A Deeper Look Into a 40-Year-Old Bladder Cancer Treatment: Bacillus Calmette-Guerin

While immunotherapy seems to only be a recent trend in the treatment landscape for a variety of cancers, one type was actually used to treat superficial bladder cancer more than 40 years ago — and it is still used in some non-invasive bladder cancers today.

Bacillus Calmette-Guérin (BCG) therapy is a type of immunotherapy used to treat patients with high-risk non-muscle-invasive bladder cancer after transurethral resection.

CURE spoke with Matthew Mossanen, M.D., from the Division of Urology at Brigham and Women’s Hospital, about what BCG is and what patients should know about this treatment option.

In simple terms, can you explain what BCG is and how it works in bladder cancer?

BCG is a type of immunotherapy for bladder cancer. It really started getting used for bladder cancer in the 1970s or so, and it was used in other cancers earlier than that. So, what we have done in urology is basically take a strain of bacteria and weakened it to use for bladder cancer.

The mechanism, or the way it works, is that you create a liquid with the medicine, and put it inside the bladder. And when it is in the bladder, it actually activates the patient’s immune system, turning on the immune cells — the T cells specifically – and it attacks the abnormal cells in the bladder that are cancerous. In that regard, it is a really clever design because you can put BCG in to the bladder and it activates the immune system, but the bladder itself serves as the perfect barrier to prevent it from getting in to the body. It is a really great treatment for patients with non-muscle invasive bladder cancer.

In bladder cancer, which group of patients should be treated with BCG?

BCG is a good option for patients with non-muscle invasive bladder cancer. The diagnoses that we can think about when we want to use BCG are carcinoma in situ (CIS), high-grade disease or patients with T1 disease, and in cases of patients who have disease that is categorized as intermediate- or high-risk disease.

It is one of the most well studied treatments. In each case, every patient and diagnosis are unique. So, it is very important to talk to your urologist about it if you do have high-risk non-muscle invasive bladder cancer.

Are there any notable side effects from BCG patients should be aware of? If so, what should patients be on the lookout for?

Because it is a medicine that is going in to the bladder, it can impact the bladder. So, patients may have symptoms while they are on therapy. The key is to communicate with your doctor, so you can work together to manage them.

Some things that can happen are cystitis, which is like a bladder infection; a urinary tract infection; dysuria, which is kind of like burning; hematuria, which is blood in urine; and some patients just kind of feel a little tired or have some low-grade fevers. Usually we can manage these side effects with medications, and hopefully they get better in a day or so.

In certain situations, there are more serious side effects, and those are some of the things we worry about sometimes. One sign to really watch out for is a fever greater than 101. We also worry sometimes that BCG can maybe get in to the blood stream, and that can cause a serious infection. And if that is the case, usually you should either call your doctor or go to the emergency room right away because you might need blood tests to check your blood for an infection followed by strong, broad-spectrum antibiotics that help control the situation.

How does BCG compare with other bladder cancer treatments? Are there any limitations?

It’s a great therapy for the majority of patients that get it. So, the good news is that many patients will have an initial response that is favorable. The cancer will respond. But there are some limitations in that, while BCG can reduce the cancer recurrence rate, which is cancer coming back, or progression, which is cancer getting worse, it is not perfect. So, one of the limitations of that is that some people, we say “fail” BCG therapy, which just means the cancer continues to come back or continues to grow. And we worry about that because then it can spread, and that can be dangerous. So, one of the limitations is to realize that it is not a perfect treatment.

Are there any trials evaluating BCG right now?

That is a great question, and fortunately is has an exciting answer. Non-muscle invasive bladder cancer is a really complex disease. Right now, researchers are looking at using BCG in combination with other therapies in the bladder or vaccinations. Beyond BCG, researchers are also looking at studying different ways of treating these patients using things like genetic therapy, oral or IV immunotherapy, radiation and a number of other agents. There are a number of clinical trials in progress.

It is also important and exciting to know that there is a lot going in to biomarkers, or ways to predict who will have a response to these medications by looking at either a blood or urine test. So, right now is a very exciting time in bladder cancer because of a lot of active research going on in this space.

What is one key area that patients should know about with BCG?

It is important to realize that if you have non-muscle invasive bladder cancer, this can be an effective treatment. It’s not perfect, but it should definitely be discussed with your urologist. If you do get treatment, you should be followed closely afterwards. So, the takeaway point is that BCG is one step in your treatment, and after you receive it, you still need to see the urologist regularly for ongoing surveillance, which includes cystotomies.