The potential of the microbiome to enhance bladder cancer care

In this interview, Laura Bukavina, MD, MPH, highlights the recent Bladder Cancer Advocacy Network (BCAN) Think Tank that took place in Washington DC, as well as a session that she co-chaired at the meeting titled, “The oncoboime: Real world applications of microbiome in bladder cancer.” Bukavina is an assistant professor of urologic oncology at Case Western Reserve University in Cleveland, Ohio.

Laura Bukavina, MD, MPH

Could you provide an overview of the BCAN Think Tank?

I had the honor of attending my second BCAN Think Tank this year. If anyone has ever been to a think tank of any sort, and I think this one is very different than the remainder, a think tank has a common goal. A think tank is meant to collect people of the same aim, [in this case,] in terms of treating bladder cancer.

However, unlike our typical conferences, such as [the American Urological Association] or [the Society of Urologic Oncology], [where] we have people from the same settings; [namely], urologic oncologists or urologists, a think tank has individuals from all walks of life. So, not only patient advocates, patient providers, and patients themselves, we also have people outside of urology. You have radiologists, radio-oncologists, basic scientists, translational scientists, and people outside urology research­–people in immunology research and things, potentially, that could be applicable to the problem that we're facing, and that's treatment of bladder cancer.

You also co-chaired a session at the meeting on the microbiome in bladder cancer. Could you highlight a few key takeaways that came out of those discussions?

I had the honor of also co-chairing the oncobiome session. I do have to give a shoutout to Dr. Shilpa Gupta at Cleveland Clinic; she wasn't able to attend, however, she did partake in a lot of organization as well. We [also] had 3 wonderful speakers. Dr. Leigh Greathouse and Dr. Patricia L. Hibberd focused on multiple aspects of the microbiome, but more so in terms of rigorous science, as well as where we can take the research in microbiome and how we can apply this to our patients with bladder cancer. For example, Dr. Greathouse talked about nutrition and nutritional support of our patients with bladder cancer during their therapy, whether it's chemotherapy or immunotherapy, and things that we're learning in terms of microbe, microbiome, and probiotics support for those patients during treatment. Having been a cancer survivor herself, she's acutely aware of how your diet changes how you respond to treatment. Not only so, but also how you're able to handle a lot of the toxicities of treatment.

Then, the other aspect that we talked about was the microbiome as a biomarker. I spoke about some of the research that we currently have in stool and using it as a microbiome predictor for chemotherapy response. There are different ways you can think about it. I think most people when they think about the microbiome, they think of H. pylori causing gastric cancer. This is not where we're going with this. Where we're going is that we know that people respond differently to chemotherapy based on their signature of bacteria. Why is that happening? Is it an immune-mediated phenomenon? Is your immune system better able to fight off cancer and work with chemotherapy or immunotherapy? Or are the bugs themselves metabolizing the drugs? About 25% of the drugs are diluted down based on your bacterial composition. So, if you're getting chemotherapy and your microbiome is not favorable, are you really getting a lower dose of what actual chemotherapy you should be getting? That's one of the things that we talked about.

[On] the other side of the spectrum, we talked about FDA approval of probiotic therapy and microbial therapy in patients. There's been a lot of talk about the FDA's resistance to approving these drugs. If you look at a lot of the probiotics currently in stores, they're not FDA approved, because the FDA has rigorous scientific qualifications in what they can consider to be therapeutic. We talked about ways to handle this FDA resistance to a lot of the probiotics and treatment, as well as potentially applying more of the rigorous scientific approaches in doing probiotic studies in combination with our clinical trials. Once we have these data, we'll be able to present it to the FDA a lot more efficiently.

What are some current unmet needs in this space?

I think there are a lot of unmet needs in patients with metastatic disease. A lot of the studies we have been doing now are focused on localized and intravesical therapy. We currently treat with intravesical therapy – we use Bacillus Calmette-Guérin (BCG),which is a bacteria, so we consider that to be a microbiome research as well. There's a lot of need in thinking about how we can augment response by altering the urinary microbiome so that BCG has a chance to work better. The other thing we talked about is the unmet need for our patients with metastatic cancer, the ones that are getting immunotherapy, and how we can improve their response long term.

Could you highlight some of your own ongoing research on this topic?

Some of the exciting things right now as I'm transitioning to Case Western and building my lab here are talking about our urinary studies. We have discussed some of the BCAN-funded studies this year, which include instillation of Lactobacillus rhamnosus GG (LGG). LGG is a subspecies of a lactobacillus, which we all know is what we consider to be a good bug. Lactobacillus actually outperformed BCG in my studies in terms of treatment of bladder cancer. We're very hopeful that potentially we can use LGG in combination with BCG down the line. Clearly, we need more reproducible data. This only has been done in about 10 cages of mice, but we’re currently working on more of the same experiments to make sure we get similar data.

[At the meeting,] we talked a lot with our veterinarians. Veterinarians are a big part of the BCAN think tank, [because] bladder cancer is prevalent in dogs, and they actually have a very similar histology and staging to humans. So, they might be a better model for bladder cancer than mice. If we're getting really great results with our LGG, the reasonable next step is to potentially trial this therapy in dogs with bladder cancer.

How do data on the role of the microbiome shape clinical care for patients with bladder cancer?

It's difficult at this time to recommend it, because a lot of it is on the basic science translational side of things, and it's not FDA approved. We did have a lot of discussion currently with our post-cystectomy patients, and a lot of them are getting infections in terms of what probiotics they should be taking. It's difficult to recommend anything. I think it's too early to recommend anything with 100% certainty. I would say hold off for the next couple of years. I think we're going to have really good data about what we should be recommending not only to prevent infections, but potentially improve the efficacy of treatment.

Is there anything else that you’d like to add?

I would encourage anyone who is treating patients with bladder cancer and any bladder cancer patient out there reading this to come to BCAN Think Tank or become involved with BCAN. It's a great organization. It has amazing patient advocates. Patients play a huge part in how we think about bladder cancer and how we address it. I would highly recommend anyone who's doing any bladder cancer research to be part of this.