Transcript of Using Immunotherapy to Treat Bladder Cancer with Dr. Brendan Guercio

January 16, 2024

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Voice over:

This is Bladder Cancer Matters, the podcast for bladder cancer patients, caregivers, advocates, and medical and research professionals. It’s brought to you by the Bladder Cancer Advocacy Network, otherwise known as BCAN. BCAN works to increase public awareness about bladder cancer, advances bladder cancer research, and provides educational and support services for bladder cancer patients and their loved ones. To learn more, please visit bcan.org.

Rick Bangs:

Hi, I’m Rick Bangs, the host of Bladder Cancer Matters, a podcast for, by and about the bladder cancer community. I’m also a survivor of muscle invasive bladder cancer, the proud owner of a 2006 model year neobladder and a patient advocate supporting cancer research at the Bladder Cancer Advocacy Network, or as many call it, BCAN, produces this podcast. I’m pleased to welcome today’s guest, Dr. Brendan Guercio. Dr. Guercio is a medical oncologist and an assistant professor at the University of Rochester Medical Center in Rochester, New York. Dr. Guercio completed a medical oncology fellowship at Memorial Sloan Kettering Cancer Center and received his MD from Harvard.

His areas of expertise include the use of cutting edge immunotherapy, chemotherapy, and hormone therapy in the treatment of genital urinary cancers with a focus on the development of new forms of therapy through clinical trials. Dr. Guercio received a young investigator award from the ASCO Conquer Cancer Foundation, and has been a recipient of research support from the NIH, the National Institutes of Health, and the National Cancer Institute, the NCI. He’s also the recipient of the 2021 BCAN Young Investigator Award for his research focused on the impact of diet on immune checkpoint inhibitor, therapeutic response and tolerability in bladder cancer patients. Dr. Guercio, thanks for joining our podcast today.

Dr. Brendan Guercio:

Thank you very much for having me. I’m a big fan and it’s a real honor to be here.

Rick Bangs:

We are fans of yours as well, so looking forward to this. So I want to talk about your Young Investigator Award, your BCAN Young Investigator Award because it was in an emerging and very fascinating space. And so I want to set the stage for our listeners first and talk about immunotherapy, which as you know, in a few short years, has really revolutionized treatment for bladder cancer. And most of our listeners would know that BCG is the most famous of the immunotherapies in bladder cancer, though recently, others have come on the scene and delivered some fantastic results for our patients. So how does immunotherapy work and how is it different from chemotherapy?

Dr. Brendan Guercio:

Immunotherapy is a really interesting type of therapy because it works by training our immune systems to identify and fight cancer cells for us, which is very different from chemotherapy, which traditionally works by directly killing the cancer cells, usually by causing DNA damage in the cancer cells. Immunotherapy also has very different side effects from chemotherapy, and in many cases can be more easily tolerated than chemotherapy.

Rick Bangs:

And so your work focused on a specific type of immunotherapy called the immune checkpoint inhibitors, so what are they and how do they work?

Dr. Brendan Guercio:

Immune checkpoint inhibitors are an intravenous type of immunotherapy that’s used in many different types of cancers now. They work by blocking special proteins called immune checkpoints that cancer cells use to turn the immune system off. And by blocking those immune checkpoints, the immune checkpoint inhibitors basically allow the immune system to reactivate and fight the cancer the way it’s supposed to do normally.

Rick Bangs:

Wow. So it’s what we would like to think would happen naturally, but doesn’t always because of the way cancer works. So how effective are checkpoint inhibitors as a treatment option?

Dr. Brendan Guercio:

It can vary a lot depending on which specific type of cancer you’re talking about and even the specific type of cancer for an individual person. But in general, for patients who have advanced bladder cancer, about a quarter to 30% of them will have significant shrinkage of their tumor in response to checkpoint inhibitors. And for the patients that are fortunate enough to experience a significant amount of shrinkage, those responses can actually last a long time, often on the order of a few years or more.

Rick Bangs:

So 20, 25% is a decent amount. We’d like it to be more but it’s still pretty decent compared to where we’ve been historically. So as a patient, what things that impact the immune response do I control?

Dr. Brendan Guercio:

I think the most important thing to making sure that the immunotherapy works well is making sure that folks work with their personal physician very closely to ensure that the treatment goes smoothly, and so that any side effects from the treatment are caught early so that they can be managed well. Right now, we unfortunately don’t know much else for sure. There is some exciting early data suggesting that some specific probiotics might help. And our own study, which we’ll talk about, which was funded by BCAN, suggested that higher intake of dietary fiber might help. But we do need larger and higher quality studies in the future to confirm those early findings. But in general, we do know that immunotherapy can really only work if your immune system is working too. And since the immune system is a normal part of every person’s body, it seems plausible that trying to live a healthy lifestyle with healthy habits might help the whole body remain healthier and help the immune system work better too.

Rick Bangs:

Yeah, that makes complete sense. So how do we connect the dots between immunotherapy, what we eat and what’s called gut health?

Dr. Brendan Guercio:

Great question. So there’s many, many bacteria that live in our gut. There’s actually more bacterial cells that live in our bodies than human cells. And multiple studies in recent years have suggested that bacteria that live in our gut actually interact with and have effects on our immune system and ultimately impact how well immunotherapy works. And since the bacteria in our gut eat whatever we eat, changes in the diet can actually have big effects on the gut microbiome, which is the population of bacteria that live there. So my research team and others have started to try to study how diets can be changed to hopefully help the gut microbiome make immunotherapy work even better.

Rick Bangs:

That would be really cool. So let’s talk about some specific items that we eat that might have an impact on immunotherapies and gut health. So first up is something we would call probiotics. So what are probiotics and how might they, in theory, and maybe even in practice, relate to immunotherapy?

Dr. Brendan Guercio:

Probiotics are live bacteria that we can ingest in order to try to modify our gut microbiome, usually by adding good bacteria or bacteria that we think will help other good bacteria work better. And they can come in a lot of different forms. Sometimes probiotics come in pills and supplements. Other times, they might come in the form of live bacterial cultures that are in certain foods, like yogurts or certain fermented foods. And it’s very important to understand that not all probiotics are the same. So while some research suggests that some probiotics might be helpful, it’s also possible that others might be harmful. So it’s best for patients to discuss probiotics with their physician before trying them themselves.

And while several studies have suggested that certain probiotics might be beneficial, the most promising one so far is called CBM 588, which is also called clostridium butyricum. And that’s a probiotic that’s actually been used in Japan for a long time to treat digestive issues that’s caused by antibiotics. And so far, the CBM 588 probiotic looked like it made immunotherapy work better in two small randomized trials of patients with advanced kidney cancer. But because those trials were small, we’re still waiting for larger trials to hopefully confirm that those findings are accurate.

Rick Bangs:

So anybody who’s taken a probiotic would remember that there’s a list and it’s different. You pick up one versus another. It’s different. You’ll have to tell me if I’m wrong, the one that you just mentioned, if I were to go to my local store and try to buy a probiotic, would I be able to even find this one as one of the probiotics? Or is this something that is fairly restricted in its use today?

Dr. Brendan Guercio:

Yeah, it’s a great question. In the US, it is actually somewhat restricted in availability. And even though there are places that you can try to buy it online, not all CBM 588 formulations are the same. So the ones that you do buy online are not necessarily the same one that was used in the trial. So the devil’s really in the details there, and we don’t know if they would work the same way.

Rick Bangs:

So we need more studies and then if it did work, we’d want it to be… the quality to be consistent and some guidance on how to take it, when and take it, how much, so forth. All right, so the jury’s still out, is what you’re saying?

Dr. Brendan Guercio:

Exactly.

Rick Bangs:

What about prebiotics? What are they? And in theory and in practice, how might they relate to immunotherapy?

Dr. Brendan Guercio:

So prebiotics are another way to potentially modify the gut microbiome to hopefully make it work better. They work by basically acting as substances that good bacteria ferment in the gut, and basically, promotes the function and abundance of those good bacteria. And some well-known prebiotic examples are resistant starch, inulin, fructooligosaccharide. And by feeding the good bacteria, there’s a chance that, theoretically, they might help immune checkpoint inhibitors work better. There have been studies suggesting that prebiotics help the immune system work better in animals. There have not really been studies like that in people with bladder cancer yet, but there are now some studies starting to look at prebiotics in patients with cancer receiving immunotherapy in general. For example, there’s a trial at the University of Michigan that’s looking at whether a prebiotic potato starch might be safe and helpful for patients in that context.

Rick Bangs:

I wouldn’t even think about potato starch as being a prebiotic. That’s interesting. So what about fiber, how might fiber, in theory and in practice, relate to immunotherapy and to prebiotics and probiotics?

Dr. Brendan Guercio:

When we eat fiber, fiber is actually also fermented by bacteria in our guts. And in fact, some types of fiber, including inulin and fructooligosaccharide, are considered to be prebiotics. So the bacteria that feed on fiber are usually thought to be good bacteria, and eating fiber might basically feed the gut microbiome what it needs to function better and hopefully help the immune system work better when it’s being treated with immunotherapy.

Rick Bangs:

So can you consume the right versions and the right quantities of prebiotics and probiotics and fiber without using supplements? Can I get enough of these and can I get the right ones? And if so, how would that happen?

Dr. Brendan Guercio:

Maybe. But the truth is that we don’t really know yet what the exact right versions and quantities are. So there are these early signals that more dietary fiber and certain probiotics might be helpful, but there hasn’t been enough research to necessarily say exactly how much of those is needed and what version is needed. In our own pilot study that was funded by BCAN, we found that patients with bladder cancer receiving immunotherapy seem to do better if they had at least 17 and a half grams of fiber per day in their diet. That actually is similar to a study that was done in melanoma at MD Anderson where they found that at least 20 grams of fiber per day was associated with better outcomes. And that amount of fiber is not actually very high. In fact, that much fiber can be contained in a single cup of some high fiber cereals. But we’re planning more studies to help clarify the optimal amount of fiber since our initial study was small and preliminary.

Rick Bangs:

And so what do we know about the average American, how many grams of fiber would an average American get, do you know?

Dr. Brendan Guercio:

Sadly, probably not enough. That’s 17-

Rick Bangs:

Yeah, that’s what I guess.

Dr. Brendan Guercio:

… and a half. Yeah. Unfortunately, western diets are very low in fiber and almost never meet the recommended amounts of fiber that we should have in our diet.

Rick Bangs:

So even though 20 grams is associated with better outcomes and theoretically, not a lot, the average American probably not getting that. So are supplements better or worse or the same as dietary intervention in this context?

Dr. Brendan Guercio:

It’s a really great question that really needs more study. While we have some hints that dietary fiber might help, it really hasn’t been studied yet, whether it’s important for that fiber to come from supplements or whole foods. We know from some areas of medicine that nutrients from foods and supplements can work similarly. So for purposes of keeping our bones strong, physicians often recommend to patients that they consume enough calcium and vitamin D in their diet. And we know that whether that calcium or vitamin D comes from whole food, like milk or dairy products or a supplement doesn’t seem to be very important. But whether or not that’s the case for nutrients like fiber isn’t yet determined.

Rick Bangs:

So more the jury is still out. So if my source of fiber is from my diet, I’m obviously eating more fiber than the average American, and I was participating in a clinical study, how would you measure how much I’m actually getting? And then I think this would be important to you in a clinical study, ensure there’s some consistency between me and other people who are part of the clinical trial and getting sufficient dosing from day-to-day in a consistent manner.

Dr. Brendan Guercio:

That is a super important question, and there are a couple of different ways to go about it, depending on how the study is conducted and designed. One possible example is providing prepared meals to participants in the study. In that way, researchers can have a pretty accurate idea of how much fiber or other nutrients the study participants are consuming every day. That’s probably the most accurate way to do it, but it’s also relatively costly and resource intensive. There’s other ways to do it too. Researchers could simply prescribe study participants a fiber supplement to guarantee that everyone in the study is consuming at least that amount of fiber.

There are other more efficient ways like having patients keep a daily food diary where they basically just record everything they eat and keep track for the investigators, or they can even periodically complete so-called food frequency questionnaires, where study participants fill out a questionnaire where they describe how much of a variety of foods they’ve taken in over a certain period of time, like the past three months, and then researchers can use that data to estimate a person’s average daily intake of nutrients like fiber.

Rick Bangs:

So how would you ensure that someone in the control groups… so I’m in a study and I’m in the control group, how would you make sure that I’m maintaining my normal diet and not tipping the scales and adding some fiber?

Dr. Brendan Guercio:

That’s really tricky. Some of the approaches I mentioned could be used in some studies. There will even be placebo controls where the people in the study don’t know if they’re receiving, for example, a fiber supplement or a placebo supplement. That might be fiber, might not, but at the end of the day, obviously, researchers can never really restrict study participants from eating what they want. So researchers are always relying a little bit on the goodwill of study participants to follow the rules of any study to hopefully ensure that the studies findings are valid and helpful to future patients.

Rick Bangs:

What about antibiotics? Many bladder cancer patients are prescribed antibiotics, either prior to surgery or because of a UTI or perceived UTI. So how might antibiotics relate to immunotherapy?

Dr. Brendan Guercio:

Antibiotics are interesting because there’s a number of studies now that have suggested that antibiotics might be harmful to the gut microbiome and cause immunotherapy to perform less well. That said, it is really important for people to receive antibiotics if they have a real bacterial infection because untreated bacterial infections can lead to hospitalizations and even death if they’re really going untreated for a long time. Urinary tract infections, for example, which happen often in folks that are affected by bladder cancer often do require antibiotics, even if there is a chance it might cause immunotherapy to work a little bit less well.

But that said, there are some situations where antibiotics are often used but not really needed. So a lot of folks might choose to take antibiotics for the common cold, just in case it might help, even though the vast majority of the time, the common cold’s just a virus and not a bacteria. So the antibiotic can’t really help. So I think the data is strong enough to at least suggest that if you have a situation where your physician tells you that an antibiotic isn’t really necessary, then maybe that’s a good thing and just skip on the antibiotic.

Rick Bangs:

I think that’s great advice. So I want to connect the dots to bladder cancer treatments. So what do we know about probiotics, prebiotics, fiber and antibiotics and their impact on immunotherapy in terms of response to treatment and perhaps even tolerability? What have some historical studies told us?

Dr. Brendan Guercio:

So overall, I think there are promising signs that these tools might help us make immunotherapy work better soon. The data’s still a little early, so prescribing probiotics and supplements to patients receiving immunotherapy is not standard yet, but there is likely enough data to suggest that avoiding antibiotics when they’re unnecessary, like the common cold is probably a good idea, eating a generally healthier diet, which usually is high in fiber by default, probably doesn’t hurt, and it may be helpful. Larger studies are hopefully going to be done soon to confirm and clarify the roles of these potential tools and improving outcomes for patients and people affected by bladder cancer. But one thing that I think is nice is that if eating a healthy diet is what’s helpful, we know that eating a healthy diet is good for a lot of reasons, like beneficial effects on the heart, blood pressure, blood sugar levels. So it certainly probably doesn’t hurt folks to try to eat a healthy diet while more details about this topic are being worked out by researchers.

Rick Bangs:

That’s an important help. It’s an important point. It’s certainly not going to hurt, so. All right, any similar findings regarding chemotherapy, not immunotherapy, but chemotherapy?

Dr. Brendan Guercio:

Yeah. Unfortunately, there’s not been very much research into the effects of nutrition in the microbiome and chemotherapy and bladder cancer, specifically. There has been in some other diseases, so for example, in colon cancer, there have been studies that suggest that healthier diets and lifestyle and exercise might help reduce the chance of colon cancer coming back after patients have had surgery and chemotherapy to treat the colon cancer. But whether those same associations exist in bladder cancer remains to be seen. I think it’s an important area that we should study. Although, since chemotherapy may soon start to take a backseat to newer and more effective medications in the future, it’s possible the importance of that question may actually diminish over time.

Rick Bangs:

Which is not necessarily a bad thing. So I want you to look into your crystal ball, and what kind of work do you foresee in the future?

Dr. Brendan Guercio:

Well, a lot of the studies that have been done to date have been what we call observational studies, meaning that we invite folks to participate in the studies, ask about their diets or their probiotic use, and then see how they do, which are a very efficient and important early type of research. But the next step is really randomized trials to prove that what we found in those early studies is the real deal. And so I’m really hopeful that we’ll see many more randomized trials in the future, investigating all the possibilities that we discussed today, hopefully, even in combination with one another, because one could imagine that combining probiotics with specific types of diets or prebiotics might be more helpful than any one strategy alone.

Rick Bangs:

We definitely need more data. So I want to pick your brain. What advice would you have for a newly diagnosed patient receiving or about to receive treatment relative to this topic?

Dr. Brendan Guercio:

So I would definitely recommend that first and foremost, they discuss the topic with their own personal physician because every person’s situation is unique and should be tailored to them. And I would note that a lot of the data we’ve talked about today is very exciting, although we do need more studies to confirm that these signals are real. I think it’s also important to remember that all the studies so far suggest that these strategies might help cancer treatments work better, but they’re not substitutes for the cancer treatments that we use in of themselves. And the good news is that in general, this study suggests that doing things that we generally think would be healthy, like eating a fiber rich diet, might be good for us. So they can continue to do that for all the reasons that are already well established reasons for doing it, like heart health and blood sugar control.

Rick Bangs:

Any final thoughts?

Dr. Brendan Guercio:

I’ll just emphasize how important I think organizations like BCAN are to furthering research in this area and how much I appreciate BCAN for supporting this kind of research in the past because studies of diet are really important, but some traditional research funding sources aren’t as likely to support it. And that makes organizations like BCAN, which are very focused on the needs and desires of patients, a really indispensable resource in this field.

Rick Bangs:

Amen to that. So Dr. Guercio, I want to thank you for giving us an understanding of the relationship between immunotherapy, and immune checkpoint inhibitors, and prebiotics, probiotics, fiber, and antibiotics. If you’d like more information on bladder cancer, please visit the BCAN website, www.bcan.org. In case people wanted to get in touch with you, would you be willing to share a Twitter handle or other information that you would like people to have?

Dr. Brendan Guercio:

Absolutely. My Twitter handle is @BrendanGuercio. No spaces or punctuation. And that’s spelled B-R-E-N-D-A-N G-U-E-R-C-I-O.

Rick Bangs:

Excellent. Just a reminder, if you’d like more information about bladder cancer, you can contact the Bladder Cancer Advocacy Network at 1888-901-2226. That’s all the time we have today. Be sure to like, comment, and subscribe to this podcast so we have your feedback. Thank you for listening, and we’ll be back soon with another interesting episode of Bladder Cancer Matters. Thanks again, Dr. Guercio.

Dr. Brendan Guercio:

Thank you.

Voice over:

Thank you for listening to Bladder Cancer Matters, a podcast by the Bladder Cancer Advocacy Network or BCAN. BCAN works to increase public awareness about bladder cancer, advanced bladder cancer research, and provide educational and support services for bladder cancer patients. For more information about this podcast and additional information about bladder cancer, please visit bcan.org.