Immunotherapy involves training the body’s own immune defenses to recognize and eliminate cancer cells, offering an alternative or complement to chemotherapy and radiation. For bladder cancer, this approach has become an increasingly important part of cancer treatment, with two main paths depending on how advanced the disease is: intravesical Bacillus Calmette-Guérin (BCG) therapy for non-muscle invasive cases, and immune checkpoint inhibitors for advanced or metastatic disease.
Immunotherapy for Bladder Cancer
What is Immunotherapy?
Immunotherapy is a type of cancer treatment that stimulates the body’s own defenses – the immune system – to fight bladder cancer. The immune system is made up of white blood cells and organs and tissues of the lymph system that the body uses to fight infections and other diseases.
Immunotherapy for bladder cancer can be used 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
What Immunotherapy Treatments are Used for Bladder Cancer?
Two main types are used: intravesical BCG therapy, delivered directly into the bladder, and immune checkpoint inhibitors, delivered intravenously.
BCG Treatment
Bacillus Calmette–Guérin (BCG) is a type of treatment that is given intravesically (directly into the bladder via the urethra) to treat non-muscle invasive bladder cancer (NMIBC). It is a live bacterium that attracts immune cells, which then attack cancer cells. Since BCG is administered intravesically the anticancer effects are local and side effects are primarily local as well.
BCG is typically given as a course of weekly treatments for 6 weeks, sometimes followed by maintenance treatments for up to 3 years. To administer the BCG for bladder cancer therapy, the doctor passes a tube (catheter) through the urethra and into the bladder. An immunotherapy drug is given through the tube into the bladder and is left in the bladder for approximately 2 hours.
Benefits of BCG:
- This is a relatively non-invasive treatment process.
- It can help you save your bladder and prevent the spread of cancer cells to other parts of your body.
- It does not require any other medications to work effectively.
- It stimulates the immune system to attack cancer cells without attacking healthy cells.
Immune Checkpoint Inhibitors
This type of immunotherapy for bladder cancer works by stimulating the immune system, allowing immune cells to attack cancer cells. Immune checkpoint proteins sit on the surface of some types of immune cells, especially T cells, and some cancer cells. These proteins help keep immune responses in check and can keep T cells from killing cancer cells.
Cancer cells express such proteins to blunt the human immune system to react against the cancer. When these proteins are blocked with immune checkpoint inhibitors, 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 six weeks. This is an active area of research and many clinical trials related to immune checkpoint inhibitors are still ongoing. As a result, approvals for use of these drugs in Canada are constantly evolving.
When are Immune Checkpoint Inhibitors Used?
An immune checkpoint inhibitor may be offered as a second-line therapy for advanced or metastatic bladder cancer that:
- is still growing during or after chemotherapy that includes cisplatin
- comes back within 12 months of finishing chemotherapy
Types of Immune Checkpoint Inhibitors
The immune checkpoint inhibitors used for bladder cancer target the PD-1 or PD-L1 checkpoint protein. They are:
- Pembrolizumab (Keytruda) – most commonly used
- Durvalumab (Imfinzi)
- Atezolizumab (Tecentriq)
- Avelumab (Bavencio) – may be used as a maintenance therapy after chemotherapy
- Nivolumab (Opdivo) – may be used after bladder removal surgery for high-risk bladder cancer
Please discuss with your oncologist which immunotherapy drugs for bladder cancer are currently available and which ones are recommended. Your healthcare team will consider your personal needs to plan the drugs, doses and schedules of immunotherapy.
What are Side Effects of Immunotherapy for Bladder Cancer?
Side Effects of BCG Therapy
With intravesical BCG therapy for bladder cancer, the physician administers a liquid drug directly into your bladder, rather than orally or through injection into the bloodstream, which may lead to the following immunotherapy 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
Most BCG side effects are mild to moderate. If any severe reactions occur, such as pain, inflammation, or bleeding, be sure to contact a medical professional immediately.
Side Effects of Immune Checkpoint Inhibitors
Unlike BCG, currently available immune checkpoint inhibitors are given systemically (intravenously to circulate throughout the body). Bladder cancer 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 (e.g. arthritis, colitis, pneumonitis). The immune system may 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.
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
It is very important to promptly report any new bladder cancer immunotherapy side effects to your health care team, both during and after treatment with immune checkpoint inhibitors. If serious side effects do occur, the immunotherapy may need to be held or stopped and you may be treated with 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 bladder cancer immunotherapy side effects are critical and may lessen the severity and duration of the side effects.
Additional Considerations and Ongoing Research
Immunotherapy for bladder cancer may not be recommended for all patients, especially for those with pre-existing autoimmune conditions. Immunotherapy may also be used in combination with other treatments, such as surgery, radiation, or chemotherapy. Many new immunotherapies for bladder cancer are currently being investigated in clinical trials.
Navigating Bladder Cancer with Bladder Cancer Canada
Bladder Cancer Canada is the first and only patient advocacy organization in Canada dedicated to bladder cancer. Facing bladder cancer is undoubtedly a challenging journey, but with the support of the Bladder Cancer Canada community, you can find the strength and knowledge to navigate it more confidently.
Whether you’re starting treatment, managing side effects, or supporting a loved one through treatment, you don’t have to work through it alone. We connect patients and caregivers with support groups and one-to-one peer support from people who’ve been through it.
Contact us for more information on Immunotherapy for Bladder Cancer.