Webinar | Intermediate Risk Bladder Cancer: Understanding Your Treatment Options

June 3, 2025

Non-muscle invasive bladder cancer is divided into different risk categories based on size, location, and how likely it is to spread.  The risk classification system, which includes low, intermediate, and high-risk, helps guide your treatment options.  In this webinar, Dr. Joshua Meeks, Urologic Oncologist and Scientist at Northwestern University, explains the various treatment choices for patients diagnosed with intermediate-risk NMIBC.

Year: 2025

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Part 1. Intermediate Risk Bladder Cancer: Understanding Your Treatment Options

Transcript (PDF)

Part 2. Intermediate Risk Bladder Cancer: Understanding Your Treatment Options

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Part 3. Intermediate Risk Bladder Cancer: Understanding Your Treatment Options

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Part 4. Intermediate Risk Bladder Cancer: Understanding Your Treatment Options

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Full Transcript of Intermediate Risk Bladder Cancer: Understanding Your Treatment Options

Stephanie Chisolm:

Today’s webinar is Intermediate Risk Bladder Cancer: Understanding Your Treatment Options. Navigating a diagnosis of bladder cancer can be really overwhelming. Non-muscle-invasive is just as overwhelming as muscle-invasive, and there’s so many unknowns. When I started at the Bladder Cancer Advocacy Network 10 years ago, you were either diagnosed with low-risk non-muscle-invasive bladder cancer or high-risk. Nobody talked about intermediate risk.

So today, BCAN is delighted to welcome you to an engaging and informative webinar with Dr. Joshua Meeks, a urologic oncologist and scientist at Northwestern University in Chicago. Dr. Meeks has almost 20 years of experience in the diagnosis, treatment, and management of bladder cancer and has completed many, many, many research projects specifically focused on bladder cancer. He received his medical and PhD degrees from Northwestern University in 2005 and completed a urology residency at Northwestern in 2011, a urologic oncology fellowship at Memorial Sloan Kettering in New York in 2012.

He’ll provide a comprehensive overview of treatment options specifically tailored for patients with intermediate-risk, non-muscle-invasive bladder cancer. So remember to add your questions to the Q&A box at the bottom as you think of them, and we’ll answer them at the end. Dr. Meeks, I’m going to turn it over to you, and I’m looking forward to your presentation.

Dr. Joshua Meeks:

 I was really excited that you asked me to do this, because I agree with you totally that the whole group of … We call it intermediate risk bladder cancers, and the first thing we’re going to do is talk about what that actually is. But it’s such a patient-driven concept. I have a lot of folks I care for here in Chicago that are intermediate risk. The great point you made is that for each of our patients, that cancer is the most critical thing in their life, and it’s not fair to do a comparison of life-threatening or non-life-threatening. When I’m with somebody, and we’re talking about where they are in their journey, this is the most critical thing to them. What I’m excited about is that there’s so much coming on the horizon for this group of folks, where I’ll tell you, five years ago, I had very little to offer them. So again, I think this is a really exciting space, and I’m so happy that we’re addressing this today.

Here are my disclosures, and again, I think much of this has to do with trials that we’re going to be talking about, because … I think, again, it calls attention to the fact that our partners in pharma are interested in this space, because a lot of this involves intermediate risk.

So I’m going to talk today about intermediate risk, how we define that, and then, what are our outcomes and expectations for patients with intermediate risk? We’re going to talk about how I approach them and what the standard of care is, and then we’re going to talk about treatments. I think the exciting part’s at the end, because again, there’s a lot more in the space that’s developing.

Dr. Joshua Meeks:

All right. So intermediate risk and how we define that.

So first question people ask is, “What actually is this?” And so to put a tumor in intermediate risk or to say that a patient is intermediate risk, we need information from the TURBT. So what you’re seeing is a video of what a TURBT looks like. This is the surgery itself. And so as we’re doing the surgery, the clinician needs not only the pathology, that will come, but also, in general, recording the size of the tumor and the number of tumors. That’s what we get from the surgery. So the surgeon, as … If you ever read an operative report, that information is usually described there. Then, that’s combined with the pathology report, and together, we’re able to establish a risk classification.

So this is often hard, because when, usually, I meet somebody, they want to know, “What’s the next steps after surgery?” But really, we can’t do that until after the surgery’s done. We know what things look like at surgery, and then we get the pathology report. So putting all that together, we’re able to come up with a risk status.

And so there’s really basically three risk status that people use. This is from the AUA because we’re urologists in the US, so it’s the American Urologic Association. Really, the AUA has set up three groups, and I kind of lump these into four major characters here.

So the turtles of bladder cancer are the low-risk tumors, and generally, they’re pretty slow-growing. That’s why we call them the turtles. They’re low-grade tumors, single tumors under three centimeters, so very small. I think this intermediate-risk group we’ll talk about is bigger low-grade tumors, tumors that come back within a year, multifocal, meaning they’re in more than one area. In the US, we say that a high-grade tumor under three centimeters is considered intermediate risk, and then the high risk is everything else. Those are much more like … I would consider them sort of the wolves of bladder cancer in that they tend to be more aggressive. You have to worry about them more.

Then, there’s sort of the bears that are kind of the apex predator of bladder cancer that I worry about a ton. Again, we’re not talking about those today, but that’s more patients … tumors with lymphovascular invasions and variant histology. But again, today, we’re talking about those, the rabbits or the intermediate risk.

Now, this is very clinical. This is just to show you that there are three different kinds of classifications, and I kind of wanted to spend a second on that.

Dr. Joshua Meeks:

And so to hit the easy button and to say, “How do other people around the world think about this?” they basically say, “Okay. There’s low-risk patients.” So Stephanie kind of talked about those. Those are low-grade small tumors, individual, single ones. That’s low-risk. High-risk is anything high-grade, anything Stage I, anything with carcinoma in situ. That’s all high-risk.

Then, intermediate is everything else. So it’s a big group of patients, and I think there’s a lot of value to this even though we don’t use this specifically in the US. But I think that kind of fits this group. So basically, we’re talking about recurrent or multifocal low-grade cancers that keep coming back. When I think about these, these are usually patients that I work with that are extremely frustrated by their cancer, that, again, even though it’s not life-threatening, these are cancers that keep coming back, and we just don’t have a great solution for them. So again, recurrent or multifocal low-grade cancers. Okay?

Dr. Joshua Meeks:

And so what do we expect? We talk about recurrence, and so I kind of want to be very clear about our outcomes here.

Dr. Joshua Meeks:

So we have recurrence, which means a tumor coming back at all. Most of the time, it’s going to be those same low-grade cancers. That’s a recurrence. Progression is when things are getting worse. So that’s usually either a high-grade tumor or an invasive cancer, but that’s a more concerning outcome. So when you look at these outcomes, that’s a Kaplan-Meier curve, and so if we start off with a 100% of patients, that’s when they start after surgery, you can see that by a year, about 14% of those patients will have had a recurrence. This is without therapy.

By three years, over 38% have had a recurrence. And so in general, by the time you get out to about five years, it looks like about half of patients have had some form of recurrence. Now, that’s most of the endpoints that we’re worried about for intermediate-risk bladder cancer. It’s the tumor coming back. And so I think the first thing I try to talk to folks about is this is often not a cancer that I don’t anticipate it’s going to take your life. So if you look at progression, by five years, the risk of that is about 2%. So folks are very unlikely to die of this cancer, but it doesn’t mean there’s a significant burden of recurrence.

So recurrence in these cancers are, again, about 50% at five years. So it is a cancer that will come back, and that’s where our strategies are really aimed towards decreasing the risk of tumor recurrence. Again, progression, luckily, is a relatively rare phenomenon, and that certainly can happen. But really, what we’re trying to do is keep people cancer-free. And so that’s the endpoint that matters the most in this field. Does that make sense? I think that’s a critical thing for this cancer, is this cancer is about getting good, long disease-free intervals, and obviously, cure in this case means cancer not coming back.

Dr. Joshua Meeks:

Now, a lot of that comes down to some of the challenges in this group of patients, because it is a pretty heterogeneous cancer, meaning that there’s a lot of variability. So in this line, again, we’re starting with a hundred percent of patients starting at time zero, and by the time we get out to five years or 60 months, there’s a big split there. The difference in these two lines is grade. So we kind of have gotten rid of grade 1, 2, 3, but this is an older system, where it’s Grade 1 versus Grade 2. You can see that by going up to Grade 2, the rate of recurrence is significantly higher. So again, that kind of goes back to some of the variability in this group of patients.

Dr. Joshua Meeks:

Now, I think the big challenge for us as providers and what we try and talk to our patients about is that there’s a wide spectrum of cancers in this space. So how do you individualize that to get to kind of a Goldilocks point, where you’re not overtreating everybody? Because you could treat everybody and give them the most amount of therapy, but you’re probably providing a lot of treatment that people don’t need and making people feel worse. Alternatively, there’s a lot of people who are going to recur, and some of them will progress. So is there any way to tailor that where we’re coming to every patient and saying, “What matters the most to you, and what are the endpoints that matter to you? How do we make this individualized?”

Dr. Joshua Meeks:

That’s kind of where we’ve tried to evolve as providers for our patients. Again, I credit Dr. Kamat and the IBCG for this classification, because basically, if you look at all the possible tumors that are involved in this group, we’ve tried to set up, or he’s tried to set up a point system in order to put people into zero, one to two, or more than three risk factors. And so when I’m trying to talk to a patient about where they fit, we sort of go back to this almost every time, and I’m going to kind of do a summary at the end.

But here are the factors that we think matter. So are there multiple cancers, meaning in different parts of the bladder affected? Have they had an early recurrence, meaning that within the first year, have they had more than one recurrence? Are they having frequent recurrences, so more than one tumor a year? Is the size of the tumor bigger than three centimeters? Have we previously treated them with something, and they’ve not had a complete response? So each one of those is considered a point or a risk factor, and then, based on that, we can sort of put people into no risk factors, one to two, or more than three. This is actually a pretty straightforward system to do, and again, I don’t think this is information that you would say, “Oh. Well, you’re a three. You should do this.” But I try to … As you’ll see coming forward, this really helps to put people into different risk groups and really provides information about what we anticipate the next year is going to look like.

Dr. Joshua Meeks:

So again, we have three risk groups, and this is kind of how those risk groups pan out. Again, these are Kaplan-Meier curves, so we start off at a hundred percent, where everybody’s doing great. Then, we start to have events. And so you can see that the blue line, the line on top, they’re having fewer events, and then the green line, that’s the folks with more than three risk factors. They’re having more events. And so if you look at the outcomes, that if you have more than three risk factors, you’re more than twofold likely to have an event. And so again, at five years, for high risk patients in this dataset, it’s almost 80% of people have had a recurrence, and up to 17% have had progression.

So again, I think this is an important thing as far as counseling and thinking about where people are and why we, for example, want to escalate some versus others. Again, it provides some reasoning for that. I think that’s an important part. Stephanie, is that clear? Do you think that makes a lot of sense, and do you have any thoughts about this?

Stephanie Chisolm:

I do think that makes sense. I have a question. You mentioned something about recurrence, early recurrence is within a year. So what about those people that have a new tumor every 18 months? If they’re consistently doing that, is that another thing that should be counted?

Dr. Joshua Meeks:

Yeah. That’s an interesting group. I have a discussion with folks, because it is always like, “Well, you’re just over 12 months, and so you’re not … technically don’t meet the definition of intermediate risk.” I actually think they may be a little different, and I don’t really know where to have that discussion. In general, if you look back to our point system here, they wouldn’t really get any points from that. So they kind of would be in zero.

Dr. Joshua Meeks:

And so if you look for the zero point group folks, they get the single installation, and you follow them.

I tend to think if you can make it more than 12 months, which, again, would be two cystoscopies with no recurrence, in general, those folks usually do pretty well. I tend to, personally, at least, I tend to offer them more just like the fulguration in the office and would really probably not escalate them to treatment unless they said, “I just can’t deal with this.” So technically, if it’s a little bit more than a year, they’re probably doing well, and in general, I try and do less is more in them.

Stephanie Chisolm:

Okay. But if they did say, “I love you. I love seeing you, but I hate coming in here and having this procedure every other year. Is this something we can do something a little more substantial to keep the cancer from coming back?” is that where perhaps they could be offered one of the treatments that you’re going to discuss a little bit later?

Dr. Joshua Meeks:

Oh. Yeah. Absolutely, Stephanie. So you could offer them intravesical therapy. I think the concern for that, though, is once you get to … We don’t really have a way to individualize that where they’re not getting a year of treatment. So generally, we’ll talk in a bit about our treatment regimens that we offer for intermediate risk, and that’s, in general, about 15 doses. So when you compare a scope and office-based fulguration, which would happen maybe once a year or once every 15 to 18 months, I think the burden of that is much less than coming in for 15 doses of therapy over the course of a year, so especially if people don’t tolerate it.

So I usually really try to deescalate, but if they wanted therapy, I’d say, “Well, why don’t we just do six, and see how you feel, and see how it works.” I think one of the things that we’ll talk about is the chemotherapy, while we’re making decisions to escalate to chemotherapy, not only is it not a free ride, but it’s also not been the most effective. It’s not like we’re offering people going from a 30% recurrence rate to zero. With the best therapies we have, one of the challenges of these tumors is that, and this is kind of, again, where my scientist cap goes on, they’re not that much different than the normal bladder lining.

So a lot of the therapies that we’ve developed, and the reason, for example, that you talk about high-grade and high-risk is that our therapies work better in those cancers, because the tumor has different biology than the normal bladder lining. Many of these tumors, biologically, are pretty similar. So I think some of the challenges is finding the best therapies for them. Now, if we have therapies that are very, very effective with less toxicity in the future, that may really change how we look at this.

Stephanie Chisolm:

Yeah. I don’t know that anybody’s got to that point yet where there’s less toxicity in terms of potential for side effects or irritations and things. So okay.

Dr. Joshua Meeks:

Well, we’ll get there.

Stephanie Chisolm:

Good points. Good points. Yeah.

Dr. Joshua Meeks:

I think there may be some we’ll get to at the end that are maybe pretty close.

Stephanie Chisolm:

Okay. Good.

Dr. Joshua Meeks:

All right. So I just wanted to mention this. So again, this is the number of risk factors as columns and then the chances of having progression, and again, the only point I’m making with this is as the number of risk factors go up, the risk of progression gets higher. So again, those are significantly different, suggesting that the classification is helpful, and it’s important to talk to people about what they expect.

Dr. Joshua Meeks:

Okay. So what do we do for folks with intermediate risk?

Dr. Joshua Meeks:

I think a lot of the lion’s share currently comes down to the procedure, the TURBT or the transurethral resection of bladder tumor. I showed you a short clip of what one of those looks like. So the biggest point of that is that we want to get everything completely removed at the time of surgery. So in most cases, that’s going to be an anesthetic. It’s going to be a tumor removal, and I do think there’s a benefit to trying to use a single dose of chemotherapy in the operating room. Now, you can argue, are there some nuances to that? Is there a role for blue light or NBI?

Stephanie Chisolm:

That’s why I just turned my camera on.

Dr. Joshua Meeks:

Yeah. I mean, I think that’s going to be very individualized, and that’s kind of where providers and patients need to have that discussion. I use it, and the reason I use blue light cystoscopy is you’ll be shocked how many very small tumors that you find that show up, and the same is true with NBI, that will be there that you won’t see. It’s different than carcinoma in situ, where you’re looking for flat lesions. These are very small papillary tumors that you just don’t see them very well, because they’re so small. If I see them, I’ll either biopsy them or fulgurate them.

Again, those change your number scores, right, because now, you’re potentially looking at multifocal tumors. But my goal in that surgery is to visually clean anything out that looks like a potential bladder cancer, because I worry that they’re going to come back. So anything I can do to reset the clock, in my opinion, makes sense. Now, there’s randomized trial data. When you look at intermediate risk, and they compare patients who got blue light versus those who didn’t, there’s no difference in outcome. There’s a lot of things you can talk about that study. I think there’s things that contribute to that. But the way I kind of see it, personally, is that if someone’s willing to go to sleep to have a surgery, I want to do the best surgery I can, and this makes me potentially do a better surgery.

I also think that if it’s negative, that’s also important. Right? Because that means there’s fewer things that I saw there. So I do like, I personally like enhanced cystoscopy. I think a AUA and IBCG recommend adjuvant chemotherapy. That’s probably going to be gemcitabine at most places. So that’ll be put in the bladder at the end of the operation for two hours. There is potential to send the cells from that. So that’s a cytology if someone’s had a cytology that’s positive before. So TURBT, chemotherapy, maybe a role for enhanced cystoscopy. Stephanie, what do you think?

Stephanie Chisolm:

I think that makes sense. Unfortunately, a lot of patients say, “My doctor doesn’t have the blue light.” So that seems to be a problem. We hear that from a lot of people, and I know that they’re working to add blue light everywhere. But it’s a process. It’s a big deal to make a commitment to that. So it’s great that you’re able to use that.

Dr. Joshua Meeks:

Again, I don’t think you need to be brand specific. NBI is Olympus’s enhanced cystoscopy platform. It’s a flick of a button. It’s in many cameras. It’s very good. It shocked me how many cameras have NBI, and people don’t know it. So I think that’s another way to do enhanced cystoscopy. I don’t know that I would move providers to find someone who has blue light, but I would say that in general, a lot of places that take care of a lot of bladder cancer tend to have enhanced cystoscopy available to them. We kind of want-

Stephanie Chisolm:

Okay.

Dr. Joshua Meeks:

Yeah.

Stephanie Chisolm:

So NBI is the narrow band imaging. Right?

Dr. Joshua Meeks:

Yes.

Stephanie Chisolm:

So it’s a different wavelength. So it’s actually showing more of the vascularity that-

Dr. Joshua Meeks:

That’s right.

Stephanie Chisolm:

Obviously, tumors need a lot of blood flow, and that’s how it’s showing more of … Under the surface, you’re seeing that blood flow, and that’s how you would know with the narrow band imaging?

Dr. Joshua Meeks:

That’s exactly right. It’s in the camera head. So one of the benefits of NBI is that you don’t need a catheterization ahead of time. I’ll tell you that I try to always talk to folks that are going to get blue light, that, “We’re going to do a procedure. You’re going to get a catheter. You need to hold it for an hour.” One of the benefits of NBI ahead of time is that you don’t have to do that. So there’s pluses and minuses for each. Our guidelines recommend both.

Again, I think talking providers, and physicians, and what they think, and what matters to them, I think that’s an important part of that, that pre-surgery discussion about, what are we doing the day of, and why do we do that? I always recommend people talk to their providers. Right? And so everybody’s on the same page.

Stephanie Chisolm:

Yep. Great. Thank you. Keep going. You’re doing great. Good stuff.

Dr. Joshua Meeks:

All right. So this is, what do we do? This is kind of a complex table. Let me try and break this down very simply. So how often should people be getting cystoscopy imaging and urine tests? So very clearly, for imaging, it’s all over the place. I still think people need at least annual imaging. Why do I think that? Really, we can have stuff show up outside the bladder. We do a good job of looking in the bladder, but we miss stuff outside of it. The only way you find that is by doing  imaging. So I usually recommend annual imaging, and I offer it to everybody. So again, our guidelines say one to two-year intervals. That’s a discussion.

As far as cystoscopy, the AUA makes it very simple. They put everybody in one bucket. They say three months, then three to six for two years, then six to 12, through years five. So basically, it’s kind of like everybody gets a scope every three months for two years. Then, between years two and five, it’s usually every six. So that’s the AUA. And so that’s probably the simplest for people to understand. Again, here we go to the IBCG. Here’s your risk factors. For zero risk factors, they say three, nine, and annually. So it’s much less. If you have one to two, it’s three, six, 12, and then every six months. Then, for more than two, it’s basically back to every three months for two years.

So again, we’re getting to precision. There is a value in doing these risk factors for folks, because again, you can escalate or de-escalate based on where people are clinically. So that’s another reason why I think it makes a ton of sense. Again, this is a discussion. I’ve had folks say, “I want a more intensive evaluation, but I don’t want therapy.” I think that’s fine, but again, it’s really important to have these discussions.

Dr. Joshua Meeks:

Okay. I think an important thing to talk about is that first three-month cystoscopy and why that matters so much. So overall, six and a half percent of people are going to have a recurrence at that first cystoscopy, and if you’re negative at that first cystoscopy, very few are going to have that at 12 months. So if you have a recurrence at that first scope at three months, that’s almost a fivefold increase risk of progression. So that’s why that first three-month one is so important, and if it’s negative, you’re in a much better spot. So either way, I think that first three-monther is really important, and again, it’s really important to kind of start thinking about what’s going to come down the road. Okay?

Dr. Joshua Meeks:

All right. So therapy. So again, we’re in intermediate risk, so a lot of folks are going to get treatment. In general, we recommend starting that between two and six weeks after surgery, and it’s all risk-based. The AUA would say that everybody should get either chemotherapy or BCG. So with that said, at Northwestern, we have some BCG but not a ton. So for the most part, I’m going to start most patients on chemotherapy, and if they have a recurrence on chemotherapy, then I’ll escalate to BCG. That’s kind of using AUA.

If you sort of look at risk stratification, you could say with no risk factors, you do nothing. One to two, you would consider chemotherapy, three or more, BCG. Obviously, this is the starting point for discussion. I have a lot of folks that say, “Well, why can’t we just do BCG?” Part of that has to do with we don’t have as much as we wish we did, but if we do have more than we can, that’s very reasonable to talk to folks. I’ve had people leave our group and go to other places where there is BCG, and that’s perfectly acceptable. But I think kind of looking at that and realizing that there’s three potential roads and a lot to talk about certainly lets us escalate.

Dr. Joshua Meeks:

All right. So what do we expect for therapy, and why are both possible? Well, because the outcomes are essentially the same for intermediate-risk bladder cancer.

So again, these are two curves, again, starting at a hundred percent. We get to around 50% recurrence rate at four years, so no real difference between BCG and chemotherapy when we look at rates of recurrence. This is a little bit of an old study. This is from 2009.

Dr. Joshua Meeks:

Looking at more contemporary data … This is, again, from Dr. Kamat and I think some of the group at Rutgers looking at BCG and then gemcitabine and docetaxel, and I think this is more what you would anticipate. On therapy, the rate of recurrence is about 15 to 20% at a year and goes down to, again, around 30% at two years. So here’s that data. Again, no real difference between these two, but I think this goes to show you that using our most aggressive therapy, still about 20% of people on treatment are going to have or experience a recurrence at 12 months, and about 30 to 35% or so by two years. So even with our best treatments, I would say we’re falling short. And so this is really where some of the frustration has been up until now, that we’re giving you treatments that we would normally give high-risk bladder cancer, and the response rates are somewhat better. But this is a much lower risk of bladder cancer. So is that really that much better?

And so I think that’s where we can kind of start shifting to, what’s new in 2025 where we didn’t have this before? Stephanie, just any thoughts from your end as far as our treatments and frustration that you hear? Because I think that providers and pharma have kind of heard that, and that’s what’s led to this sort of newer group of therapies.

Stephanie Chisolm:

Yeah. I do think that, because not everybody responds to BCG. When it does work, it’s great. It does, as you mentioned, it’s got six weeks, and then you’ve got a maintenance and all the other aspects of it. So I do think that the community is welcoming some of these new options, and I’m really excited for you to be sharing that information about what’s coming down the pike, what we expect to see. Hopefully, approvals will be coming in the next quarter maybe. It’s very exciting.

Dr. Joshua Meeks:

Because, again, when you look at this data at 12 months, I would say for high-risk bladder cancer, it would probably be like 5% lower. So in high-risk bladder cancer, you’d think it’s about 75% at 12 months. So these are low-risk cancers, and they’re not much better. Those confidence intervals are not that different. So I think that’s what’s frustrating from a provider perspective, is we go through all this decision making to say, “Are we going to start treatment or not?” Then, when we start treatment, it’s not like it’s like it always goes away. Right?

I think that’s the frustrating part, is that we have a lot of therapies that work about the same for high-risk bladder cancer, and you would think with the risk being different that you would have better therapies.

Dr. Joshua Meeks:

So that kind of is the step to kind of like what’s coming and why I am extremely excited about this field, because I think for the first time, we can say, “I have something different to offer you.” And so the first thing is TAR-210.

Dr. Joshua Meeks:

And so the first thing is TAR-210.

Dr. Joshua Meeks:

And so, um, TAR-210 here’s a nice sort of visual about how it’s deployed. It’s a device that’s put into the bladder and it comes in as a tube and then curls up like a pretzel. People call this the pretzel, um, and now everything I’ve talked about before is really, um, like a wash. So we put it in your bladder. You hold it for two hours, and then you pee it out. You know, the erda- this pretzel is a device that goes in, and this one stays in for three months. The picture, the video is the other gemcitabine-eluting one, so the colors are a little different. But, you know, the key thing about this and why it’s so cool is that this is a therapy that started as a pill. We tried to give it in a pill to people with advanced bladder cancer. While it worked, um, there was a lot of toxicity, cause it goes throughout your whole body.

So then, J&J was very bright to develop this in something that goes right into the bladder. You get rid of all the toxicity, and you get local therapy. Um, and the cool thing is that many of our early bladder cancers, actually many more, in the neighborhood around 65 to 70% of early stage bladder cancer, intermediate-risk, have an alteration that’s directly targeted by erdafitinib. So that FGF receptor mutation, again, is much more common in early stage bladder cancer. Um, and the response rates are very good, and the therapy is very local. And so that’s where a lot of us are incredibly excited about this therapy that’s there for three months, and it seems to be very specific for their bladder cancer. Um, so, I just want to talk a little bit about the data and try and summarize that as well as I can. So I-

Stephanie Chisolm:

May I just ask a quick question first?

Dr. Joshua Meeks:

Yep.

Stephanie Chisolm:

I just want to ask a quick one. Um, how often do you take the tumor, when you remove it with the TURBT through fulguration, and you’re taking that tumor out, how often, with this non-muscle-invasive, do you get it tested for these genetic mutations like the FGFR that is what would react better to erdafitinib?

Dr. Joshua Meeks:

So, uh, evolving question. Up until now, we’ve not been doing it, and the reason for that, Stephanie, is that we’ve never had a reason to do it, cause I don’t have anything specific for it.

Stephanie Chisolm:

Got it.

Dr. Joshua Meeks:

But now that we have a target, and now that we have something to do specific for those patients, um, you know, I think that that’s going to change.  And there’s two ways to do that. One of that ways is to go get a piece of the tumor and then send that off. The other is a urine test.

And so, um, you know, in this first in human trial, we did both. We did both urine and tissue, and it’s not perfect, meaning that like just because you have it in tissue doesn’t mean the urine’s going to be positive. There’s some that are positive in one versus the other. But, if you, the good news is that when we look at the results..

Dr. Joshua Meeks:

Which is here, it didn’t matter how you tested positive. The response rates were just as good.

Um, the other thing that may be worth questioning, in, for example, in this study, uh, patients didn’t have their tumor resected. So they had a tumor, and the device went in. So this is an ablative therapy here. Um, and so, uh, that’s also very exciting, because you think about trying to decrease the number of procedures that people had. Because that’s one of the huge burdens for intermediate risk, is a lot of surgery, you know, a lot of endoscopy, a lot of procedures. A lot of, whereas this device, when it goes in there, it can just ablate the tumor. Um, that’s at least what this data suggests.

So these are swimmers plots, and you look at the time points at the bottom. And so, again, you have a 90% complete response rate at 12 weeks of these tumors that were ablated. So all of these, uh, patients started out with tumor that just went away. And so, you know, again, overall 100% of patients achieved a clinical response. So that’s really amazing, and then when you look at the duration of response, that’s hitting 89% at, at, nine months. So I think this is a really exciting change to this field. We know a major target, again, found in anywhere from 60 to 70% of patients, and the duration of response seems to be very, very good.

Stephanie Chisolm:

Great. Um, this is a device. The pretzel itself is a delivery mechanism. Right? So they can also use it for other things, like chemotherapy and other medicine that can go into that device?

Dr. Joshua Meeks:

Yeah. So again, this is sort of J&J’S pipeline. So, um, the question would be how it’s engineered. I mean, they’re incredibly smart people and great to talk to about you know, what you could do with this, but yeah. The pretzel is the shape, and when you actually … If you ever get to see one up close, there’s little small pellets of medication in there, and you’re right. Your mind starts thinking about what else you could potentially put in there, you know, as far as medication delivery, and it, it makes sense that you have something that’s there all the time as opposed to hold it for two hours and hope it works. Um, this just sits there. Now, I think the downside is, and I don’t know that I have a tolerability slide.

Dr. Joshua Meeks:

I don’t, but, but, you know, there are people who have a little more bladder spasm with this. So I think, you know, again, it’s not going to be perfect for everybody, and if you have bladder spasms with it, we’re learning how to try to manage that. But, but, some people are going to need breaks, um, and we may have to figure out how to do that. I wanted to just show this. This is like looking at blood versus urine concentrations. And so if you look at the blood concentrations, the red, and blue, and black lines are the two different doses. If you compare those to the urine concentrations, you know, again, we’re looking at 40 on the blood, and in the urine, you’re getting in the one to 2,000 levels. So the dose is very, very high in the urine, meaning that the drug is working great in the bladder. So it’s, you know, 50-fold lower in the blood than it is in the urine, and that’s why you’re getting the response without the toxicity.

Stephanie Chisolm:

That makes sense when you have that non-muscle-invasive. It really is on that inner lining. So getting it into your bloodstream is not as important, because the odds of there being a cancer cell somewhere else are very slim. So yeah. That makes sense.

Dr. Joshua Meeks:

And so this is the trial that is ongoing with this now, and this is, you know, a really important trial. So again, this is FGF receptor positive patients. So we’ve tested their tumor, and it’s comparing chemotherapy, which we’ve talked about, that’s a standard of care, versus TAR-210. And it’s 270 patients in each arm. Uh, this is, you know, big trial, uh, enrolling now. So we’re excited to see, like, is it better? Right? And the question’s going to be, how long can people go without tumors in comparing these two drugs, two, two, treatment options. This is how this new standard of care becomes available, um, is that we compare these two. And so this is ongoing. This is called MoonRISe-1. There’s more MoonRISEs coming, but I think this is a really exciting uh trial in this space and we’re really going to be excited to see what it shows.

Dr. Joshua Meeks:

UGN-102. So this is another therapy. And so, uh, the really neat thing about this for our patients is that this is an ablative treatment. So the hope is with this, that, again, we can spare patients from TURBT.

Dr. Joshua Meeks:

And so the way that this sort of was tested, again, uh, this is the ATLAS trial, so, um, I’m just showing you this so you have a sense of comparison. So this was UGN-102 compared to TURBT. And then if patients had tumor, they could then undergo a TURBT in the UGN-102 arm. And so this is a chemotherapy.

So we talked about mitomycin, and in general, the way that’s administered in our clinic is you come in, we put a catheter in, the therapy gets put in, you hold it for, you know, 60 to 120 minutes, and then you urinate it out. This is, you know, more forms of solid gel in the bladder, and it’s urinated out much longer. So it’s in the bladder for a much longer duration of time. And so because of that, this is the … If you know about Gelmyto, that’s what’s used in the kidney, this is … UGN-102 is a very similar version of that, but, but used in the bladder.

And so this is, again, some of those Kaplan-Meier curves comparing UGN-102 versus TURBT rate and even though the response is about the same, uh, when you look over time, you know, people with UGN-102 have less events, and they do much better over time. So this was the ATLAS trial that was published.

And then this led to a single arm trial. This is ENVISION, and again, this is UGN-102, single arm trial, given weekly for six weeks. And then, how did the people do at three months.

Dr. Joshua Meeks:

And so looking at response rate, 80% complete response rate of almost 200 patients. So that’s really good.

Dr. Joshua Meeks:

So 82.3% with um, remained disease-free of those 90%. So, so again, um, the hope here is that … Is this going to work for everybody? Hard to know. But we have another therapy for people that, you know, before, are just tired of getting procedures, tired of getting fulgurations, and you’re looking at durability of response of 82.3% when you get those um six doses of UGN-102. So I think that that is a real option for folks. I mean, again, it’ll be really nice to have more than one option.

Dr. Joshua Meeks:

And you could see why this would be very good for patients because again, if you look across the board, the consistent response rate at three months is somewhere between 65 and 80% of tumors that just go away without the need for a, for a TURBT.

Stephanie Chisolm:

Yeah.

Dr. Joshua Meeks:

Do you, are you hearing that?

Stephanie Chisolm:

It’s great because-

Dr. Joshua Meeks:

Yeah.

Stephanie Chisolm:

Yeah. I think, again, that’s also sort of what you get with BCG in the high-risk. It’s about 65%, roughly. Right? And so the idea to be able to have that medicine stay against that tumor for a longer period of time makes more sense to be able to have that reaction to get rid of the cancer.

Dr. Joshua Meeks:

Without needing a TURBT, and, and again, some of it is like preference. But as you know, there’s a lot of folks that we see that are just not well. And so trying to get the surgery, and stop blood thinners, and you know, … Even, even, you know, there are, as you know, there are no small surgeries. So, um, if, if. there’s a reason to try to avoid that, I think there’s also a concern of, you know, how could this be portable? Can this be done well without … as a procedure first? So I think there’s a lot of interest in this going forward.

Dr. Joshua Meeks:

The last thing I’m going to talk about is CG007, or cretostimogene,

And again, this is a pretty, really interesting sort of future-thinking kind of therapy.

And Again, this is a therapy that’s put into a viral vector that finds its way into bladder cancer cells. It causes the cells to, to replicate and die, and then that causes more immune cells to come.

So, there is some specificity to that, because it doesn’t seem to replicate in normal cells and only replicates in, in bladder cancer cells. So there is some precision involved in that.

Dr. Joshua Meeks:

And, and so this is their Phase III trial. This is what they call PIVOT-006. It does allow some high-grade tumors, but again, it’s comparing TURBT to intravesical cretostimogene, six weekly doses followed by three doses at three, six, uh, and 12 months.

So I think, again, this is a really new and innovative therapy. It seems to have really good outcomes in, in BCG-unresponsive folks. And then, we’re moving this early into intermediate risk. And so I just think about if you look at these three alone, um, there’s so much promise here to be able to offer patients when they say, “I’m tired of having this cancer that keeps coming back. What do you have?” Uh, and, they’re all different. Right? So you’ve got a viral therapy. You’ve got a ablative gel, and then you’ve got a device. Um, and so, you know, it’s just so many more options that we, we have in the future, potentially, if all of these are effective.

Dr. Joshua Meeks:

And again, these are the sites for PIVOT-006.

Dr. Joshua Meeks:

So, I just want to kind of summarize what I do and kind of how I approach it, and this is really just kind of a beginning of the discussion for what I would anticipate someone with … you know.. If you have intermediate-risk bladder cancer, and you were just diagnosed, this is kind of how that discussion should go. So number one, hopefully you had a TURBT. I usually do a blue light. Hopefully, you got a single dose of chemotherapy, because that decreases the risk of recurrence. I usually meet with people at around a week, and we talk about their pathology and next steps. I talk about what we found, and I usually do give them evidence of like, “This is what your risk score is, you know, zero, one to two, three or greater.” I put this in the notes so it’s clear to my partners, it’s clear to the patient. If someone travels, gets a second opinion, they see all that information. But I think that really begins to have a backbone of like, just based on these factors alone, what’s your chance of this cancer coming back? Um certainly, there’s people who are going to want to do less. There’s some people who are going to want to do more. But I think the key point is if our outcome is recurrence, you know, what do we expect to have happen? I think that just levels the playing field for, you know, where are we, and what do we anticipate this next year is going to look like?

And that’s really where we come up with a plan. The two questions that we need to leave with are, what’s the rate at which we’re going to take a look in your bladder, and then, are we going to do therapy or not? And again, that’s where the risk factors kind of help us make that decision. But again, I have a lot of folks who say, “I just want to do scopes, and if it comes back, I’m willing to escalate it.” I, personally, think that’s totally appropriate um, as long as we kind of know exactly what the risk is. And from there, we just kind of schedule it out. So, I mean, is there anything, Stephanie, that you think I’m doing wrong or that you would say that we should be doing? But this is kind of how much of that, that first visit discussion will go.

Stephanie Chisolm:

Yeah. I think it’s really important, first of all, for patients to just understand their risk levels. So if they don’t know, maybe the next time they go in, they might inquire, they might ask-

Dr. Joshua Meeks:

Absolutely.

Stephanie Chisolm:

“What are my risk factors, and would you classify me as low risk, or intermediate risk, or high risk?” And you know then, you can sort of stimulate a discussion that way by getting it started, by finding out, because I think many patients don’t have that level of detail. This is still a new concept, to have those risk factors kind of scoring you and putting you in a category that now gives you some other options. Because I think many patients don’t have that information, and I’m not sure that as many in the community that aren’t in large academic centers for treatment are getting people to look at that and to share that information. So it would be a good thing for people to ask about.

Dr. Joshua Meeks:

That’s a great point, just to start there. I do find that in general, um, when folks are going to providers that don’t see a lot of patients with bladder cancer, there’s a little too much and a little too … you know .. so we’re probably doing too many scopes, oftentimes, right, too many scopes in low-risk patients, and then maybe offering BCG to low-risk patients which may or may not need it, um and then, when something comes back as like a Stage 1, a T1, and we’re like, “Oh. That’s a high-risk cancer,” maybe not having the discussion about escalating treatment. So you’re right. That so I think from the beginning, to your point, I would say if people could walk away from this intermediate-risk talk with anything, it would be know your risk status. Then, if you are intermediate-risk, maybe start having that discussion about, you know, “Where am I within that, and what do I expect for this year?”

Stephanie Chisolm:

Yeah. Great. Okay. So we did get a couple of questions that came in with the Q&A box.

Dr. Joshua Meeks:

Great.

Stephanie Chisolm:

Is UGN using mitomycin C? Is that what’s in there?

Dr. Joshua Meeks:

Yeah. That’s the chemotherapy. That’s the mito gel, and uh it’s obviously a very special compounding. But the active agent is mitomycin. Yep.

Stephanie Chisolm:

Mm-hmm. Okay. There’s a couple of other questions that might be leaning a little more towards high-grade. Um… When is treatment considered complete? For instance, is treatment considered complete after therapy with BCG, or is it a certain amount of time after therapy and a set number of cystoscopies? This is important when it comes to VA benefits. So let’s take out the BCG, because that wasn’t one of the real things we discussed, but is it considered complete after a certain period of time or number of cystoscopies?

Dr. Joshua Meeks:

Well, so you can do BCG for intermediate risk. Um and it is there as a possibility, and it is effective for patients with intermediate risk. Again, I think a lot of places … like we don’t offer it, because we don’t have as much to offer patients. But certainly, for someone who’s seen chemotherapy, who doesn’t want gemcitabine-docetaxel, BCG as possible. So it actually is reasonable for intermediate risk. Usually, therapy is 12 months for intermediate risk. Uh so you know if you’re going to get chemotherapy, that looks like usually six doses of induction, and then monthly doses of maintenance. For BCG, it’s six doses of induction and then maintenance at three, six, and 12 months.

So it’s usually a year of therapy, and then we stop. And again, to contrast that with high-risk patients, um, ideally, we’re giving three years of therapy for high risk, but again, in our shortage, everybody’s at a year. So you know it’s kinda, it’s brought the ceiling down to the floor, and everyone’s at 12 months. And that, you know, works for a lot of people, but oftentimes, the high-risk patients are much more likely to recur.

Stephanie Chisolm:

There’s another question that was in there, again, talking about BCG and are you all at Northwestern doing a partial dose?

Dr. Joshua Meeks:

Yes. A hundred percent. So um, we’re allotted 39 doses of BCG a month. Um, that’s our allocation downtown. Um … We have four other affiliates across uh Chicago, and some of them actually have more than we do and um … We’ve tried to develop this network where we’re either sending doses, asking them to split and increasing their capacity, or asking people to go you know 12 miles to another facility, but we do split. Um that’s been the guidance from the SUO and the AUA, how to manage that, and you know honestly, we’ve never seen a difference in outcome. I know, again, Ashish has looked at his data.

I would say that the tolerability seems to be just as good, if not better. Um, I rarely think people actually do a little bit better on split-dose BCG, uh and I think the recurrence rates are the same. So I actually think it’s … Not only is it a way to manage the shortage, but I think it’s actually probably a better outcome from a tolerability perspective. Um I do have patients who say they really want full-dose BCG, that’s how the dose is intended, and I say that I just can’t offer them therapy here. So I usually you know refer them out to one of our sites in the city that I know have been giving full-dose BCG, and um you know that’s just what we’d have to do.

Stephanie Chisolm:

Yeah. So um I know back in the beginning of the shortage, we would get calls from patients that said, “My doctor said I have to call the pharmacy to see if they have BCG.” Actually, that, that did happen. I answered a call, and they said, “My doctor said I have to call the pharmacy. I don’t know where to start.” But the question that came in was, “Can patients source BCG on their own through specialty pharmacies?”

Dr. Joshua Meeks:

I’ve never seen that happen, um, where people show up with their own BCG, and we put it in. I don’t know that that’s feasible. Um so I’ve never seen, because it’s a biologic. But I’ve never seen that done. Uh again, in our place, it’s given by our nurse providers, and we get it from the hospital pharmacy. I know we’ve had other sites where it’s given through the infusion centers, um and it’s a little bit different. But I’ve never seen a patient get the drug and show up with it.

Stephanie Chisolm:

Yeah. Okay, and because it comes frozen. You have to defrost it, and yes. It’s distributed not through a specialty pharmacy, but through the entire pharmacy network, through the large suppliers.

Dr. Joshua Meeks:

Yes.

Stephanie Chisolm:

So I did learn something interesting a little while ago in speaking to one of the people at Merck, was that they’re building that second plant, and hopefully the BCG shortage will be over um when that is complete. But what I didn’t know, and this makes a little more sense, was that BCG was first approved by the FDA 40 years ago, and the technology that creates the BCG was 40 years old.

So they’re building a new facility that they must build with 40-year-old technology. So they’re like retrofitting back to that, because if they changed anything, they wouldn’t get FDA approval. So that explains it. Doesn’t make it any better, but it explains why it’s taking so long.

Dr. Joshua Meeks:

Well, and again, I think all of it comes back to how it’s made, right, so the processing. Uh so it came due in bladder cancer in like 1974, were some of the trials. Right? So that’s like fifty-some years. But the vaccine dates back to turn of the century, and the sort of way it’s grown has really not changed. Now, it’s kind of different by strain, and um that’s why I’m optimistic that different strains, combinate strains, strains like you know Tokyo-172, all of these have different ways of being made, may add to that. Right? Because at the end of the day, we just want to be able to give people BCG and give them adequate BCG. Now, we’d love to know if those strains obviously, this is a whole another discussion, but do people have a different response to different strains, and could we, again, give the right person the, the right strain?

Stephanie Chisolm:

Yeah. Other countries have approved um BCG that’s brought in from India and the Tokyo strain, many different strains. Unfortunately, the FDA is still studying whether it’s as effective and as safe for patients. We have time for maybe two more quick questions. What are your thoughts on single agent gemcitabine without docetaxel?

Dr. Joshua Meeks:

Again, I think that is sort of the standard. So when someone shows up with intermediate risk, and we say, “Okay. What would you like to do?” Uh, I always talk to them about a trial. Um but I think the comparison for that is uh single-agent gemcitabine or mitomycin. The two are, you know, never been compared head to head in intermediate risk. Um I-I usually talk to patients about, “Well, let’s start with mitomycin, because it tends to have a little bit more activity.” Um Gemcitabine is actually tolerated probably better right after surgery, but it can cause some nausea.

I have a really high fraction of patients that are women that I care for with intermediate risk, and I will tell you that uh nausea is very common in women with intermediate risk that I treat. I don’t know what that is. Never really been described in a manuscript, but that’s my experience just kind of caring for folks. Women, intermediate-risk, enriched, and then gemcitabine tends to make a little bit of nausea. So I start with mitomycin uh just based on sort of my own experience, but I think they’re both …  And then, I’ll also use docetaxel as another drug to give people.

Stephanie Chisolm:

Mm-hmm. Yeah. That’s interesting. Since it’s intravesically-administered, you would think that nausea wouldn’t be a big deal. That’s fascinating.

Dr. Joshua Meeks:

You know, and It can be real, Stephanie. I mean, I know a patient that uh would be out for like three days after getting gemcitabine, which is just unreal. Right? I mean, you think, that goes back to this, the burden of this, and like you think about one option is we full grade tumors every six months versus being down for three days after therapy when it’s given six weeks in a row. That’s awful. So um it’s just, it’s probably not an acceptable alternative therapy.

Stephanie Chisolm:

Thank you. One last question, and then we have one more question, too. But um is high grade always considered high risk?

Dr. Joshua Meeks:

So it depends on your definition. So in, again, in the US, a small high-grade tumor is considered intermediate risk. Now, in the European system, they would consider high risk, and that patient would get BCG. I kind of have that, again, have that discussion with patients. So if they have a single small high-grade tumor, um, I usually start with chemotherapy, because I’m trying to save the BCG for patients that are multifocal, a Stage 1 with CIS. Um so it really depends on the system and discussion with the patient.

I think, again, the key point is they’re probably going to get scopes every three months for two years, um, and then we’re definitely going to treat them. Again, we’ll have a discussion about, do they want to try chemotherapy or BCG? “Here’s the risk, benefits. What do you think?” Um I would say that the only problem with starting with BCG for patients, again, with like a 3, a small high-grade tumor is that if they don’t respond, they’re BCG-unresponsive, and then you’re sort of in a very different group of folks.

Stephanie Chisolm:

Right. Right. Yeah. Then, you’ve got to escalate, maybe, some of the other options.

Dr. Joshua Meeks:

Right.

Stephanie Chisolm:

Okay. Well, this has been incredibly informative. I’m so excited to have this as a resource for our patients, and I greatly appreciate your expertise and your time.  And you’ve seen so much in the 20 years since you’ve been in the bladder cancer space. So if you could sum it up, what would be one takeaway that you would want patients to know.

Ah. Look at that. You’ve already got it.

Dr. Joshua Meeks:

Yeah. Yeah. No. I think this is it. Right?

Stephanie Chisolm:

Yeah.

Dr. Joshua Meeks:

So, I loved your concept about if you can walk away and at least just know your risk status, like when you walk into your scope, say, “Okay. I’m this,” you know I think that that just begins to empower you to think about, “What should we be doing?” um and so having these discussions with your provider. Right? Again, I think that you know our all is the same is probably changing, and there’s a lot more coming. So, you know this is a very optimistic place. If you’re a patient with an intermediate-risk bladder cancer, I would walk out thinking that the glass is half full, and there’s a lot of good stuff coming… and you know I think the hard thing, again, for the patients that I care for with this is that they’re mostly …  you know they’re looking for a way to treat this with the least amount of toxicity, and I’d say that there’s a lot of people thinking about you and you know I’m very optimistic that we’re going to be there very soon.

Stephanie Chisolm:

Yeah. I always try to remind patients that a clinical trial is a viable treatment option. It gives you an opportunity to use an investigational medicine that’s still being finalized, but you also get much better observation. They’re really watching what’s happening with you with that medicine. So clinical trials are a treatment option, and now, there are so many to, this is…

Dr. Joshua Meeks:

But clearly, you know this space is … I just showed you three groups that … These don’t work without participation of this group. You know?

Stephanie Chisolm:

Yeah.

Dr. Joshua Meeks:

If people aren’t taking an active role to try to make this better, then we don’t get answers, and we can’t say this works and this doesn’t. So um unless communities are bought in to make things better for people, then that’s just not possible and BCAN’s really the responsible party for that.

Stephanie Chisolm:

Yeah. I always say no new treatments happen without clinical trials. So that’s really important.  And again, it’s so exciting. Because of all the clinical trials and all the individuals that really committed to giving their bodies to these new drugs, and trying them out, and working on fine-tuning them, we do expect some of them to get approval in the next six months. That’s really exciting, and obviously, BCAN will announce those things as they come through. Dr. Meeks, thank you so much. This has been a phenomenal resource and a wonderful program.