How Does the Treatment Work?

Chemotherapy uses chemicals to fight cancer. Radiology uses radiation to kill cancer cells. Immunotherapy, on the other hand, is trying to use your own immune system to fight cancer.

Bladder cancer is known to have many mutations or have specific types of mutations. These changes allow immunotherapy drugs to do their job of treating the cancer. That is why immunotherapy may help bladder cancer patients. It is used most often with late-stage cancers. As more research happens, better treatments will evolve.

Many active immunotherapies have been approved by the FDA to treat late stage cancers (including skin cancer and cancers of the lung, bladder, kidney, prostate and blood). The approved immunotherapy agents for bladder cancer are:

  • Atezolizumab (Tecentriq®)
  • Durvalumab (Imfinzi) 
  • Avelumab (Bavencio) 
  • Nivolumab (Opdivo®) 
  • Pembrolizumab (Keytruda®)
  • BCG (Bacillus Calmette-Guérin)

Many more immunotherapies and combinations are being tested in clinical trials. Clinical Trials are research studies that study a new drug or treatment. They help doctors learn the best ways to treat patients. They are done in phases to see if a new approach is safe and works well. Every drug or treatment approved by the U.S. Food and Drug Administration (FDA) must go through clinical trials first.

This is an exciting time for patients. Scientists are gaining insight into our genetic codes and the genetic codes of cancers. We're in a time of rapid growth towards personalized care.

Advances are quickly moving to find life-saving therapies.

What Immunotherapy Treatments are Used for Bladder Cancer or Other Urologic Cancers?

BCG

Bacillus Calmette-Guérin or BCG, is an immunotherapy used to treat some bladder cancers (mainly cancers that stay in the bladder). BCG treatment has been around for 40 years. Still, doctors don't know why it works well for some people but not others. 

BCG is a weakened form of the tuberculosis bacteria. It is placed straight into the bladder as a liquid (an "intravesical" treatment). BCG treatment involves using a small tube to place the BCG mixture into the bladder. This is repeated weekly for six weeks. BCG causes the immune system to act against cancer cells in the bladder. It can be very helpful in treating non-muscle invasive bladder cancer (before it has grown deep into the tissue). It is also being studied in other types of cancer. 

Non-muscle invasive BCG refractory bladder cancer doesn't seem to react to immunotherapy. Many clinical trials are testing if immune checkpoint inhibitors (another immunotherapy) can activate a response for these patients.

Immune Checkpoint Inhibitors

There are signals on cells that stop immune cells from attacking normal tissue. These signals are called checkpoints. Healthy cells use these checkpoints to slow down or stop an immune attack. Cancer cells can also use these checkpoints to hide from an immune system response.

Immune Checkpoint Inhibitors are drugs that can block the checkpoints on the surface of cancer cells. This prevents them from being able to hide from the immune system. When these checkpoints are blocked, T cells (the immune system's killer cells) can find and attack the cancer. Examples of checkpoint proteins found on T cells or cancer cells include PD-1/PD-L1 and CTLA-4.

The immunotherapies approved for bladder cancer are all immune checkpoint inhibitors. Most of these treatments are given by IV every two or three weeks. They aim to help a person's immune system fight the cancer.

The immune checkpoint inhibitors used for bladder cancer at this time are:

  • Atezolizumab (Tecentriq), durvalumab (Imfinzi) and avelumab (Bavencio). These are drugs that target PD-L1 on some cancer cells to stop the cells from hiding. They boost the immune response against the cancer cells. This can shrink some tumors or slow their growth.
  • Nivolumab (Opdivo) and pembrolizumab (Keytruda). These drugs target PD-1, another protein that normally helps keep the immune system in check. Blocking PD-1 can help the immune system attack the cancer cells. This can shrink some tumors or slow their growth.

There's been a huge growth in clinical trials for these drugs. A main focus is for treating advanced bladder cancer

When is the Best Time to Use an Immunotherapy?

  • BCG is mainly used to treat patients with non-muscle invasive bladder cancer. 
  • Checkpoint inhibitors are offered to late stage or metastatic patients at this time. 
  • Immunotherapy is a good option for stage III or IV bladder cancer patients who can't have a major operation. 
  • Patients who can't handle chemotherapy (because of other health problems) may benefit from immunotherapy.
  • People with advanced bladder cancer that returns, or grows again after chemotherapy may opt for immunotherapy. 
  • Some clinical trials are giving immunotherapy to patients earlier in the process (at the time of surgery, for example). 
  • You can ask your doctor if immunotherapy or a clinical trial would be helpful to you.

Benefits and Risks of Immunotherapy

Each treatment option usually comes with both benefits and risks/side effects. For BCG, fluid is placed straight into the bladder. So, most side effects are bladder-related. For example: a person might need to use the bathroom more often, urgently and maybe with pain. Those side effects tend to go away after treatment ends.

Your healthcare provider will check to make sure there's no blood or infection in your urine. If you have signs of infection, BCG is stopped and the infection is treated.

Compared to other systemic or IV treatments, BCG tends to have less risks. Most people handle the side effects very well. Many patients feel nothing. Still, feeling tired is a common side effect.

Among advanced bladder cancer patients, immune checkpoint inhibitors have been found to help extend life. This is compared with chemotherapy in some settings. If the cancer itself is causing pain and the treatment shrinks tumors, patients may feel better. However, at this time, most cases of advanced bladder cancer do not respond to immune checkpoint inhibitors. Further clinical trials with new and combinations of treatments are needed.

Patients with autoimmune diseases may not be good candidates for checkpoint inhibitors. Autoimmune diseases may include ulcerative colitis, rheumatic arthritis, lupus or others. These are health issues where the immune system attacks healthy tissue. These drugs may also cause autoimmune diseases, including thyroid problems or diabetes. This doesn't mean a patient has to stop treatment, but it is a factor.

Some patients develop inflammation in the lungs (pneumonitis), in the liver (hepatitis) or in the colon (colitis). The standard way to manage such side effects with treatment is to use steroids to slow down the immune response. Sometimes steroid replacement will also be used to address adrenal problems.

Most of the time, people handle checkpoint inhibitors very well. For most patients, the benefits of these treatments outweigh the problems.

Who is a Good Candidate for Immunotherapy?

The best candidates for BCG often have intermediate or high risk non-muscle invasive bladder cancer. Doctors will consider the:

  • Size and number of tumors
  • Aggressive nature of the tumor
  • Grade of the tumor(s) (high grade is more aggressive)
  • If tumors have recurred
  • Overall health of the patient

Good candidates for BCG most often get the treatment once per week for six weeks. If they respond well, they get maintenance therapy. This means they get three doses every six months for up to three years.

A good candidate for immune checkpoint inhibitors (intravenous immunotherapy) is someone who is well enough to get more treatment after chemotherapy. Bladder cancer can be aggressive, so the earlier patients can be treated with immunotherapy, the better. Once a patient is too sick, it may not be helpful.

Because immunotherapy revs-up the immune system, the people who do best are not at risk for autoimmune diseases.
If a patient doesn't respond to first treatments, they may be a good candidate for a clinical trial.