Ask the Experts 2024 Transcript

May 28, 2024

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Rebecca Johnson:

Welcome to the Ask the Experts live event. I am Rebecca Johnson, vice president of Research, Education and Marketing for BCAN, the Bladder Cancer Advocacy Network. I’m honored to be hosting this evening’s event, which is one of my favorite BCAN programs. Today, we’ll be joined by two guest experts who will discuss what we currently know about bladder cancer treatment and advancements and answer questions submitted by you, tonight’s viewers.

We received over a hundred questions from participants and we’ll do our best to capture many of the themes and the questions raised. But I apologize in advance if we don’t get to your particular question due to time constraints. Please keep in mind that this program is not meant to answer case-specific questions, and we always recommend discussing those questions with your doctors.

We hope that you’ll remain with us until the end of the program when I’ll announce the 2024 BCAN of Hope Award recipient. BCAN was founded in 2005 by Diane Zipursky Quale and her late husband, John Quale after they discovered just how little information was available for bladder cancer patients and about bladder cancer treatments. And were shocked by the fact that the way bladder cancer was treated had not changed in three decades.

They founded BCAN to be an organization focused on improving the lives of bladder cancer patients and loved ones, providing trustworthy information for patients, and bringing attention to bladder cancer and the need for increased funding for bladder cancer research. I think I can say on behalf of Diane that this is exactly what BCAN is doing today as we approach our 20th anniversary next year.

Advancing bladder cancer research has been a critical part of BCAN’s mission from the start and remains so today. As evidenced by the multiple and growing research award programs. BCAN’s research award programs focus on funding innovative science, filling in the gaps, and funding the best and brightest researchers. One of the ways that we do this is through our Young Investigator Award program that supports early career researchers and clinicians who want to dedicate their expertise and talent to a career in bladder cancer. To date, BCAN has made 37 Young Investigator Awards.

Today’s program not only provides an opportunity to have your questions answered by bladder cancer experts, but also offers BCAN the opportunity to showcase our young investigator program. As both of the experts joining us today, were past recipients of this award. BCAN’s research program exists due to the generosity of others, including David Pulver, a member of BCAN’s Board of Directors, and someone who has been integral to our Ask the Experts program for years. While we have accomplished much, there is still so much more to do to create more and better tomorrows for patients and those who love them.

If you would like to support BCAN’s Bladder Cancer Research program, I encourage you to visit bcan.org/researchfund to make a gift. Your contribution will drive innovative research to improve our understanding of bladder cancer, find new and novel approaches to diagnosing and treating bladder cancer, and to improving patient outcomes. Thank you so much in advance for your generosity.

I now am excited to introduce our first expert joining us this evening, Dr. Matthew Mossanen who received a BCAN Patient-Centered Clinical Research Young Investigator Award in 2020. Dr. Mossanen is a urologist at Brigham and Women’s Hospital in Massachusetts and an assistant professor of surgery at Harvard Medical School. Welcome Dr. Mossanen, and thank you so much for joining us.

Dr. Matthew Mossanen:

Thank you very much for having me.

Rebecca Johnson:

I would also like to welcome Dr. Brendan Guercio, recipient of a Young Investigator Award in 2021. Dr. Guercio is a medical oncologist at the University of Rochester Medical Center. Thank you so much for being here, Brendan.

Dr. Brendan Guercio:

Thank you. Thank you very much for having us.

Rebecca Johnson:

Both of tonight’s experts are actively engaged in the BCAN community in many ways and we’re grateful to have them here today.

And lastly, before we get started, I do want to share that there is no need to take notes tonight. This video is being recorded and will be posted on the BCAN website, bcan.org, in just a couple of days. So let’s get started with a couple of questions. I’ll stop talking so much and turn it over to you both.

I’d like to start off with a question for both of you to respond to. We can start with Matt, and that is that you’re both very actively involved in bladder cancer research. I would love for you to just briefly share in two minutes or so, the nature of your research and its potential impacts for patient treatment outcomes and on patient’s lives.

Dr. Matthew Mossanen:

First off, Rebecca, Stephanie, the whole BCAN crew, thank you for inviting me. This is a really big honor to be able to speak to so many people at once and to be entrusted with answering the questions for so many patients. I really appreciate the invite.

The brief summary is I’ve been involved in bladder cancer research since I was a resident. I had a dedicated research year. I applied for a travel fellowship. And as an attending, I was fortunate enough to receive the Young Investigator Award. My research, there’s a couple of different areas that I’m focused in. My BCAN award was for exploring ways to help bladder cancer patients quit smoking. I’m also working on a number of clinical trials and trying to get those off the ground, and also the use of interesting technology to improve the way we do surgery and the way we take care of patients. Thanks again for inviting me to be here.

Rebecca Johnson:

Thank you so much. And we’ll touch on some of those items a little bit later this evening. So Brendan, could you please also share a little bit about your research?

Dr. Brendan Guercio:

Yeah, absolutely. Thank you. And I absolutely second everything that Matt said. Very appreciate the opportunity to participate in this great event. I, like him, am involved in multiple areas of research in bladder cancer. Some of those areas involve looking at things like circulating tumor DNA and bladder cancer genetics to hopefully try to tailor our treatments for patients with bladder cancer better and to make them more effective. I also work in clinical trials trying to develop new medications with the National Cancer Institute and industry partners to try and develop new and innovative treatments for patients.

And I think the most interesting area that I do work in is actually an area that BCAN helped start, which is looking at aspects of diet and nutrition in relation to outcomes for patients with bladder cancer, especially on immunotherapy because there’s been a lot of interesting research in multiple cancers in recent years suggesting that the bacteria that live in our gut may be important to how well immunotherapy works for some folks. And obviously, the bacteria in our gut eat what we eat, and so BCAN has been very generous in helping me to start a research program to look at whether or not diet might actually be able to help patients do better on those sorts of treatment.

Rebecca Johnson:

Great. Thank you. And very fittingly, we did receive questions related to that as well. So hopefully, we’ll have time to get to that this evening also. So moving into the questions submitted by our viewers. I’d like to start a little bit with questions related to screening surveillance of bladder cancer and just a little bit about who we’re seeing bladder cancer in, and why. So, Matt, I’ll start with you. Can you share the latest information on any type of urine or blood test that screens for bladder cancer? And before you respond, I’ll say I’m directing questions towards one of you, but both, please feel free to time in or provide a response.

Dr. Matthew Mossanen:

It’s a great question. So to my knowledge, the best way we screen for bladder cancer is if patients have hematuria and risk factors for bladder cancer. That can include smoking or occupational exposures to chemicals, dyes, paints, fuel, solvents. So I don’t know that we just look for it in patients, but when patients present with blood in the urine, which is one of the most common presentations, we do the workup, which includes cystoscopy and imaging.

The second part of the question, surveillance is a really big and important question. And for patients, I’ll just say with noninvasive cancer, cystoscopy is an important part of that ongoing follow-up. I will say that in the future, I think a lot of people are working on using AI to study urine and try to detect evidence of cancer and using a number of other tests that are currently under investigation to try to better detect evidence of bladder cancer in the urine.

Rebecca Johnson:

And Matt, how far away would you say do you think we are from a test like that being usable in clinics or patients?

Dr. Matthew Mossanen:

Great question. I would say, far. That would be my guess. I don’t know of anything on the close horizon, but I do know there are multiple angles people are taking. And one of the interesting approaches is to study the urine of patients on surveillance cystoscopy, for example.

And so one project that I’m involved in, takes the urine of patients undergoing cystoscopy and places it through an algorithm, and then sees how well it can predict the grade. But theoretically, you could then take that for screening. This is all sort of hypothetical and hypothesis-generating, but there are several other projects trying to parse out how we can make this test useful.

The thing that makes it so challenging is we balance these things called specificity and sensitivity, and that means, the test is really good at catching it but not being wrong when it… And accidentally telling you something is there, which it isn’t. So I don’t think there’s anything that I’m aware of yet, but lots of exciting work in progress.

Rebecca Johnson:

Absolutely. Thank you. And Brendan, to talk a little bit about who we’re seeing being diagnosed with bladder cancer. We received a question asking what is causing earlier onset or do we know what’s causing earlier onset and diagnosis of bladder cancer and other cancers in younger populations?

Dr. Brendan Guercio:

Yeah. It’s a really good and important question. And it’s interesting because there are some risk factors like those that were just mentioned like smoking that actually are decreasing overall, which runs kind of counter to what we were saying. But in general, there has been an uptick in the increase of cancers in younger adults, actually most well-documented in some other cancers like colon cancer. And there are some interesting ideas about why that might be, but the exact reasons are pretty hard to nail down because while we think it’s something probably environmental, there’s so many things that have changed in terms of people’s lifestyles and exposures in the past 50 years that it’s hard to know which one thing is the most important.

But certainly, with some cancers it does seem like more sedentary lifestyle, being overweight, eating more processed foods might be risk factors. That’s more closely tied to cancers like colon cancer and breast cancer but might be important in other cancers too. And there might even be environmental exposures that we have in greater abundance in our environment now than we did before that might play a role. Things like PFAS, which are sometimes referred to as the forever chemicals that are generated through a lot of industrial sorts of activities, and maybe microplastics or other food additives that may have effects that we’re not really aware of yet. So I think a lot of important research needs to go into that area so that we can hopefully mitigate those factors. But at a minimum, it is possible that maybe having a healthy diet and lifestyle that we know would be good for your heart and other aspects of your health anyways might help reduce the risk of some cancers. But we don’t have very good answers yet.

Rebecca Johnson:

Thank you. And relatedly, is there any new information on whether bladder cancer is inheritable or passed down? Either of you can take that question.

Dr. Brendan Guercio:

Yeah. So certainly Lynch syndrome is a really well-known type of hereditary cancer condition that more often predisposes to certain cancers like colon cancer, but can actually increase the risk of some urothelial cancers, especially varying cancers of the ureters and the inside of the kidneys, but has been observed rarely in maybe around 3% of bladder cancers as well. And there have been some other studies recently. There was one study out of Sloan Kettering that looked for inherited mutations among patients with higher-grade superficial bladder cancers that did show that there might be other mutations that are common in patients. Maybe up to 10% of patients in that study had inherited mutations in other genes that are involved in repairing DNA. And so I think one of the hypotheses generated by that study is that defects in genes that are used to keep our DNA healthy might predispose to bladder cancer. But screening for this certainly is not yet a standard thing for patients with bladder cancer and probably requires more research before it’s known exactly how impactful they are.

Rebecca Johnson:

Matthew, do you want to-

Dr. Matthew Mossanen:

The other comment that I’ll make, and that was a really nice answer, covering what is a very complicated topic. But when patients will ask, “How did this happen? No one in my family has bladder cancer and I don’t smoke.” What I’ll often ask is, “Did anyone in your family smoke?” And it’s sort of unrelated but related in the sense that while you share genes and DNA with your family, you also share the home. And so secondhand smoke is one of the risk factors for bladder cancer and I sort of treat it almost as not something inherited but something shared with the family. And so it’s something certainly to keep in mind along that theme.

Rebecca Johnson:

Absolutely. Thank you both and this conversation lends itself well to another question we received that’s sort of related. You touched on it a little Brendan talking about different genes. We are hearing a lot about genomic profiling and even blood circulating DNA, and we did receive a question that given the power of some of these tests and tumor profiling, genomic profiling, and treatment decisions, why are they not used more often? Why is that not standard for every patient? And I’ll take it to either of you that want to take this one. I’m sure you both have perspectives.

Dr. Brendan Guercio:

Yeah. Oh, go ahead.

Dr. Matthew Mossanen:

Go ahead, Brendan. Why don’t you start? Go ahead.

Dr. Brendan Guercio:

Yeah. I just wanted to say that I agree. Those are becoming increasingly important and very exciting aspects of research and are used in standard practice for bladder cancer in certain areas. For example, we definitely use genetic testing to see if patients with metastatic Stage 4 bladder cancer might benefit from targeted therapy called erdafitinib, which, the brand name is Balversa. It’s an FDA-approved pill that does help patients with that where specific types of mutations live longer, which is really great. But I think the truth is that even though we’re learning a lot more about genetics and what the DNA means in the bloodstream of our patients, we’re still waiting for the results of larger, more rigorous randomized clinical trials in most contexts to really help us know how to use those tools.

For example, there’s a lot of genes that we know are mutated in bladder cancer all the time, but we don’t necessarily have good treatments to target them yet. So that’s a very active area of research that probably will become a more important thing in the treatment landscape in the coming decades. And there’s a lot of great clinical trials going on right now looking at how to best use circulating tumor DNA, either to identify features that we can target with treatments or just to measure response to treatments and detect very small amounts of cancer in the body that we might not be able to see with standard scans or cystoscopies.

And I think, all of those are going to become very important in coming years as these trials result. But it’s important that we don’t overinterpret the data from the very early studies because although the signals are promising, sometimes they can be misleading. So we just have to make sure that we have the best data before we start using it to really make treatment decisions for our patients.

Dr. Matthew Mossanen:

Really a nice answer. And just to add to it a bit, the way I’ll typically explain it to patients is we have these powerful tools to classify bladder cancer in more detail. The question is, if you get that additional detail, will it change what treatments you have to offer? And again, echoing what has been said, but that’s the challenge. So you might be able to gain more information, but you’re still in the same place because we only have a limited number of things to offer patients in terms of medical oncology, systemic therapies, or surgery. There’s only a limited panel of things we can provide.

It will be more exciting to have long-term data in a randomized control trial where they really rigorously test these things and see how it can help clinicians make practical decisions for patients. But it is, I think, a step in the right direction. I will say that some other cancers, for example, breast cancer are subtyped based on some of the features. And as a urologist, I know very little. But I do know that, for example, the guidelines for breast cancer have some of those details integrated into the treatment paradigm, and I imagine eventually that that will hopefully be the case for bladder cancer beyond just the metastatic setting, which was just mentioned.

Rebecca Johnson:

Absolutely. Moving more towards personalized medicine truly, I think is the goal. I thought that was a really important question. So thank you both for addressing that. I do want to spend just a minute or two talking about recurrence, and we did receive a number of questions about that. And we know that bladder cancer can have a high rate of recurrence and requires surveillance. So Brendan, can you comment on the likelihood of recurrence following treatment for low-grade bladder cancer?

Dr. Brendan Guercio:

Yeah. Low-grade bladder cancer is interesting because it very often does not progress or spread in the body the way the higher-grade bladder cancers do, which is certainly a good thing. But it can frequently come back certainly more than 50% of the time, even after it’s scraped out of the bladder by a great urologist like Dr. Mossanen with us tonight. I think the nice thing is that, even if it comes back, it can still be very treatable if it’s low-grade. But I have even heard some bladder cancer experts refer to those low-grade, papillary, non-invasive superficial bladder tumors as bladder warts because just like warts on the skin, sometimes you treat them and they come back and you just treat them again, which is why those sorts of surveillance methods like cystoscopy that were mentioned are so important in that context.

Rebecca Johnson:

Thank you. And continuing with that… Oh, I’m sorry, Matt, did you want to add to that?

Dr. Matthew Mossanen:

No, that was great. I often will just tell patients that they’re really annoying. They’re like weeds in a garden. It’s going to come back, but it’s probably not going to harm you in the long run. So yeah, that was a great answer, I think.

Rebecca Johnson:

And Matt, since you’re unmuted here, and this will segue us into talking about non-muscle invasive. We received a question. After three or four years of non-muscle invasive bladder cancer with no recurrence, are continual annual CT scans recommended? Are they no longer needed? What is recommended in terms of surveillance?

Dr. Matthew Mossanen:

That’s a good question. No one size fits all answer. I think it’ll depend on the subtype of non-invasive disease, what risk category it is. Also, sort of on the history of what their initial diagnosis was, patient’s age, overall health. You sort of add all these things together. Typically, I’ll pursue about five years of imaging and then beyond that, it sort of depends on a case-by-case basis. There are fortunately some guidelines that give recommendations for each of the subtypes to help guide you, but I really do like to involve the patient and see what their preferences in terms of surveillance. I will say I do like to use MRIs now a little bit more frequently to try to reduce the amount of CT scans that we’re doing.

Rebecca Johnson:

Thank you. And I think we’ll keep talking about bladder cancer in the non-muscle invasive space for a little bit. We got many questions about treatments there and quite a few questions about clinical trials in the non-muscle invasive bladder cancer space. Given the current clinical trial landscape, Brendan, what treatments for high-risk non-muscle invasive bladder cancer are you most looking forward to coming to fruition or what’s looking promising?

Dr. Brendan Guercio:

Yeah. So it’s amazing how that space has kind of exploded in the past few years because there was really not unfortunately much going on there for a long time. And I think finally researchers and many groups have woken up to the fact that it’s a big unmet need that needs to be addressed for our patients.

Some of the things that are most exciting are things that have already been FDA approved but just are not very easily accessible right now like Adstiladrin which is a medicine that’s given in the bladder that’s basically a virus that’s designed to kill the bladder cancer and stimulate the immune system. Certainly looks effective but just hasn’t been very easy to get since it’s been approved for about a year. But I think it is becoming available now, finally. And then Anktiva is another medicine that’s designed to stimulate the immune system from inside the bladder that was recently approved. So I think those are great options.

There are some options like chemotherapy inside the bladder. Medicines like gemcitabine and docetaxel that maybe haven’t been studied quite as rigorously and had formal approvals, but definitely seemed to have efficacy and are really well tolerated by a lot of patients. And then I think there’s still a lot of other really exciting experimental things coming down the pipeline.

I think a lot of folks are excited about the, so-called pretzel systems like TAR-200, TAR-210. They are these neat little devices that urologists can put in the bladder that can very slowly release medicine over time instead of just putting it in for an hour every week or in the way we’ve often traditionally given medicines inside the bladder. And those slow releases, at least in the early studies that have been done so far, releasing medicines that are sometimes older but we’ve known that work well in other contexts like the chemotherapy gemcitabine or even the targeted therapy that I mentioned earlier, erdafitinib, which is already approved as a pill, but giving those slowly in the bladder using this new pretzel system, at least in the small studies that have been done, look really promising and interesting.

There are also IV medicines that are approved or being studied for non-muscle invasive bladder cancer too, excuse me. Like Keytruda or pembrolizumab obviously is an immunotherapy. That’s a standard option. Although, in all honesty, I think for the BCG unresponsive patients, the treatments that are used in the bladder seem to be probably similar in efficacy, although they’ve never been compared head to head to Keytruda. And they probably are better tolerated too. Even though most patients do pretty well on immunotherapy, it can cause serious side effects that are sometimes permanent in as many as 10% of patients or more. So I guess it’s a long answer, but very exciting area, and excited to see what comes in the future. But clinical trials are always a good option in that space, I’ll say because that’s why we’re getting so many good options for patients now.

Rebecca Johnson:

Yeah. It is really exciting. And I have two follow-ups to that information that you just shared. First, because we’re having so many newer treatments approved, and coming out of clinical trials, maybe we know about the efficacy but not as well about long-term effects. How are we finding out about side effects or how are patients being monitored on these newer treatments? And either of you’re welcome to respond to that.

Dr. Matthew Mossanen:

There’s an important study with John Gore and Angie Smith. That’s studying cystectomy versus bladder-sparing therapies for patients. And they’re using a tool called patient-reported outcomes. So validated questionnaires, standardized questionnaires to follow patients and figure out what their symptoms are like throughout this process throughout trying additional medication in the bladder or bladder removal, cystectomy, which is a really big deal for patients.

I think this study is going to be one of the most important studies that’s come out in a long time in terms of looking at patient quality of life with decisions of pursuing more treatment for bladder cancer. I think within a year, hopefully, there’ll be at least some preliminary data shared. And I think it will help us figure out what is the true toll that some of these therapies take on patients. A lot of patients undergoing intravascular therapy can be managed with medications, but there are a subset of patients that just have difficulty tolerating catheter-based installation of different agents in the bladder. I think it’s a case-by-case basis for each patient, but I would echo what Brandon said, which is usually it seems like intravascular treatments or treatments delivered directly to the bladder might be more effective but might come at the cost or the taxes of some side effects of the bladder.

Rebecca Johnson:

Thank you Matt, and thank you for mentioning that study. It is a really important study that I think will answer a lot of questions. I wanted to touch on one thing that you talked a bit about, which is the side effects of intravesical therapy. We did receive a question related to that. This question was specifically about bladder spasms post-BCG treatment, but can you talk just a little bit in general about what can a patient expect after receiving BCG treatment or another intravesical therapy?

Dr. Matthew Mossanen:

Well, it’s important to keep in mind that BCG is a bacteria. It’s a form of immunotherapy. And so it’s a controlled infection that stimulates the immune system. It will cause some symptoms that mirror those seen in a urinary tract infection. So patients that have bothersome bladder spasms, we can sometimes help mitigate or improve those symptoms with treatment with antispasmodics. Medications like Trospium or other kind of medications in that class can help.

We can also have patients sort of reduce a little bit of fluid that might contribute and make you have to go to the bathroom more frequently like caffeine or soda. Typically, before patients get BCG, we do have someone in our team talk to them about tips and tricks for dealing with BCG side effects. For whatever reason, there are a subset of patients that have no symptoms at all and get through BCG just maybe with a little bit of fatigue. And there are patients that have a very difficult time getting through therapy, and a smaller subset that even have to just stop further therapy. I don’t think there’s a good way to predict who will have which outcome, but I do think that symptoms can sometimes build up over time so you get the first dose and then once a week for six weeks. So I do have a lot of patients that by the fifth or sixth dose, the symptoms are worse than they were during the first or second dose.

I guess it’s a little bit off-topic, but one of the important studies that’s also coming out is studying, instead of using BCG upfront, we might be able to try something called gemcitabine and docetaxel. So that trial is currently underway. And I think those two things going head-to-head, it might sort of shift the paradigm of how we approach treating high-risk non-invasive bladder cancer. And in general, I think that gemcitabine and docetaxel is pretty well tolerated by patients for the most part, so that might also help improve the patient experience.

Rebecca Johnson:

Thank you. And Brendan, you shared a really nice summary on what we’re seeing coming out of clinical trials. Given all of those results, is BCG therapy still considered the gold standard of treatment in this space for non-muscle invasive?

Dr. Brendan Guercio:

I think for high-grade disease, BCG really is still the best option as far as we can tell. As was just alluded to, it hasn’t been compared head-to-head to a lot of the newer options that are becoming available, but we know it does work really well and gets a really great response in well over half of patients depending on their risk and disease features. And really, as mentioned earlier, it is one of the oldest types of immunotherapy to work really well in cancer and set the paradigm for using the immune system to fight cancer that we use so often with a lot of our newer treatments too. And maybe it will be displaced or augmented with other treatments in the future, but right now, if BCG is recommended, and as long as there’s not a shortage of it, which unfortunately can be an issue sometimes, I definitely think it’s a good option for many patients.

Rebecca Johnson:

I am spending a little bit of time on BCG because we did receive so many questions related to that as many patients will be treated with BCG. And so, Matt, can you answer the question? Does prognosis improve with repeated BCG treatments and how many treatments of BCG are recommended for a person with low-grade non-muscle invasive bladder cancer?

Dr. Matthew Mossanen:

That’s a big question. That’s a good question. We’ll try to dissect it out. So it is recommended to help reduce the risk that bladder cancer comes back. There’s good data for that. And maybe even reduce the risk that it will progress. It depends on what the patient’s original grade and stage is in terms of how long to treat the patient. But typically, after induction for higher-risk cases, we would recommend maintenance which is three doses given over three weeks, over a few years afterwards. The problem is that there isn’t enough BCG, and it has to be prioritized for patients that need to start their treatment and undergo the initial induction treatment, which is six doses in six weeks. And so because there isn’t enough and because we have to give it to the patients that need to sort of start their treatment or sometimes undergo a repeat induction, it means that the maintenance treatment is often disrupted and it’s not going exactly according to plan.

There’s an interesting study that came out that looked at two induction courses of BCG and showed that that’s also a potentially effective way to administer therapy to patients. Depending on the risk stratification of non-invasive bladder cancers such as patients with low-grade disease that might fall into the intermediate risk category, you could consider giving BCG or intravascular chemotherapy as an option. They’re both sort of guideline-approved. I think it depends on some of the specific features. Is it multifocal low grade? Is it a large low-grade tumor? Has it been a reoccurrence within a year? So putting all those things together, you can consider using it. But it’s such a scarce precious resource, it tends to be used in patients with high-grade high-risk disease.

Rebecca Johnson:

Thank you. And I did just want to ask, if BCG treatment is unsuccessful or other intravascular therapies are unsuccessful, Brendan, if you can comment on this question first and then Matt, I’d love to hear your perspective as well, how does the patient ensure that bladder removal is the last resort, which of course is the goal in treatment for every patient and physicians as well?

Dr. Brendan Guercio:

Well, I think actually the first thing I’ll mention, even as a medical oncologist, I would just say that sometimes bladder removal is the right answer. I know that can be really tough for a lot of patients to hear because a lot of people understandably want to keep their bladder if at all possible, which is a very reasonable desire. But removal of the bladder if BCG and other therapies in the bladder have not worked, does have a very high cure rate, and a lot of patients actually do have a pretty good quality of life after bladder removal once their bladder cancer-free.

There are some approved options and also clinical trials going on to try and help people keep their bladder in that situation. I mentioned pembrolizumab immunotherapy before, which is FDA-approved for BCG unresponsive disease. For patients who either can’t or do not wish to go through with a radical cystectomy to remove their bladder, that does work and have some durable responses in a subset of patients but it definitely is less than half of patients, and so a lot of those patients will still end up needing their bladder removed anyways unfortunately and do have some risk of the cancer progressing while they’re on the immunotherapy if it doesn’t work well. Although it’s probably not a very high risk if it’s still a non-muscle invasive disease, fortunately.

Hopefully, there’ll be more options in the near future to let people keep their bladders. I would definitely encourage participation in clinical trials with that aim since hopefully, that will advance the field so that more patients have those sorts of options.

Dr. Matthew Mossanen:

Well said. Only to add a bit to it, I think it depends not just on the motivation to keep the bladder, which is obviously a priority, but also on the patient’s overall health and that includes the health of the bladder, in other words, the bladder function. So an intact bladder with good bladder function is something that’s certainly worth preserving and exploring other options including clinical trials or emerging therapies. A lot of them that have been approved haven’t yet reached clinical practice like Adstiladrin.

I think for any patient exploring options after, for example, BCG has not worked, it’s important to have a discussion with a urologist that sees a lot of bladder cancer patients as they might have experience or access to clinical trials. And for many patients, I will also encourage them to speak to a medical oncologist if they do want to hear about pembrolizumab. Admittedly, we don’t use it that much where I practice, and the medical oncologists don’t seem to be too enthusiastic about it for non-invasive bladder cancer. But that being said, immunotherapy is a life-saving medication that can be very well tolerated. I think just making sure that you have a discussion with somebody that’s had that discussion with patients many times before is a key part of the decision-making process.

Rebecca Johnson:

Absolutely. Thank you both. And I do think that that question about bladder removal and your responses segue us into the next set of questions focused on muscle-invasive bladder cancer. We did have a question. Matt, if you can address this one. In someone with muscle-invasive bladder cancer avoid a radical cystectomy or removal of the bladder without having radiotherapy?

Dr. Matthew Mossanen:

Can they avoid surgery or avoid radiation? What was the question?

Rebecca Johnson:

I think can they avoid radiation prior to having their bladder removed or is it required, is it essential before a radical cystectomy?

Dr. Matthew Mossanen:

No. We would prefer that they not have radiation prior to surgery. Radiation can sometimes make the surgery more challenging. So if patients know that they’re going to undergo surgery, we would just consider neoadjuvant chemotherapy or chemotherapy before the operation and then proceed to surgery. In some cases, after surgery, you can consider giving radiation. And of course, as an alternative to surgery, you can always pursue chemoradiation, which is radiation with chemotherapy instead of taking out the bladder. But it’s not a standard practice to radiate the bladder prior to cystectomy or bladder removal.

Rebecca Johnson:

Thank you for providing that clarification. And Brendan, speaking of other non-invasive therapies instead of bladder removal, can you discuss whether there are non-invasive therapies such as therapeutic drugs or other technologies that are either in use or being studied in trials to reduce bladder cancer tumors and destroy cancer cells?

Dr. Brendan Guercio:

That’s a really great question. I think, in part, it depends on what we mean by non-invasive. Technically, chemotherapy is IV. Some people would not consider that very invasive. Radiation is X-rays, which might not be considered invasive. So certainly, there are some standard treatments that are not surgery that can potentially cure muscle-invasive bladder cancer without surgical removal of the bladder.

But in terms of, I think what obviously they’re asking about is not newer exciting non-invasive methods that might hopefully cause less side effects than those traditional modalities. There are a lot of interesting trials looking at using immunotherapies for invasive bladder cancer that have been done and are still ongoing. There are even some interesting studies that combine immunotherapy with modalities like ultrasound, which to my knowledge, that study is not reported out yet, but it’s certainly an interesting paradigm. High-frequency ultrasound has been established as something that’s potentially effective in very select cases of other cancers like prostate cancer, but really doesn’t have any standard role right now in bladder cancer.

And again, I think one of the most exciting non-invasive things in this space might also be the pretzel that I mentioned earlier that urologists are developing. There is some very limited data that suggests that it may even have some efficacy and muscle-invasive bladder cancer, although it probably would not be sufficient on its own. But perhaps, in combination with other treatments, it might help us preserve more bladders in the future, but it’s still very early days for that. We don’t have enough data to say whether or not that’s safe or effective yet for standard practice.

But I think antibody-drug conjugates like enfortumab vedotin are going to have a big role probably in the muscle-invasive bladder cancer space too with immunotherapy and those other agents, but the trials to prove that that’s a good option for patients that don’t have metastatic Stage 4 disease where it’s already a standard proof option, those trials are still ongoing. So we’re very excited to see what those trials show, but we don’t yet know the results.

Rebecca Johnson:

Thank you so much. And you mentioned EV and we saw some big trial results come out around EV Pembro. We received a question specifically related to that in the muscle-invasive space. And that was, do we know what percentage of patients treated with EV Pembro have ultimately elected not to have surgery or is it too early to know that, and what can you share about that treatment?

Dr. Brendan Guercio:

Yeah. Oh, go ahead, Matt.

Dr. Matthew Mossanen:

Go ahead. I was just going to mention that a lot of those treatments are being used in settings where surgery is not typically being considered because it’s metastatic. But as was already alluded to, I think these therapies as they show such promise in metastatic settings will then be used earlier and earlier in the disease. Brendan, go ahead. I know you’re about to mention something also about that.

Dr. Brendan Guercio:

Yeah. I was basically going to say exactly what you said. I guess I can add that we do have some very limited data in enfortumab alone for muscle-invasive bladder cancer. It was a small trial. I think only 20 patients who then got a few rounds of EV and then had surgery to remove their bladder to try and cure it. A very small study of patients but it was exciting that it did actually cause a pretty good response in the bladder with a response rate of around 40%, sort of similar to what we would expect with chemotherapy. And that wasn’t even with the combination of EV with pembrolizumab where we know it’s even more effective if you use those together. So definitely too early to use that as a standard treatment option in muscle-invasive bladder cancer right now. But just agree that we’re all excited to see what the clinical trials show that are ongoing, looking at EV with immunotherapy for patients with curable muscle-invasive bladder cancer and going through surgery.

Dr. Matthew Mossanen:

And to piggyback on that, one of the exciting parts of bladder cancer is that there is going to be a growth of new treatments and new opportunities for patients. I think one of the challenges is going to be, there’s going to be a lot of different choices. And it might not necessarily be clear which one is best. And so that’s why we’re going to need to rely heavily on very intelligent people like Brendan and medical oncologists that can really thoughtfully think about the data and decide which of these approved options is best. There are a number of research approaches in trying to predict which patients should get which therapy, but nothing yet has been clearly shown to be a useful and reproducible tool to help patients or providers pick the right treatment for the right patient at the right time.

Rebecca Johnson:

And that is actually a perfect lead-in to my next question, which was actually from a patient with advanced disease. And that is exactly, how do you make that decision with all these new treatments being approved and coming out, what are physicians now using to approach second-line treatment decisions and beyond?

Dr. Matthew Mossanen:

Go ahead, Brendan. I’ll go after you.

Dr. Brendan Guercio:

Sure. Yeah. That’s a million-dollar question. That is a very active area of controversy in the field. I think right now, at least, as far as standard options, the preferred first-line for most folks who specialize in the treatment of metastatic bladder cancer is pretty easy. At this point, it’s EV Pembro for patients that are good candidates for it. There are some people who may not be fit for it for certain medical reasons, but most patients are. But yeah, second line after EV Pembro, we don’t have any clinical trial data to guide us on what the best option is if a patient has already had cancer growth on EV Pembro because it’s such a new regimen. I think a lot of folks are kind of defaulting to using platinum chemotherapy as the second-line option just because that was our first-line option for so long. And obviously, medical oncologists are very comfortable with it and we know it does work and have a lot of efficacy in bladder cancer.

That said, I do know some folks who say if a patient has an FGFR3 mutation or fusion in their bladder cancer, they’ll consider using Erdafitinib, that targeted oral pill that I mentioned instead as a second-line option. Although really, the data that supports the use of Erdafitinib is all in the post-platinum chemotherapy setting, so I don’t think the majority of medical oncologists are doing that right now. I even know a few that say using sacituzumab govitecan, which is a different antibody-drug conjugate from enfortumab vedotin as a second-line option is reasonable. But that one has maybe a lower level of evidence because we don’t have randomized clinical trial data to support it yet. So I think the right answer is unknown.

Luckily, we do have good options in the second line that are effective. But which one is best is unclear. It might depend on the patient and their medical history and which medicine they might tolerate best. And really, we’re going to need clinical trials in the second line to help us better understand what’s best to use there first.

Dr. Matthew Mossanen:

I will just briefly veer off and just mention an interesting project that we’re working on to place a small device that’s kind of shaped like a bullet into the tumor that secretes different kinds of chemotherapy. And then if the tumor were to be removed, let’s say with cystectomy, you could study all of the different sort of geographic regions around the microdevice that has sort of secreted these different combination chemotherapies and potentially look at tumor growth or tumor cell death and potentially predict what would be an effective option.

It’s a really exciting project, but it’s only a project, and very, very far away from being able to be used reliably. But trying to think of innovative ways to help predict what patients should get, what treatment is the holy grail of cancer treatment. And so trying to figure out any way to get a little bit of light on is very important and obviously very useful. And it will only become more challenging because there’s a number of great therapies, and every time a new therapy comes along, they want to combine it with either the standard of care before it or another new treatment. So hopefully soon, we’ll have lots of great options and the biggest problem will be, choosing.

Dr. Brendan Guercio:

And I just wanted to add that, that’s the first I’ve heard of that new research project, but that sounds super neat, and I’m very excited to see what that shows.

Dr. Matthew Mossanen:

That is-

Dr. Brendan Guercio:

Thanks for [inaudible 00:54:01].

Dr. Matthew Mossanen:

… shamelessly my project. And I’m sorry for putting the plug in, but I couldn’t help it. It seems relevant.

Dr. Brendan Guercio:

All right. That sounds like… Personalized medicine taken to the next level, that’s great.

Rebecca Johnson:

Absolutely. It is exciting. And hopefully, that is the problem that we come to, that there are so many options that are showing promising results for bladder cancer patients. And so mindful of the time, as we come to the close, I want to thank you both so much for spending this time with us and answering these questions so thoughtfully that we’re really great questions submitted by patients and their loved ones. I think that we’re all grateful to you both for dedicating your careers and your expertise to advancing the bladder cancer field and improving patients’ lives. So we appreciate your dedication and are fortunate to work with you. So thank you so much.

Before we close, I do want to share with you the 2024 BCAN of Hope Award recipient. As part of Bladder Cancer Awareness Month, we asked members of the BCAN community to nominate that special individual who was their BCAN of hope and light in their bladder cancer journey. We received more than 80 nominations, and from those, we had three finalists. Bill Russell, a bladder cancer survivor and longtime volunteer with BCAN’s Survivor 2 Survivor program. Lydia Saravis, a bladder cancer survivor who leads an online support community that is open to all neobladder patients. And Dr. Jonathan Wright, the medical director of the University of Washington Neurology Clinic and UW professor of Urology. BCAN received a record, 2,017 votes, and it is my pleasure to announce that the winner of the 2024 BCAN of Hope Award is Lydia Saravis. Congratulations, Lydia. I understand she’s on the call this evening, so we’re very happy to have you here.

As I mentioned, Lydia is a bladder cancer survivor and someone who continues to give back to fellow patients and survivors. One of the people who nominated her said, “Lydia Saravis has sustained, grown, and facilitated a monthly Zoom support group now for scores of participants from around the world. She has brought experts from multiple disciplines to speak with the group, has helped dozens of prospective neobladder recipients become well-informed prior to surgery, and many more to adapt and adjust to their new diversion. Lydia epitomizes delivering on BCAN’s mission. She truly is a BCAN of hope.” So congratulations again and thank you for being with us this evening.

And lastly, just a reminder, that this program will be available for viewing on the bcan.org website in just a couple of days. This concludes our program. A special thank you to our experts, Drs. Mossanen and Guercio. I thank all of you for joining us this evening. Thank you so much for your support of BCAN and our bladder cancer community, and have a wonderful evening.