Immunotherapy for bladder cancer

Overview

Immunotherapy for bladder cancer is treatment that helps the immune system recognize and attack bladder cancer cells. You also may hear it called immune therapy.

You may receive immunotherapy directly into your bladder through a thin tube called a catheter. You can also receive it through a vein.

Treatment depends on the type and stage of bladder cancer. Most bladder cancers are a type called urothelial carcinoma. This is cancer that starts in urothelial cells that line the inside of the bladder.

Immunotherapy is not the same as chemotherapy.

• Chemotherapy works by stopping or slowing the growth of cancer cells, which grow and divide quickly.
• Immunotherapy helps the immune system find and attack cancer cells.

In bladder cancer, chemotherapy and immunotherapy may be used separately or together. Immunotherapy also may be used with an antibody-drug conjugate. An antibody is a protein that can recognize and attach to a specific target on a cell. An antibody-drug conjugate is a type of medicine that uses an antibody to carry a cancer-killing drug. The antibody targets specific proteins on the surface of cancer cells and delivers the drug to those cells.

Types

The main types of immunotherapy used for bladder cancer include:

• Immune checkpoint inhibitors. These medicines block signals that cancer cells can use to hide from the immune system. Examples include pembrolizumab, nivolumab, avelumab and durvalumab. These medicines help the immune system recognize and attack cancer cells.

  Immune checkpoint inhibitors usually are given through a vein so they can travel through the bloodstream and throughout the body. They may be used for some high-risk cancers that have not spread. High-risk bladder cancer has features that make it more likely to come back or grow into deeper layers of the bladder. Immune checkpoint inhibitors also may be used for advanced or metastatic urothelial cancer. Metastatic cancer is cancer that has spread to other parts of the body.

• Intravesical bacillus Calmette-Guerin (BCG). Intravesical means that the treatment is put directly into the bladder through a thin tube called a catheter. BCG is commonly used after removal of a non-muscle invasive bladder tumor. Non-muscle invasive bladder cancer is cancer that has not grown into the muscle layer of the bladder wall. BCG can lower the chance that high-risk cancer will come back or grow into the bladder muscle.
• BCG-based combination immunotherapy. Some high-risk non-muscle invasive bladder cancers can be treated with BCG plus another immune treatment. Examples include:
  • Durvalumab. This immune checkpoint inhibitor may be used with BCG for high-risk cancer that has not yet been treated with BCG.
  • Nogapendekin alfa inbakicept-pmln (Anktiva). This medicine stimulates the immune system. It activates certain immune cells that help the immune system attack cancer cells. It may be used with BCG for some cancers that do not respond to BCG.

Why it's done

Immunotherapy may be part of treatment for non-muscle invasive, muscle-invasive, locally advanced or metastatic bladder cancer. The goal of treatment may be to:

• Lower the chance that cancer will come back.
• Help preserve the bladder.
• Support treatment with surgery.
• Control cancer that cannot be removed or has spread.

Non-muscle invasive bladder cancer

Non-muscle invasive bladder cancer is cancer that has not grown into the muscle layer of the bladder wall.

A procedure called transurethral resection of bladder tumor (TURBT) removes the bladder tumor through the urethra. The urethra is the tube that carries urine from the bladder out of the body. After TURBT, you may receive BCG to lower the chance that the cancer will come back or grow into the bladder muscle. BCG is a standard immunotherapy for many people with high-risk disease and for some people with intermediate-risk disease.

For high-risk non-muscle invasive bladder cancer that has not been treated with BCG, durvalumab can be used with BCG.

For high-risk non-muscle invasive bladder cancers that do not respond to BCG, other treatments may be used. Some people have BCG-unresponsive non-muscle invasive bladder cancer with carcinoma in situ (CIS). CIS is a high-grade bladder cancer that is limited to the bladder lining. This type of cancer may occur with or without tumors that grow in the bladder on the bladder lining. Treatment options may include nogapendekin alfa inbakicept-pmln (Anktiva) with BCG or pembrolizumab.

The treatment choice depends on factors such as the size, number and location of tumors and whether CIS is present. High-grade bladder cancer is more likely to come back, grow into the bladder muscle or spread to other parts of the body. The choice of treatment also depends on how well previous BCG treatment worked, whether your care team recommends bladder removal surgery and your preferences.

Muscle-invasive bladder cancer

Muscle-invasive bladder cancer is cancer that has grown into the muscle layer of the bladder wall. Immunotherapy may be used before and after surgery.

Before surgery, you may get durvalumab with two chemotherapy medicines, gemcitabine and cisplatin. After surgery, you may get durvalumab on its own.

You may get pembrolizumab with the antibody-drug conjugate enfortumab vedotin before and after bladder removal surgery, also called cystectomy. You may get this combination whether or not you can receive cisplatin.

Some people with high-risk muscle-invasive urothelial cancer may receive nivolumab, an immune checkpoint inhibitor, after surgery to lower the chance that cancer will come back.

Locally advanced or metastatic bladder cancer

Locally advanced bladder cancer is cancer that has grown outside the bladder into nearby tissues or lymph nodes. Metastatic bladder cancer is cancer that has spread to distant parts of the body.

Enfortumab vedotin plus pembrolizumab may be one of the first treatments used for locally advanced or metastatic urothelial cancer that has not been treated with systemic medicine. Systemic medicine is medicine that travels through the bloodstream throughout the body.

Nivolumab is an immune checkpoint inhibitor. It may be given with the chemotherapy medicines gemcitabine and cisplatin.

If your cancer has not grown or spread after chemotherapy, you may get the immune checkpoint inhibitor avelumab after chemotherapy to help control the cancer.

Your care team considers your kidney function, heart health, nerve health and overall health when deciding whether cisplatin is an option. The team also considers your hearing. Cisplatin can damage your kidneys, nerves and hearing, so having health conditions in these areas may make cisplatin unsuitable for you.

Risks

The risks of immunotherapy for bladder cancer depend on the type of immunotherapy and any other medicines your care team gives with it. Side effects can happen during treatment or after treatment ends.

Intravesical BCG and BCG-based treatment

BCG commonly causes temporary bladder irritation and flu-like symptoms. You may have burning with urination, an urgent need to urinate, more-frequent urination, blood in your urine, fatigue, chills or a mild fever. Serious BCG infection is not common but can happen and may require urgent treatment.

Immune checkpoint inhibitors

Immune checkpoint inhibitors can cause side effects that happen when the immune system attacks healthy tissues. This can lead to inflammation in the skin, thyroid gland, intestines, liver, lungs or kidneys. Some immune-related side effects can be serious or life-threatening. Some side effects need to be treated right away.

Contact your care team right away if you have any of these side effects:

• A new or worsening rash.
• A new or worsening cough or shortness of breath.
• Severe diarrhea or stomach pain.
• Yellowing of the skin or eyes.
• Changes in how much you urinate.
• Tiredness that is severe or not usual.
• Dizziness or fainting.
• Confusion.

Combination treatment

When you get pembrolizumab with enfortumab vedotin, side effects can come from either medicine. They can include severe skin reactions, nerve damage called peripheral neuropathy, high blood sugar and lung inflammation.

Tell your care team right away if you have:

• A new or worsening rash, blistering or peeling skin.
• A new or worsening cough, shortness of breath or trouble breathing.
• New or worsening numbness or tingling in your hands or feet.
• Muscle weakness.
• Increased thirst.
• Frequent urination.
• New or worsening vision changes.
• Confusion.

Your care team may pause treatment or lower the dose of enfortumab vedotin. The team also may use medicines called corticosteroids to treat serious immune-related side effects.

Contact your care team right away if you have:

• New or worsening shortness of breath.
• Severe diarrhea.
• Yellowing of the skin or eyes.
• A severe rash.
• Confusion.
• Fainting.
• A fever that does not go away.

Also contact your care team right away if you have other symptoms that worry you. Serious immune reactions and BCG infection can worsen quickly if treatment is delayed.

How you prepare

Before giving immunotherapy, your care team reviews your cancer treatment history, medicines and other health conditions. Tell your care team if you have an autoimmune disease. An autoimmune disease is a condition in which the immune system wrongly attacks healthy cells or tissues in the body. Also tell your care team if you have had an organ transplant or a bone marrow transplant, if you take medicines that affect the immune system, or if you may be pregnant or have an infection.

If you are receiving treatment through a vein, you may have blood tests during treatment to check how organs such as the liver, kidneys and thyroid are working. These tests can help your care team find signs of immune-related side effects early.

If you are receiving BCG or another treatment directly in your bladder, your care team may check for a urinary tract infection or bleeding. The team may delay your treatment if your bladder or urinary tract needs time to heal.

What you can expect

Before treatment

Your care team explains which immunotherapy you are receiving, whether it is given alone or with another cancer treatment and how often you receive it. Treatment schedules vary by medicine and by the stage of bladder cancer.

• Systemic immunotherapy travels through the bloodstream throughout the body. It usually is given through a vein.
• Intravesical immunotherapy goes directly into the bladder through a catheter.

During intravesical immunotherapy

A healthcare professional places a thin catheter through your urethra into your bladder and gives the immunotherapy through the catheter. Then the catheter is removed. For BCG, you usually have the medicine in your bladder for about two hours before urinating it out. Your care team gives you instructions for using the bathroom safely after BCG because your urine can contain live BCG bacteria for several hours after treatment.

During intravenous immunotherapy

A healthcare professional places an IV in your vein and gives the medicine slowly through the IV over a set amount of time. If your treatment includes chemotherapy or enfortumab vedotin, you may receive those medicines on the same day or on different days during your treatment.

After treatment

After treatment, your care team tells you which symptoms to expect and which symptoms require that you call for help right away.

You may receive treatment for weeks, months or longer, depending on the medicine, the stage of your cancer, how well the immunotherapy works and any side effects. Your care team may delay or stop treatment because of an infection or treatment-related side effects.

Results

How your care team checks whether immunotherapy is working depends on the type of bladder cancer you have.

• For non-muscle invasive bladder cancer, follow-up commonly includes one or more of these procedures or tests to see whether your cancer has come back, grown or spread:
  • Urine cytology. This test looks for cancer cells in urine.
  • Cystoscopy. This procedure uses a thin scope to look inside the bladder.
  • Biopsy. A biopsy is a procedure in which a small tissue sample is removed for testing.
  • Transurethral resection of bladder tumor (TURBT). This procedure removes the bladder tumor through the urethra. The urethra is the tube that carries urine from the bladder out of the body. You may need TURBT if your care team sees tissue that may be cancer.
• For muscle-invasive bladder cancer treated before surgery, the tissue removed during surgery is checked for living cancer cells. If no living cancer cells are found, this is called a pathological complete response. This means that the cancer has responded well to treatment. It does not mean that the cancer will not come back.
• For locally advanced or metastatic bladder cancer, imaging tests such as a CT scan may be done at regular intervals to see whether the treatment is working. The scans can show whether tumors have gotten smaller, stayed about the same size or grown.

Immunotherapy does not work for everyone. Some people have long-lasting cancer control, but others don't benefit. If the cancer grows or spreads, your care team may recommend a different treatment or a clinical trial.

A clinical trial for bladder cancer is a research study involving people with the condition. These studies help researchers learn more about how to treat the cancer. Clinical trials may test new treatments or new ways of using existing treatments. Joining a clinical trial may give you access to a treatment or an approach that is not otherwise available.

Clinical trials have risks, and there is no guarantee that the treatment being studied will help you. What researchers learn may help improve treatment for people with bladder cancer in the future. Talk with your care team about clinical trials.

Clinical trials

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