The sooner you tell them of any problems, the sooner they can suggest ways to help you deal with them.

All drugs, including those used to treat cancer, are approved for use in Canada by Health Canada. If a drug is mentioned on cancer.ca, it means that Health Canada has approved the drug and pharmaceutical companies sell it in Canada. It does not mean that the drug is offered everywhere in Canada.

Paying for drugs is the responsibility of provincial and territorial health departments. Each health department makes its own decisions about which drugs to cover (pay for) in that province or territory. This means that a drug may be covered in one province, but not in others.

Your oncologist will talk to you about different drug treatments and what is available through your provincial or territorial drug program.

Details on specific drugs change regularly. Find out more about sources of drug information and where to get details on specific drugs.

Find out more about immunotherapy. To make the decisions that are right for you, ask your healthcare team questions about immunotherapy.