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Zachary Klaassen: Hello, my name is Zach Klaassen. I'm a urologic oncologist at the Georgia Cancer Center in Augusta, Georgia. I'm joined on UroToday by Dr. Sandip Prasad, who is a urologic oncologist in the Atlantic Health System up in Morristown, New Jersey. Sandip, thanks so much for joining us on UroToday.

Sandip Prasad: Hey, Zach, thanks so much for having me.

Zachary Klaassen:  So we're going to discuss GU ASCO data. eUROGEN had some great data there, specifically looking at ENVISION and the impact of multifocality and size of tumors for chemoablation. So maybe just by way of background for our listeners, highlight the overall results that ENVISION has already published.

Sandip Prasad: Sure. So ENVISION was published earlier this year in 2025. It's a single-arm phase III study. 240 patients were enrolled in ENVISION. All patients received the study drug UGN-102, which is a reverse thermal hydrogel. It's essentially the opposite of water.

So if you think about when you put this gel on ice, it becomes a liquid. And then, when it's placed into the body and warmed, it becomes a gel. It allows you to coat the urothelial lining, and it allows contact time for anywhere from four to six, even up to eight hours in certain patients.

This gel can be impregnated with any substance. For UGN-102, the gel is impregnated with mitomycin-- so, again, a substance that you and I use a lot in chemotherapy. The difference, of course, is what we typically give is aqueous, meaning it goes into water and then it's washed out when you void.

This gel is a little different in that it maintains adherence for much longer. And the rationale here is that longer contact time causes a phenomenon called chemoablation. So the really interesting thing about this gel is it's not used in the adjuvant setting like we typically think about chemotherapy-- that is, you do a resection and then you put in the chemotherapy afterwards to try to clean up whatever microscopic disease is left. This is primary treatment. So this actually is competing with TURBT.

So ENVISION had patients who had tumors left into the bladder. As you'll find the majority of these patients actually had multiple tumors left in the bladder. And these tumors were then treated with a once-a-week six weeks of installation of UGN-102.

This is given via traditional urethral catheter. It can be done in the office under local-- a pretty easy process, something we're all really familiar with. And then the primary outcome was investigating the complete response rate for this drug in terms of primary chemoablation.

And so, again, you're seeing here the study design, which are those once a week for six week treatments of UGN-102. And the primary endpoint is that cystoscopy at three months, sort of our traditional look-in, three months after an initial resection. And again, here the important aspect is there's tumor left in the bladder. And so that resection-- that three-month cystoscopy is really to assess for a complete response of chemoablation on the tumor that's there.

So in ENVISION, we found that overall, 79.6% of patients achieved a complete response with primary chemoablation. And these were all patients that had recurrent disease within the past year. That's really important.

So all these patients have low-grade intermediate-risk disease, which is defined as either recurrence, tumors larger than 3 centimeters, or multifocality. So all the ENVISION patients had tumor recurrence within one year. And then we'll talk a bit in this abstract specifically about the other subtypes that are present, which is multifocality versus unifocality and tumors greater than 3 centimeters versus less than 3 centimeters.

But again, for this recurrent patient population, 79.6% had a complete response rate at three months. And then, really importantly, disease assessment was continued with cystoscopy cytology and for-cause biopsy. What we found was that at 12 months after achieving a complete response, the estimated durability of response by Kaplan-Meier's analysis was that 82.3% of patients were estimated to maintain their complete response for up to a year.

And remember, the entire cohort here is defined by recurrence within a year. So these are all patients that recur within a year. And you're seeing a really robust complete response rate of almost 80% and then a Kaplan-Meier-predicted analysis of over 80% of those responders maintain that complete response throughout a year. So that's really exciting data.

But the question becomes, is this low-grade intermediate-risk group-- it's heterogeneous. There's some large tumors, some small tumors, some solitary tumors, some multifocal tumors, and then recurrent tumors all in the mix. And the question becomes, is there a certain subgroup that may not be best for this? Is this sort of highly performing across all the subtypes?

And that's really where this abstract at GU ASCO was presented to really analyze the ENVISION recurrent population, looking at aspects of tumor focality as well as tumor size.

Zachary Klaassen: Yeah, great background. And I think you're right. These are two very important subgroups, looking at multifocality, looking at size. Take us through the key results presented at GU ASCO in San Francisco.

Sandip Prasad: Yeah, so a couple of things I want to point out. So the Figure 2a is looking at the complete response rate in three months. And you can see the first group is separated by tumor count. And here you're seeing that multiple tumors, the response rate at three months is that 79% of these patients had a complete response at three months. So again, even for multiple tumors we're seeing a very robust result.

Not surprisingly, solitary tumors, which is actually a very small subset of the entire population, was 83%-- not surprising, but I'd argue those two numbers are extremely close and very close to that four out of five patient response that we're seeing across the entire cohort. I think it's also important to note that actually, the vast majority of patients, over 80% of patients, had multiple tumors that were chemoablated.

So this is not cherry-picking solitary small tumors, basically multiple tumors, even, with a very robust response. And that's the idea that this treatment is basically treating the field. You don't have to see the tumor to know it's there. You're not injecting this directly into the tumor. Wherever these tumors reside in the lining of the urothelium-- in the dome, lateral walls, posterior walls-- the gel is coating, adhering, and creating chemoablation across multiple tumors.

So I think that's an important facet that the entire study population is fairly enriched with multifocality. And you're seeing among tumor count really a very high and robust difference, between 79% and 83% across the two groups and, again, no statistically significant difference between the two.

In terms of tumor burden, the size point here is 3 centimeters. That's what defines a large or small tumor for intermediate risk. And again, we see that most tumors are smaller. That's not surprising. They're multiple but smaller. Larger tumors comprised about 20% of the cohort. And we saw that the complete response rate there was about 73%. So again, almost three out of four patients with large low-grade papillary tumors still achieved a complete response, which I think is fairly robust.

Smaller tumors, again, you're seeing higher percentages, around 83%-- again, no statistical significance between the two groups, not a surprising finding that you're seeing a more robust, complete response rate for a larger tumor than a smaller tumor. So I want to stop there. We'll talk a bit about durability of response. But I think those complete response data are fairly impressive, really showing that, again, whether it's three out of four or four out of five patients, you're seeing a fairly robust complete response rate across the entire cohort.

Zachary Klaassen: Yeah, I think-- great data. And as I think about from a logistical standpoint-- and I haven't looked at it in the analysis. But in your own experience, maybe, are the dome tumors maybe a little bit more concerning because you got to get the gel across the whole urothelium? Is there any anecdotal experience that they may be harder to chemoablate?

Sandip Prasad: Yeah, so it's a good question. I think, clinically, I don't see that. So again, when we look into these patients' bladders, obviously, dome tumors are sometimes our hardest tumors to get to. And in many ways, it's the tumors that I think patients that I put on these studies, I often do because I think that we're not great at resecting dome tumors really well, which is hard to reach. You're concerned about perforation, et cetera.

It's interesting. I have a patient on a prior study with UGN-102 called ATLAS. This patient was randomized to the gel. This was a randomized controlled trial [INAUDIBLE] between TURBT and the gel. And this patient probably had 50 tumors in his bladder. I think we all have these patients with papillary disease throughout the bladder.

And I was like, oh, boy, I'll put them on study, but I don't know how this thing can work. And actually, that patient-- I may have talked to you about this before. That patient was actually a treatment failure. He had about four remnant tumors out of the 50. And the tumors were actually interestingly posterior wall tumors. They were the easiest ones for me to go back and resect.

And that patient has actually been disease-free since that time. So I always sort of quote that patient because he's actually a failure on study. He is a noncomplete responder. And he's probably my most successful patient who's ever gotten UGN-102 because he's really been disease-free. We sort of changed the paradigm of his urothelial disease.

That's very anecdotal, but that patient, the dome was actually clear. The tumor was actually the opposite of where you'd think it was, right on the posterior wall, and, again, made it really easy to resect. So I'm not sure-- I think it makes sense intuitively if the gel can't get there. But again, the gel solidifies in about two minutes. So with a decompressed bladder, our hope is that with a decompressed bladder we're getting pretty good spread.

There is no pre-existing location that would be ruled out for the study, meaning the tumors could have been anywhere. There was no a priori exclusion for location. So presumably, over 240 patients, you're getting a fair amount of dome tumors that were sampled.

Zachary Klaassen: For sure. No, great answer. Take us through Figure b, looking at recurrence at 15 months.

Sandip Prasad: Yeah, so here we're now looking at all the patients that were complete responders. So this is the durability of response. So think about this as patients 15 months after the initiation of treatment or 12 months after their complete response. We're checking them cystoscopically, for-cause biopsies, and cytologies.

And here the question is, OK, you said that the initial results at three months are pretty robust. How do they do longer-term? And I would argue, again, this is sort of intuitive that you'd see some decline. And this is in terms of recurrence. We're seeing that about 19% of patients with multiple tumors recur.

So over 80% of patients did not recur in that cohort, and then seeing about 12% of solitary tumors recur within a year. And again, you're seeing that 85-plus percent of patients are nonrecurrent in that cohort.

When we look at the p-values for this comparison, there is no difference between the two groups. But intuitively, it makes sense that qualitatively, you're seeing maybe a little higher rate for patients who manifest multifocal disease at the very beginning.

For tumor burden, again, I think it's intuitive. Larger tumors, we're seeing a higher rate-- 20% recurrence rate at 12 months. So again, 80% of patients maintain their complete response 12 months after achieving it. And then for the patients that have smaller tumors, we're seeing about 15%.

So, again, I would say those numbers are fairly close. Clinically, I don't think there's much of a difference when I talk to a patient about, hey, 85% of people did great versus 80% of people. I think those numbers, in my opinion, are equivalent and are both very strong. Statistically, there is no difference between the two groups-- cautioned, of course, that there's some small numbers in some of these groups.

As we start subsetting single tumors, which are a smaller proportion, and large tumors are a smaller proportion, we have some small counts. So I always worry a little bit about statistical analysis with these smaller cohorts. But I think just qualitatively, looking at the numbers, they feel OK to me. They feel like we're getting a pretty robust low recurrence rate across all of these groups.
So importantly, a complete response achieved-- and remember, there's no maintenance in this group. This is durable response from that initial six-week treatment 15 months prior.

Zachary Klaassen: Yeah.

Sandip Prasad: And again, we're seeing that the vast majority of patients can maintain a disease-free bladder during that interval. So again, I think while these results are essentially showing no difference, I think that's the answer. You don't have to overthink intermediate-risk disease.

I think whether it's recurrent, it's multifocal, or it's large, we're seeing pretty good results across the board, really, that the vast majority of patients get a complete response and the vast majority maintain that complete response. I think that's really the narrative that I would send to my patients is that I think we're not really sort of chancing a low yield of results, really kind of with anyone in this intermediate-risk cohort.

Zachary Klaassen: No, that's great. I think you've kind of dovetailed into my next question. I think there's going to be people listening to this that are going to be very excited to use UGN-102 when we get the approval, and they're thinking about which patients use it. And you kind of answered it already, but maybe just restating it, what's the confidence with this additional data that we can use it in pretty much anybody for low-grade intermediate-risk disease?

Sandip Prasad: Yeah, so I think that's the right question. And I'm not sure we answered it until this abstract. I think when you look across the entire cohort, we're clearly taking recurrent patients. And it's very surprising to me that when I talk to patients about ENVISION, most of the urologists I talk to are surprised that over 80% of patients are multifocal.

They sort of assumed that this was going to cherry-pick small solitary recurrences. That's because when we see recurrent bladder cancer, sometimes it's that single recurrence. And they say-- and I agree. Why don't you just fulgurate that small recurrence? Why are you going to go in and give six treatments?

So this is kind of a different type of recurrence. This is multifocal real recurrence in recurrent bladder cancer. These are the nuisance patients for us. These are the difficult patients that have to go through multiple TURBTs, get the blood thinners held, sometimes have bleeding, require a catheter for multiple tumor locations.

I think these are the patients you want to have an alternative for TURBT. The single, small, solitary recurrence, sure, the gel does great, but you could often offer fulguration. I think that's really reasonable. But that's actually not the population of ENVISION. I think that's really important to note.

So again, for me, this is really nice to subdivide this. I was happy that we did these analyses and that we're able to present them is to really demonstrate that this is actually the clinical population that urologists want help with-- multifocal frequent recurrence.
These are the multiple TURBTs. These are the strictures that are developed. These are the blood thinners you got to hold. This is the frustration for patients when they tell them not even is there a recurrence, but there's three or four of them, and we got to go back into the OR and do this. I can't just do this in the office.

So I think that's really an important part of this subanalysis. And I think it also makes it easy for us as the urologists because, remember, this is going to be something that every urologist sees. This is not just for urologic oncologists or fellowship-trained folks. Everyone's taking care of intermediate-risk low-grade disease.

You don't have to overthink the data. You can really offer it to anybody in this cohort and feel pretty confident that you're giving them either whether it's between a 70% to 85% CR and durability of response, those numbers are really easy to remember and just sort of easy to communicate to patients.

Zachary Klaassen: Yeah, fabulous answer. I think my last question is just going to prognosticate over the next, let's say, year or two. Where do we see UGN-102 fitting into the landscape for low-grade intermediate-risk disease?

Maybe outside that a little bit, where is this going? Obviously, we're going to get it, as you said, into the hands of a lot of urologists in the next little bit. But where do you see it really fitting in? We talked about that patient with multiple tumors, the patient we don't want to put to sleep multiple times. Where do you see it in your opinion?

Sandip Prasad: Yeah, so I think it's a great question. Again, the drug is not approved yet. I think they're going there sometime in the summer. So I think, hopefully, we'll begin to hear something about approval potentially in the summertime. So again, this is not quite here, but not too far away in terms of whether we're going to hear about drug approval.

I think you're going to have two schools of thought. One is going to be, well, I still do TURBTs really well, and I'll really just cherry-pick this type of nonsurgical treatment for the ones I don't want to do. And I always just tell urologists, you're still going to do all the cystoscopies. For anyone who recurs, you can always just clean up with the TURBT.

Some of these patients-- we didn't even talk about the fact that there's partial responders. The anecdote I told you about earlier, that's a failure in this study. We don't even count that as something that's successful. But that can be something where that's still a win for the clinical patient.

So I think at the beginning, you're going to have some urologists who really stick to their TURBT regimen and really, again, use this in the patient who's older, sicker, blood thinner, multifocal disease, or the patient where, really, TURBT has been unsuccessful in their hands. I think that's fine.

I think, as we gain more confidence with this, the reality is the implementation is simple-- intravesical weekly installation for six weeks. That's the paradigm in every one of our clinics. So you're just using an agent that's a little different than, let's say, BCG, which probably every urology practice has this paradigm in place with our nurses.

This is a treatment that can be done while you're doing other things. So you can do other TURBTs or cystoscopies or see patients while your nurses are administering primary chemoablation. So this really sort of opens up our practices to more opportunities for growth and for taking care of more patients.

And I think you're obviously going to have some urologists-- and I'm probably in this cohort-- where I would say, why wouldn't you try this first? The vast majority of patients are going to be complete responders. The durability in ATLAS is superior to that of TURBT, again, probably for that field treatment we talked about, that you're treating everything whether you see it or not.
And then, really, only offer TURBT for the small subset of patients that fail. Clearly, cost is going to be an important factor for the utilization of any new treatment. So I think that's going to be a factor for many urologists. But I think, clinically, you can make an argument that says this should be the first-run treatment with really surgical management only as needed for triage afterwards.
And I think you'll find that probably most urologists will start off in the middle. I think that as you gain familiarity, you may not use it in everybody, but you're going to use it in some. As you see success rates that you feel confident about, you're going to be able to expand it.

Zachary Klaassen: Yeah, absolutely. You mentioned confidence. And I think this abstract gives more confidence to folks that are thinking about it, the two important subgroup analyses. Great conversation as always, Sandip. Maybe just a quick takehome message or two for our listeners?

Sandip Prasad: Yeah, so I think primary chemoablation, whether it's with UGN-102, which was the study agent here, or with other agents that are coming up, such as our TAR platforms, this is coming in urology. So we're going to have nonsurgical tools for bladder cancer.

It's going to start off in the safest group to fail in, which is going to be our low-grade patients. It's going to start off in the most bothersome group, which is the intermediate-risk recurrent patients. So most of the studies are in this slice.

But I think it's exciting that we're kind of living in a time where the paradigm for bladder tumor resection, which for decades and decades has been TURBT, we're going to see something new coming. And it's not the sort of 20% or 30% response rates we sometimes see in let's say, for example, BCG-unresponsive non-muscle invasive bladder cancer, where we have to celebrate, kind of, maybe not the majority of patients, but some are going to benefit.

You're going to get the vast majority of patients benefiting probably from any of these platforms. And so while UGN-102 may become the first there, I think we're going to see all of these chemoablative therapies kind of rise the tide across the board, bring more visibility across the entire field for chemoablation. And I bet when we have this conversation five to six years from now, we're going to see that we're talking about a whole different way to manage bladder cancer.

So again, it's going to be coming. And I think your patients are going to want it because they like the idea of not having catheters, not having resections, not having anesthesia, not triaging their blood thinners, not having rebleeding episodes. The safety profile, which we didn't really talk about, from this abstract, is extraordinarily favorable. There were only two patients out of 240 that had a treatment-related adverse event.

One had a stricture. One had retention. They both self-resolved. I mean, this is a really safe approach to managing bladder cancer. So again, I would just tell you whether it's this drug or the next one that's coming, I think get ready for chemoablation. It's really exciting. And I think, for most of us, it's going to be a really nice tool in our tool kit.

Zachary Klaassen: Yeah, no doubt. It's a great time to be treating patients with non-muscle invasive bladder cancer, both for us as urologists who need options and for the patients who are obviously wanting to benefit. So, Sandip, thanks so much. Always great having you on UroToday. Great discussion about the ENVISION subgroups.

Sandip Prasad: Thanks again. Have a great night. Thank you, everybody.

Zachary Klaassen: Thank you.