New Test May Identify Those Unlikely to Respond to Popular Bladder Cancer Treatment

The advent of immunotherapy has been one of the most exciting advancements for the treatment of bladder cancer. However, there is still a group of patients who will not respond.

While there is currently no definitive way to predict who will respond and who will not, researchers at Brighton and Sussex Medical School in the United Kingdom are working on a blood test that could identify about half of those who may not. The test evaluates patients’ responses to Tuberculin — which is often used to test people for tuberculosis – to pick out who may not respond to BCG immunotherapy.

We spoke with Florian Kern, M.D., FRCP, author on the study and chair in immunology at the Brighton and Sussex Medical School, about the findings.

Can you explain why it was important for you to conduct this research and find that a simple blood test might identify patients with bladder cancer who won't respond to immunotherapy?

I was intrigued by the fact that the same bacteria that are used in a tuberculosis vaccine can successfully “train” our immune system to fight cancer. But it does not work in everybody. I thought that a test similar to the one used to see if a patient has been in contact with tuberculosis might provide the answer if it does or does not. It is important to develop simple and cost-effective tests if they are to be used in many patients.

Can you briefly explain your study and the findings?

We studied patients receiving immunotherapy for superficial bladder cancer. The immunotherapy, in this case, consists of injecting live bacteria into the bladder after the cancer is removed surgically. The bacteria are the same that are used in the tuberculosis vaccine. The immune system then responds to the presence of these bacteria. This kind of therapy is only provided for superficial bladder cancer, that is, cancer affecting only the cells lining the inside of the bladder.

It is a quite successful therapy, however, in around a third of patients, cancer cells grow back after a few months or a bit later. This means that the immune response was not sufficient. Our test works on the basis that, before therapy is started, immune cells taken from a blood sample are exposed to protein extracts from tuberculosis bacteria and if they are recognized, the immune cells will set free a substance referred to as Interleukin-2. We found that in patients whose immune cells do not release a lot of Interleukin-2 in this test, the immunotherapy will fail.

Is there any current way to determine if a patient will or will not respond to immunotherapy? What are the signs that they are not responding?

There are other tests around, however, the best one that I am aware of does not work until sometime into the therapy and is a lot more involved. It requires that treatment has taken place and looks at changes in a number of different parameters over time. This is more complicated and more expensive and does not provide any help regarding treatment decisions in the beginning. The ultimate sign that a patient is not responding to immunotherapy is the renewed growth of tumor cells in the bladder.

Obviously, if a person does not respond to immunotherapy they will not benefit, but are there any negative consequences?

The negative consequences are mainly related to the loss of time until a different treatment that is more suitable for these patients can be given. This may have negative consequences for their survival.

There is, of course, the disappointment of the patient, a potential loss of hope and the possible side effects the patient had to put up with. While the treatment is generally quite safe, there are some real risks. For example, the bacteria can spread in the body and cause a dangerous infection. This is rare, but imagine this happening in someone who would not even have benefitted from the procedure.

What are the next steps in this line of research? Will patients eventually have access to this blood test?

We would like to run a clinical study with a larger number of patients in order to show that our test is robust and reliable. What we have published here are the results of a smaller pilot study. It now needs to be shown that the test performs equally well in a big study. This would also give us an opportunity to fine-tune and maybe improve the test, also with a view to predicting therapy success. In the pilot study, the best performance of the test was in predicting failure before therapy had even started. If the larger study confirms the results of the pilot study, the test could be made available quite quickly, as it is technically very simple and a similar test already exists for tuberculosis.

Is there anything else you'd like to add?

I hope that we can do a clinical study in the near future in order to make this test available as soon as possible. These are exciting times with lots of immunotherapies for different types of cancer being tested worldwide. Some of them have severe side effects and are hugely expensive. It will be a great challenge, therefore to find good tests to predict the success or failure of these new therapies as early as possible.