Management Strategies for Low-Grade Intermediate-Risk Bladder Cancer - Sarah Psutka
May 6, 2025
Zachary Klaassen hosts Sarah Psutka to discuss low-grade, intermediate-risk non-muscle invasive bladder cancer. Dr. Psutka characterizes this as a heterogeneous disease category sitting between low-risk (small, single low-grade Ta) and high-risk disease, primarily consisting of low-grade Ta tumors that can be multifocal or recurrent. While not lethal, she emphasizes it represents a significant burden with approximately 25,000-27,000 new cases annually that accumulate as a prevalent population requiring ongoing management. Historically treated with a cycle of resection, adjuvant therapy, and repeat procedures, this approach creates substantial patient burden. Dr. Psutka highlights emerging clinical trials in two categories: ablative approaches like the ATLAS trial with UGN-102 gel that avoid surgery entirely, and post-resection adjuvant approaches including ABLE-32, PIVOT-006, and MoonRISe-1. She emphasizes the importance of shared decision-making to balance escalation versus de-escalation, focusing on reducing recurrence burden while acknowledging the non-lethal nature of the disease.
Biographies:
Sarah Psutka, MD, MS, Urologic Oncologist, Associate Professor of Urology, Department of Urology, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA
Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor of Surgery/Urology at the Medical College of Georgia at Augusta University, Wellstar MCG, Georgia Cancer Center, Augusta, GA
Biographies:
Sarah Psutka, MD, MS, Urologic Oncologist, Associate Professor of Urology, Department of Urology, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA
Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor of Surgery/Urology at the Medical College of Georgia at Augusta University, Wellstar MCG, Georgia Cancer Center, Augusta, GA
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Risk Stratification for Active Surveillance in Low and Intermediate-Risk Bladder Cancer - Marco Moschini
ABLE-32 Trial Explores Nadofaragene Firadenovec for Intermediate-Risk NMIBC - Neal Shore
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Read the Full Video Transcript
Zachary Klaassen: Hi. My name is Zach Klaassen. I'm a urologic oncologist in Augusta, Georgia. We are at AUA 2025 in Las Vegas. As always, delighted to be joined by Dr. Sarah Psutka, urologic oncologist at the University of Washington. Sarah, thanks so much for your time.
Sarah Psutka: Thank you, Zach, for having me.
Zachary Klaassen: It's always great having you on the set. We always have great discussions, and we're going to have another great one today focusing on this really kind of interesting, complex, and almost barren landscape of low-grade, intermediate-risk, non-muscle invasive bladder cancer. So just tell us-- I know there's a lot of guideline differences. How is this generally defined?
Sarah Psutka: So classically, we think about intermediate risk being-- it really is, as you say, this barren space between the low risk. So a small low-grade TA, single tumor--
Zachary Klaassen: Easy.
Sarah Psutka: --first presentation, and then the high-risk nonmuscle-invasive bladder cancer, which really, I would say, has been spotlighted recently because of the intense interest in terms of trying to develop alternative therapies and sequential therapies to preserve the bladder in those patients. And then everything else kind of fell into this middle ground. And there are some differences in terms of how the different guidelines define this space.
But I think there's kind of growing consensus around the fact that it really does warrant a kind of a careful definition. And even within that, we can-- there's a movement, especially by the IBCG, to start thinking about how we can risk stratify within that group because it's actually a very heterogeneous group.
So just 10,000-foot view-- these are low-grade tumors, small, in general. They can be multifocal. They can be recurrent. They're TA. They're not invasive.
Now, where things get a little bit gray is where do you put the low grade T1s? I will say that's actually something that I think is very rarely seen in true clinical practice.
Zachary Klaassen: I agree with you. I agree with you.
Sarah Psutka: And honestly, if I get a path report that says that, I say, let's look at this a little bit more carefully, because I think oftentimes if there is invasion of the lamina propria, you are starting to move towards more of a high-grade phenotype.
And then where the guideline definitions differ is where do you put the tiny high-grade TAs? The AUA classification system does put that in the intermediate risk group. Although I think that truthfully, once you have high-grade histology, you're starting to talk about a different entity altogether.
Zachary Klaassen: Different biology.
Sarah Psutka: So just to totally summarize. Low grades, TA, multifocal OK, and recurrent OK. And they can recur. And obviously, the big issue here is this is a recurrent disease. This becomes a very problematic chronic illness. And because of that, it's a very high-burden disease. And what's interesting is now, of course, it is becoming actually an area that a lot of people are very interested in.
Zachary Klaassen: How common is low-grade intermediate-risk bladder cancer?
Sarah Psutka: Yeah. So it's actually surprisingly common. If you think about-- so there's about, whatever, 80,000 new diagnoses of bladder cancer-- 75% in the US every year. 75% of those are nonmuscle-invasive. And intermediate-risk disease is probably-- it ends up being somewhere around 25,000 to 27,000 new cases a year. So it's a lot.
And the issue, again, is not that-- those are incident diagnoses. But then those patients remain in that bucket. So the prevalence is actually very high because you're going to have-- these are patients who are-- this is not a lethal disease. And the rate of progression to muscle-invasive disease is actually very, very rare in this group. Progression rates are less than 5%. So you're talking about just an ever-growing category of patients who have a very high burden. Again, chronic illness that requires a lot of intensity in terms of management and surveillance and treatments.
Zachary Klaassen: Sure, absolutely. We're going to get into the clinical trial space in a minute. But historically, how has this been managed over the last 20 years or so?
Sarah Psutka: Yeah. So the classic paradigm is you find a tumor. You resect it. You maybe give-- this is the space for the one dose of post-operative intravesical gemcitabine in the perioperative area, with the goal of reducing recurrence risk. And then a lot of times, these patients will go on to an induction course of intravesical chemo.
But if you think about how frequently the recurrences happen, that means these patients are just being treated over--
Zachary Klaassen: All the time.
Sarah Psutka: --and over and over again. They're in the operating room. Within five years, I think the average number of trips to the OR is about three, which is a lot.
Zachary Klaassen: It's a lot.
Sarah Psutka: Because, of course, you're, again, talking about an older patient population. That's repeated exposures to general anesthesia. Can be much higher than that. You can have-- in some cases, the kinetics of recurrences can be as frequent as within a year multiple times.
Zachary Klaassen: Yeah.
Sarah Psutka: So this is actually this kind of, I would say, very-- there's a lot of debate about how do we handle this space? And there's a tension between escalating care to that kind of classic paradigm-- resect, provide adjuvant therapy, and then rinse and repeat--
Zachary Klaassen: Yeah.
Sarah Psutka: --versus do you resect and observe?
Zachary Klaassen: Yeah.
Sarah Psutka: There's a number-- there's sort of an emerging body of data that sits in this surveillance space, where you actually-- it's more of a watchful waiting approach, or what we would-- active surveillance.
So there's an Italian body of data that supports surveillance for small, less than 5, all less than 1 centimeter low-grade TA tumors and demonstrates the oncologic safety of that approach and the fact that you keep people out of the operating room.
And then there's a lot-- as you said, we'll talk about trials but there's a lot of interest in whether or not we can think about chemo ablation here.
Zachary Klaassen: Yeah.
Sarah Psutka: And can we avoid trips to the operating room--
Zachary Klaassen: Yeah.
Sarah Psutka: --by treating patients in the clinic with something that will essentially treat the tumors without requiring a resection.
Zachary Klaassen: Yeah. Great summary. I think, just to wrap that all up before we move into trials, this is basically a heterogeneity of treatment. And this is why the trials sort of came into vogue in the last couple of years. And so maybe just put a bow on the heterogeneity. There's no real-- there's guidelines, but there's so many options in those guidelines.
Sarah Psutka: Yeah. So I mean-- if you look at the guidelines, the guidelines say that you should resect, and then you can give intravesical chemotherapy or intravesical BCG. And I think that there's definitely-- in the setting of the BCG shortage, trying to give these patients BCG is something that most of us can't do because we don't have drug. And it's being reserved for patients with high-grade, high-risk disease.
Zachary Klaassen: Great point.
Sarah Psutka: So that, I think, is a major just concern we have in terms of resource allocation at this point.
Zachary Klaassen: Almost an escalation that's too much.
Sarah Psutka: Completely. And exposing patients to a therapy that-- I always think about, how many cards can I keep in my pocket for if a patient needs it in the future? I don't want to burn a bridge early. I don't want to expose somebody to BCG if they're going to really need it in the future now.
But then there's the issue-- so that's the high-grade patients. But then-- so I think what most patients get is resect and then induction intravesical chemotherapy. The issue with that is there is toxicity. You eventually run out of lines of chemo. And the definition of insanity is doing the same thing over and over again and expecting a different result.
You've given the patient one line of chemo, and the tumor comes back. You've given them more chemo. And at that point, you're exposing them to a lot of toxicity. You can see tremendous declines in bladder function in these patients who are exposed to multiple rounds of induction chemotherapy.
And then there's all the indirect and financial toxicity of the time in the hospital, the time away from work, the cost of all the therapies. So I think-- and the punchline, the one thing that people need to take home, is this is not lethal cancer.
Zachary Klaassen: Right. Right.
Sarah Psutka: Low-grade TA cancer does not kill people. In very rare circumstances, it progresses. But then you can escalate therapy at that point. Escalating early doesn't help. And so that's where there's a lot of interest in, how can we back off a bit? How can we reduce the risk of recurrence because recurrences are bothersome.
Zachary Klaassen: Yeah.
Sarah Psutka: They are anxiety-provoking. It's tremendously disheartening for a patient to come to you-- I mean, you know.
Zachary Klaassen: Yeah.
Sarah Psutka: The worst thing in the world is you're doing a cysto, and you see another tumor.
Zachary Klaassen: You see a little 1-centimeter. You know it's not going to kill them, but they think the world is ending. Totally.
Sarah Psutka: But it's a devastating moment, and you have to navigate that very carefully. So how can we promote disease-free survival? And so that's where there's a lot of interest in, what else can we do maybe that's a little better tolerated to try to reduce the risk of recurrence because recurrence is the problem in low-grade, intermediate-risk bladder cancer. That's the thing we need to fight against.
Zachary Klaassen: And that's exactly a great lead into this new trial space, which is really exciting-- low-grade intermediate bladder-- intermediate-risk bladder cancer. And, again, you nailed it. And I think that's another great take-home message is this is supposed to be low adverse event. Got to be very well-tolerated because all the things you talked about. So let's talk about some of those trials that are out there.
Sarah Psutka: Yeah. So, like I said, there's two broad categories of trials that exist in this space. So you've got your ablative trials. And that's actually a really interesting kind of emerging space.
Zachary Klaassen: Avoid the OR.
Sarah Psutka: Keep that patient off the table. Do not have that patient-- don't have that patient need to undergo an anesthetic. And this-- I would say the ablative space-- so the first ablative studies that have been done, some of them are randomized controlled trials. Some of them are retrospective or prospective, just observational studies, really were just thinking about can you intensify the exposure with chemotherapy, intravesical chemotherapy?
And there have been a couple of studies where, for example, people got intravesical mitomycin multiple times within a week over a very short condensed period of time. And they demonstrated that the disease-free rates at three months were similar to patients who'd been resected and then looked at again.
So I think the trial that we sort of would want to highlight here, or the trials, would be the ENVISION trial and the ATLAS trial that's using UGN-102. So that's a thermo-ablative-- a chemotherapy containing gel. So this product is placed in the bladder at body temperature. It solidifies. It enhances contact time between the active agent and the urothelium, with the goal of ablating a tumor that has not been resected.
And so the ENVISION trial was a single-arm study. It was stopped early as they moved towards a randomized controlled trial, which was the ATLAS study, which was recently published. And this builds on the upper tract data with the UroGen product. And basically, it's a once a week treatment over six weeks. Primary sort of thing that we're looking at is disease-free-- or complete response, disease-free state at three months.
And let's just take the randomized data because I think that that's probably something that people want to know. If I do this as opposed to doing the classic thing, which is resecting, what's the disease-free rate at three months? And the punch line is at three months the disease-free rate was relatively similar. It was about 2/3-- 64% and 65% in the UGN-102 arm compared to resection.
But at one year, the disease-free rate among those patients who had a complete response rate was higher in the patients who'd been exposed to the drug. And so that's, I think, really interesting.
Zachary Klaassen: And that's the keeping them out of the operating timeline.
Sarah Psutka: And that's keeping them out of the operating room. So if you can extend disease-free control without the requirement of a general anesthetic, that is an incredibly enticing prospect for this patient population.
Now, on the other hand, moving away from ablative trials to more classically, how can we buttress our resection model? So once you resect, what kind of adjuvant therapy can you give that's not chemo, that's not BCG, to reduce the risk of recurrences?
So there's a couple of really interesting new agents. That, in some cases, you're bringing the tools that we have in the high-risk nonmuscle-invasive bladder cancer into an earlier setting.
Zachary Klaassen: Move them earlier, yeah.
Sarah Psutka: So we can talk about ABLE-32, which is looking at using nadofaragene in this setting. Patients who have had resection and then are randomized to either getting nadofaragene firadenovec versus observation.
There is the PIVOT-006 trial, which is using the cretostimogene product. That's another-- an oncolytic adenovirus. You basically turn the cancer cell into a bioreactor that produces more of this therapeutic agent. And that's, again, randomized against observation in patients with low-grade intermediate-risk disease.
And then there's also can we harness biology? So the MoonRISe-1 trial is something that's really interesting. The TAR-210 device is a device that's put into the bladder that elutes erdafitinib, which is an FGFR receptor-- inhibitor. And so this trial is in patients who have tumors that have mutations in FGFR2 and 3. They're randomized to have this device placed.
And the idea is, can we actually-- we know that actually low-grade tumors preferentially have more of these mutations compared to high-grade tumors. Can we leverage that biology to try to reduce recurrence risk? And so I think you've got just a tremendous amount of interest in this space, with the goal of trying to help this patient population who are otherwise really at risk for a lot of toxicity related to the treatment.
Zachary Klaassen: Great summary. I mean, that really highlights exactly where we're at. And it's exciting because a couple years ago, we were talking about all this exciting space in high-risk BCG unresponsive, and that's still going on. But now we're moving all this excitement to the intermediate risk as well.
You had a great take-home message already, talking about reducing the burden of recurrence. Maybe just another quick couple of concluding remarks.
Sarah Psutka: I think it's really important to talk to patients who come in with intermediate-risk disease and to be very clear with them about what the implications of this disease are and what are the goals of care. And then this is definitely a space for shared decision-making around that escalate versus deescalate point.
Zachary Klaassen: Yeah.
Sarah Psutka: And I think it's actually a long conversation. I think people used to think, oh, low-grade -- it's a pretty simple sort of treatment algorithm. We just kind of follow the plan.
But actually, if we're really thinking about what's best for the patient, we need to understand for them what's their priority? Is it staying out of the operating room? Is it really hitting it hard with the kitchen sink, with the goal of hopefully having a CR that's durable?
And then I think understanding a patient's kind of bladder function and their symptom profile is really important because that's going to also inform how much toxicity they're willing to tolerate.
Zachary Klaassen: Absolutely.
Sarah Psutka: So it's nice to have options in this space to talk to patients about and to be able to say, yeah, we can risk adapt here.
Zachary Klaassen: Yeah.
Sarah Psutka: We can intensify, or we can de-intensify. And I think having that conversation around the fact that it's not lethal disease, but what we're really trying to manage is the burden is a really important conversation to drive home because it's a different kind of cancer.
Zachary Klaassen: Yeah, absolutely. Great discussion, as always, Sarah. Thank you so much for educating our listeners again. And we appreciate you talking about low-grade intermediate-risk bladder cancer.
Sarah Psutka: It's a pleasure. Thanks so much, Zach.
Zachary Klaassen: Thanks.
Zachary Klaassen: Hi. My name is Zach Klaassen. I'm a urologic oncologist in Augusta, Georgia. We are at AUA 2025 in Las Vegas. As always, delighted to be joined by Dr. Sarah Psutka, urologic oncologist at the University of Washington. Sarah, thanks so much for your time.
Sarah Psutka: Thank you, Zach, for having me.
Zachary Klaassen: It's always great having you on the set. We always have great discussions, and we're going to have another great one today focusing on this really kind of interesting, complex, and almost barren landscape of low-grade, intermediate-risk, non-muscle invasive bladder cancer. So just tell us-- I know there's a lot of guideline differences. How is this generally defined?
Sarah Psutka: So classically, we think about intermediate risk being-- it really is, as you say, this barren space between the low risk. So a small low-grade TA, single tumor--
Zachary Klaassen: Easy.
Sarah Psutka: --first presentation, and then the high-risk nonmuscle-invasive bladder cancer, which really, I would say, has been spotlighted recently because of the intense interest in terms of trying to develop alternative therapies and sequential therapies to preserve the bladder in those patients. And then everything else kind of fell into this middle ground. And there are some differences in terms of how the different guidelines define this space.
But I think there's kind of growing consensus around the fact that it really does warrant a kind of a careful definition. And even within that, we can-- there's a movement, especially by the IBCG, to start thinking about how we can risk stratify within that group because it's actually a very heterogeneous group.
So just 10,000-foot view-- these are low-grade tumors, small, in general. They can be multifocal. They can be recurrent. They're TA. They're not invasive.
Now, where things get a little bit gray is where do you put the low grade T1s? I will say that's actually something that I think is very rarely seen in true clinical practice.
Zachary Klaassen: I agree with you. I agree with you.
Sarah Psutka: And honestly, if I get a path report that says that, I say, let's look at this a little bit more carefully, because I think oftentimes if there is invasion of the lamina propria, you are starting to move towards more of a high-grade phenotype.
And then where the guideline definitions differ is where do you put the tiny high-grade TAs? The AUA classification system does put that in the intermediate risk group. Although I think that truthfully, once you have high-grade histology, you're starting to talk about a different entity altogether.
Zachary Klaassen: Different biology.
Sarah Psutka: So just to totally summarize. Low grades, TA, multifocal OK, and recurrent OK. And they can recur. And obviously, the big issue here is this is a recurrent disease. This becomes a very problematic chronic illness. And because of that, it's a very high-burden disease. And what's interesting is now, of course, it is becoming actually an area that a lot of people are very interested in.
Zachary Klaassen: How common is low-grade intermediate-risk bladder cancer?
Sarah Psutka: Yeah. So it's actually surprisingly common. If you think about-- so there's about, whatever, 80,000 new diagnoses of bladder cancer-- 75% in the US every year. 75% of those are nonmuscle-invasive. And intermediate-risk disease is probably-- it ends up being somewhere around 25,000 to 27,000 new cases a year. So it's a lot.
And the issue, again, is not that-- those are incident diagnoses. But then those patients remain in that bucket. So the prevalence is actually very high because you're going to have-- these are patients who are-- this is not a lethal disease. And the rate of progression to muscle-invasive disease is actually very, very rare in this group. Progression rates are less than 5%. So you're talking about just an ever-growing category of patients who have a very high burden. Again, chronic illness that requires a lot of intensity in terms of management and surveillance and treatments.
Zachary Klaassen: Sure, absolutely. We're going to get into the clinical trial space in a minute. But historically, how has this been managed over the last 20 years or so?
Sarah Psutka: Yeah. So the classic paradigm is you find a tumor. You resect it. You maybe give-- this is the space for the one dose of post-operative intravesical gemcitabine in the perioperative area, with the goal of reducing recurrence risk. And then a lot of times, these patients will go on to an induction course of intravesical chemo.
But if you think about how frequently the recurrences happen, that means these patients are just being treated over--
Zachary Klaassen: All the time.
Sarah Psutka: --and over and over again. They're in the operating room. Within five years, I think the average number of trips to the OR is about three, which is a lot.
Zachary Klaassen: It's a lot.
Sarah Psutka: Because, of course, you're, again, talking about an older patient population. That's repeated exposures to general anesthesia. Can be much higher than that. You can have-- in some cases, the kinetics of recurrences can be as frequent as within a year multiple times.
Zachary Klaassen: Yeah.
Sarah Psutka: So this is actually this kind of, I would say, very-- there's a lot of debate about how do we handle this space? And there's a tension between escalating care to that kind of classic paradigm-- resect, provide adjuvant therapy, and then rinse and repeat--
Zachary Klaassen: Yeah.
Sarah Psutka: --versus do you resect and observe?
Zachary Klaassen: Yeah.
Sarah Psutka: There's a number-- there's sort of an emerging body of data that sits in this surveillance space, where you actually-- it's more of a watchful waiting approach, or what we would-- active surveillance.
So there's an Italian body of data that supports surveillance for small, less than 5, all less than 1 centimeter low-grade TA tumors and demonstrates the oncologic safety of that approach and the fact that you keep people out of the operating room.
And then there's a lot-- as you said, we'll talk about trials but there's a lot of interest in whether or not we can think about chemo ablation here.
Zachary Klaassen: Yeah.
Sarah Psutka: And can we avoid trips to the operating room--
Zachary Klaassen: Yeah.
Sarah Psutka: --by treating patients in the clinic with something that will essentially treat the tumors without requiring a resection.
Zachary Klaassen: Yeah. Great summary. I think, just to wrap that all up before we move into trials, this is basically a heterogeneity of treatment. And this is why the trials sort of came into vogue in the last couple of years. And so maybe just put a bow on the heterogeneity. There's no real-- there's guidelines, but there's so many options in those guidelines.
Sarah Psutka: Yeah. So I mean-- if you look at the guidelines, the guidelines say that you should resect, and then you can give intravesical chemotherapy or intravesical BCG. And I think that there's definitely-- in the setting of the BCG shortage, trying to give these patients BCG is something that most of us can't do because we don't have drug. And it's being reserved for patients with high-grade, high-risk disease.
Zachary Klaassen: Great point.
Sarah Psutka: So that, I think, is a major just concern we have in terms of resource allocation at this point.
Zachary Klaassen: Almost an escalation that's too much.
Sarah Psutka: Completely. And exposing patients to a therapy that-- I always think about, how many cards can I keep in my pocket for if a patient needs it in the future? I don't want to burn a bridge early. I don't want to expose somebody to BCG if they're going to really need it in the future now.
But then there's the issue-- so that's the high-grade patients. But then-- so I think what most patients get is resect and then induction intravesical chemotherapy. The issue with that is there is toxicity. You eventually run out of lines of chemo. And the definition of insanity is doing the same thing over and over again and expecting a different result.
You've given the patient one line of chemo, and the tumor comes back. You've given them more chemo. And at that point, you're exposing them to a lot of toxicity. You can see tremendous declines in bladder function in these patients who are exposed to multiple rounds of induction chemotherapy.
And then there's all the indirect and financial toxicity of the time in the hospital, the time away from work, the cost of all the therapies. So I think-- and the punchline, the one thing that people need to take home, is this is not lethal cancer.
Zachary Klaassen: Right. Right.
Sarah Psutka: Low-grade TA cancer does not kill people. In very rare circumstances, it progresses. But then you can escalate therapy at that point. Escalating early doesn't help. And so that's where there's a lot of interest in, how can we back off a bit? How can we reduce the risk of recurrence because recurrences are bothersome.
Zachary Klaassen: Yeah.
Sarah Psutka: They are anxiety-provoking. It's tremendously disheartening for a patient to come to you-- I mean, you know.
Zachary Klaassen: Yeah.
Sarah Psutka: The worst thing in the world is you're doing a cysto, and you see another tumor.
Zachary Klaassen: You see a little 1-centimeter. You know it's not going to kill them, but they think the world is ending. Totally.
Sarah Psutka: But it's a devastating moment, and you have to navigate that very carefully. So how can we promote disease-free survival? And so that's where there's a lot of interest in, what else can we do maybe that's a little better tolerated to try to reduce the risk of recurrence because recurrence is the problem in low-grade, intermediate-risk bladder cancer. That's the thing we need to fight against.
Zachary Klaassen: And that's exactly a great lead into this new trial space, which is really exciting-- low-grade intermediate bladder-- intermediate-risk bladder cancer. And, again, you nailed it. And I think that's another great take-home message is this is supposed to be low adverse event. Got to be very well-tolerated because all the things you talked about. So let's talk about some of those trials that are out there.
Sarah Psutka: Yeah. So, like I said, there's two broad categories of trials that exist in this space. So you've got your ablative trials. And that's actually a really interesting kind of emerging space.
Zachary Klaassen: Avoid the OR.
Sarah Psutka: Keep that patient off the table. Do not have that patient-- don't have that patient need to undergo an anesthetic. And this-- I would say the ablative space-- so the first ablative studies that have been done, some of them are randomized controlled trials. Some of them are retrospective or prospective, just observational studies, really were just thinking about can you intensify the exposure with chemotherapy, intravesical chemotherapy?
And there have been a couple of studies where, for example, people got intravesical mitomycin multiple times within a week over a very short condensed period of time. And they demonstrated that the disease-free rates at three months were similar to patients who'd been resected and then looked at again.
So I think the trial that we sort of would want to highlight here, or the trials, would be the ENVISION trial and the ATLAS trial that's using UGN-102. So that's a thermo-ablative-- a chemotherapy containing gel. So this product is placed in the bladder at body temperature. It solidifies. It enhances contact time between the active agent and the urothelium, with the goal of ablating a tumor that has not been resected.
And so the ENVISION trial was a single-arm study. It was stopped early as they moved towards a randomized controlled trial, which was the ATLAS study, which was recently published. And this builds on the upper tract data with the UroGen product. And basically, it's a once a week treatment over six weeks. Primary sort of thing that we're looking at is disease-free-- or complete response, disease-free state at three months.
And let's just take the randomized data because I think that that's probably something that people want to know. If I do this as opposed to doing the classic thing, which is resecting, what's the disease-free rate at three months? And the punch line is at three months the disease-free rate was relatively similar. It was about 2/3-- 64% and 65% in the UGN-102 arm compared to resection.
But at one year, the disease-free rate among those patients who had a complete response rate was higher in the patients who'd been exposed to the drug. And so that's, I think, really interesting.
Zachary Klaassen: And that's the keeping them out of the operating timeline.
Sarah Psutka: And that's keeping them out of the operating room. So if you can extend disease-free control without the requirement of a general anesthetic, that is an incredibly enticing prospect for this patient population.
Now, on the other hand, moving away from ablative trials to more classically, how can we buttress our resection model? So once you resect, what kind of adjuvant therapy can you give that's not chemo, that's not BCG, to reduce the risk of recurrences?
So there's a couple of really interesting new agents. That, in some cases, you're bringing the tools that we have in the high-risk nonmuscle-invasive bladder cancer into an earlier setting.
Zachary Klaassen: Move them earlier, yeah.
Sarah Psutka: So we can talk about ABLE-32, which is looking at using nadofaragene in this setting. Patients who have had resection and then are randomized to either getting nadofaragene firadenovec versus observation.
There is the PIVOT-006 trial, which is using the cretostimogene product. That's another-- an oncolytic adenovirus. You basically turn the cancer cell into a bioreactor that produces more of this therapeutic agent. And that's, again, randomized against observation in patients with low-grade intermediate-risk disease.
And then there's also can we harness biology? So the MoonRISe-1 trial is something that's really interesting. The TAR-210 device is a device that's put into the bladder that elutes erdafitinib, which is an FGFR receptor-- inhibitor. And so this trial is in patients who have tumors that have mutations in FGFR2 and 3. They're randomized to have this device placed.
And the idea is, can we actually-- we know that actually low-grade tumors preferentially have more of these mutations compared to high-grade tumors. Can we leverage that biology to try to reduce recurrence risk? And so I think you've got just a tremendous amount of interest in this space, with the goal of trying to help this patient population who are otherwise really at risk for a lot of toxicity related to the treatment.
Zachary Klaassen: Great summary. I mean, that really highlights exactly where we're at. And it's exciting because a couple years ago, we were talking about all this exciting space in high-risk BCG unresponsive, and that's still going on. But now we're moving all this excitement to the intermediate risk as well.
You had a great take-home message already, talking about reducing the burden of recurrence. Maybe just another quick couple of concluding remarks.
Sarah Psutka: I think it's really important to talk to patients who come in with intermediate-risk disease and to be very clear with them about what the implications of this disease are and what are the goals of care. And then this is definitely a space for shared decision-making around that escalate versus deescalate point.
Zachary Klaassen: Yeah.
Sarah Psutka: And I think it's actually a long conversation. I think people used to think, oh, low-grade -- it's a pretty simple sort of treatment algorithm. We just kind of follow the plan.
But actually, if we're really thinking about what's best for the patient, we need to understand for them what's their priority? Is it staying out of the operating room? Is it really hitting it hard with the kitchen sink, with the goal of hopefully having a CR that's durable?
And then I think understanding a patient's kind of bladder function and their symptom profile is really important because that's going to also inform how much toxicity they're willing to tolerate.
Zachary Klaassen: Absolutely.
Sarah Psutka: So it's nice to have options in this space to talk to patients about and to be able to say, yeah, we can risk adapt here.
Zachary Klaassen: Yeah.
Sarah Psutka: We can intensify, or we can de-intensify. And I think having that conversation around the fact that it's not lethal disease, but what we're really trying to manage is the burden is a really important conversation to drive home because it's a different kind of cancer.
Zachary Klaassen: Yeah, absolutely. Great discussion, as always, Sarah. Thank you so much for educating our listeners again. And we appreciate you talking about low-grade intermediate-risk bladder cancer.
Sarah Psutka: It's a pleasure. Thanks so much, Zach.
Zachary Klaassen: Thanks.