Immune System and Cancer

What is the Immune System and How Does it Work with Cancer?

The immune system is a natural part of our body. Its role is to get rid of foreign or damaged material and cells before they cause trouble. 

Most of the time, our immune system can find foreign invaders like bacteria and viruses, and destroy them. The immune system uses signals to attack them while leaving healthy cells alone.

Cancer is different from an illness caused by a bacteria or virus. It involves the uncontrolled growth of normal body cells. In other words, cancer cells may not be found by the immune system. Though they look different under the microscope, cancer cells can hide and grow. One way cancer cells hide is to express proteins on their surface to turn-on a "checkpoint" to stop an immune system attack.

The National Cancer Institute (NCI) studied common tumors in its Cancer Genome Atlas project. The research showed that bladder cancer, skin cancer and lung cancer have the most cellular changes (mutations). These types of cancer may be more likely to respond to treatments that help the immune system find cancer cells, called "immunotherapies".

What is Immunotherapy?

Immunotherapy is any treatment that makes the immune system stronger. For cancer, it helps the body find and attack cancer cells. The field of immuno-oncology studies how the immune system interacts with cancer. It uses that information to make new treatments.

Treatments like chemotherapy and radiation work differently. They try to kill growing cancer cells directly. Immunotherapies, on the other hand, block the signals (or "checkpoints"), and rev-up immune cells to attack or control cancer. These therapies make changes to our immune system in order to attack cancer.

What Happens Under Normal Conditions?

Your immune system is a network of cells, tissues and organs. They work together to recognize and kill invaders in your body.
The immune system protects us because it can tell the difference between self and non-self. "Self" means our own body tissues. "Non-self" means any odd cell or invader, like bacteria, viruses, parasites and fungus. Normally, our immune system will not attack a cell that it sees as "self".

What Happens When Cancer Cells Grow and Hide?

Cancer cells are tricky for the immune system. They come from our own cells. As they grow and spread, cancer cells change or mutate to look less and less like normal cells. Sometimes our immune system can sense these changes and react. Other times, the cancer cells can hide so they can grow.

Three things help cancers hide from the immune system:

  1. Antigenicity: An antigen is a special type of protein that is recognized by the immune system. Cancer cells may not have the right type or number of antigens to be recognized.
  2. Immunogenicity: Some cancer cells use signals to stop the immune system from an attack.
  3. The patient themselves: Some patients' immune systems react better than others to control cancer.

Key Statistics

  • 80,470 people in the U.S. will be diagnosed with bladder cancer this year. 
  • 50% or more patients with non-muscle invasive bladder cancer (NMIBC) can get advanced disease. Immunotherapy could be helpful. 
  • More than 50% of advanced or metastatic bladder cancer patients can't take standard chemotherapy, or chemo doesn't work for their cancer. Immunotherapy or a clinical trial in immunotherapy may be the best choice.
  • 90% of eligible patients don't know about or aren't considered for clinical trials. These patients may be helped from an immunotherapy trial. 

Hundreds of new immunotherapy treatments are being tested for cancer. While a small percentage of people have had success with new treatments so far, this research offers a great hope for the future.

Treatment

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.

After Treatment

Cancer treatments for metastatic cancer are often used to extend life, not to cure the cancer. Unfortunately, treatment doesn't work for all people. Many of these advanced cancers come back or progress. Each patient is different, so you'll want to make a follow-up plan with your doctor after treatment.

A worthy goal is often to try to feel better, longer. You can do things that make you feel healthier like eating well, exercising daily stop smoking and reducing stress.

Patients who get immunotherapy can often resume their life, to include work and exercise. Feeling tired is often a problem at first. The good news is that this often goes away soon after treatment ends. With advanced cancer, people don't feel very well and sometimes treatment can make them feel better.

Are There Long-term Side Effects?

Each person has a different course of treatment so responses are different for everyone. Immunotherapy, by itself, most often brings few long term side effects. Still, some patients do have long-term autoimmune side effects like thyroid problems or diabetes.

Emotional Support Before, During and After Treatment

Each cancer patient feels a huge range of emotions from fear to joy. It's vital to tell your healthcare provider how you feel. Ask any and all questions and talk about your concerns. Often, there are support systems to help you through tough times. There are experienced people who can offer answers and support.

The Bladder Cancer Advocacy Network has a helpful site with support groups and information.

Sexuality and Incontinence After BCG

Your healthcare provider can work with you directly, but in general:

  • Do not have sex for 48 hours after BCG treatment. You will have BCG bacteria in your urine after treatment. It's best to avoid sex for a few days to avoid exposure. 
  • After BCG treatment, you can have sex but some side effects may lower your interest. The small tube used with BCG can cause irritation. These symptoms should go away after a day or two.
  • Use condoms. A condom during sex for up to six weeks after treatment will protect you and your partner from the bacteria. You can ask if this is helpful for you.
  • Try to avoid pregnancy. If you can become pregnant, use birth control during treatment to prevent pregnancy.

If you've had bladder surgery, it's likely to change your sex life. It helps to talk about your feelings and things you can do. You can find other ways to be intimate with your partner after treatment. You (and your partner) may benefit from the advice of a counselor who specializes in sexual issues.

Your healthcare provider can refer you to professionals who offer sexual counseling after cancer. You can also find a certified therapist near you on the website of the American Association of Sexuality Educators, Counselors and Therapists.

Prevention of Recurrence

Although there is no guarantee that your cancer won't recur, there are certain lifestyle changes that are known to be helpful.

Things that can improve your quality of life are:

  • No smoking
  • Drinking lots of water
  • Eating a healthy diet with fewer processed foods
  • Exercising daily
  • Trying to reduce stress

Going through cancer treatment and the fear of recurrence can be very stressful. Your healthcare provider may recommend a cancer support group or individual counseling to help you manage your stress and anxiety.

What is the Plan If Cancer Continues to Recur or Grow?

Remember that each person is unique and each body responds differently to therapy. It is important to take good care of yourself and remain in contact with your healthcare provider. For very aggressive cancers, clinical trials are often recommended as they may offer additional hope.

Clinical trials are research studies that involve people that test new treatments or procedures to see if they are safe and effective. By taking part in in a clinical trial, you may help yourself, and you can help move science forward.