ENVISION data inform the use of chemoablation in recurrent LG-IR-NMIBC

The FDA approved mitomycin intravesical solution (Zusduri) in June 2025 for adults with recurrent low-grade, intermediate-risk non–muscle invasive bladder cancer (LG-IR-NMIBC),¹ introducing a nonsurgical chemoablation option for this patient population. The approval was based on results from the phase 3 ENVISION trial (NCT05243550), which evaluated the efficacy and safety of mitomycin administered as a reverse thermal gel directly into the bladder.

In the following Q&A, Sandip M. Prasad, MD, MPhil, discusses the trial findings, including initial complete response rates, response durability, and safety considerations, as well as how clinicians can identify patients who may benefit from chemoablation. Prasad also shares his perspective on incorporating this approach into clinical practice, particularly for patients with recurrent disease or elevated risks associated with surgery.

Prasad is the vice chair of urology and director of the genitourinary surgical oncology program at Atlantic Health Morristown Medical Center and Garden State Urology.

Urology Times: What did data from the ENVISION trial show about the efficacy of chemoablation in this setting?

Prasad: We have 2 aspects to efficacy. The first, of course, is the initial complete response. Zusduri is given in the office the same way we give every intravesical therapy. We put a catheter in, drain out the bladder, administer the medicine—which is a mitomycin infused gel—in the office, remove the catheter, and patients can then go home. Patients can drive themselves back and forth for every visit. The treatment cycle is just induction; patients get treatment once a week for 6 weeks.

When we looked back into the bladder with cystoscopy—we also obtained a cytology—we found that 80% of patients had an initial complete response.² What I tell patients is they have a 4 out of 5 chance that when we take a look in the bladder, any tumor that's there will be eradicated. That's a number that patients find to be very reassuring, and I think urologists also find to be high enough that they feel like this is an appropriate substitute for surgery. That's an important and rigorous number.

We're now out to 3 years in follow-up. The follow-up on ENVISION is quite rigorous. For the first 2 years, we did cystoscopy every 3 months to make sure that patients remained clear if they had a complete response initially. [This would be] 8 cystoscopies over the first 2 years, and then at that point we allowed the cystoscopy interval to go to 6 months. That's where we got out to year 3, and that's where all of our patients are at right now. We'll be doing ENVISION follow-up for a total of 5 years, and I think that's important because, as I mentioned initially, the biggest issue with low-grade intermediate-risk non-muscle-invasive bladder cancer is recurrence. If we can show that patients who are complete responders maintain a long-term complete response, that changes the way in which these patients typically behave, which is that we resect them, but they typically recur.

We found that for complete responders, when we followed these patients for 3 more years, and again that's 10 cystoscopies after their complete response, 65% of those patients maintained that complete response for 3 years after their initial treatment.³ Importantly, there was no maintenance on this study, meaning the durable response that patients received 3 years later was due to a treatment they got 3 years prior, with no intervening catheterizations and no intervening treatments. That's very different than what we do in traditional standard of care management where these patients would have received 18 catheterizations for adjuvant gemcitabine or mitomycin. Again, you're talking about de-escalating the number of visits for patients and de-escalating the number of treatments they have to go through. Patients find this to be very reassuring.

Again, [there was an] 80% complete response rate, and for those complete responders, [there was a] 65% chance they’ll maintain that complete response at year 3 after the initial treatment. These are numbers patients understand well. The majority of patients on ENVISION had recurred within the prior year. So, we're changing the natural history of this disease by giving them a field treatment where the gel is covering every surface of the bladder and probably treating those very small microscopic recurrences before they become visible down the road. That's where the magic of these chemoablative treatments work: you don't have to see what you're cutting out like TURBT; you're giving the treatment everywhere and treating even those microscopic or small disease locations that you can't visualize. That's what allows for that durability to be maintained.

Urology Times: Dysuria, hematuria, and urinary tract infection were among the most common adverse events. What should clinicians know when counseling patients about these safety events?

Prasad: You've mentioned the 3 things that we most commonly see with any intravesical therapy. Whether this is from the treatment itself or from 6 catheterizations is unclear, but these are the types of things that I see in all of my intravesical clinics. They're also things that my staff and I are very comfortable helping patients manage because they're so common in our urology practices. [Treatment-related] severe adverse events on the study occurred in only 2 out of 240 patients, and this was urinary retention and urethral stenosis or stricture. Again, this is in a patient population of patients who have already undergone some bladder cancer management in the past. Overall, I think that's quite a low number of patients with some severe event. Both patients resolved their issues, both the stricture and retention.

For the things that we do see at the time of instillation—urinary tract infections, blood in the urine, dysuria—they typically resolve. They're associated with the treatments themselves, but they're not typically long-term changes that we're seeing in patients. Overall, I think [this is] an extremely favorable safety profile and limited because the treatments are limited to the first 6 weeks.

Urology Times: Which patients with recurrent LG-IR-NMIBC may be the most appropriate candidates for chemoablation?

Prasad: Part of your question answered the first aspect: All these patients have to be recurrent. For a patient with a de novo bladder tumor, you're looking because someone had gross hematuria and you see a papillary-looking tumor, that tumor needs to have a TURBT [transurethral resection of the bladder tumor]. You need to make sure that you can adequately establish the grade and stage of any tumor before you begin to put them into a risk category. I always tell patients the first step, no matter what, is full, complete resection with stage and grading.

Following that, intermediate risk is characterized by 3 features, and in post hoc analyses we found that Zusduri works quite well with any of these features. This can be large tumors greater than 3 cm, multiple tumors or multifocal tumors, and tumors that recur within a year. When we looked at the patients in ENVISION, 80% of patients had multifocal tumors and over 50% had a recurrence within a year; there were large tumors in the cohort as well. What we found is that there's efficacy across all 3 of those groups. There's no particular group that you should avoid in this space of recurrent low-grade, intermediate-risk non–muscle invasive bladder cancer.

I start off with a certain type of patient initially, and it's the patient [for whom] I don't think the current strategy is working. This may be a patient who's recurring every 3, 6, or even 12 months, and has done this for several years. Clearly, my existing strategy of TURBT or intravesical therapy isn't effective in that patient because they keep recurring, so for me it's a nice way to pivot to something novel that appears to have quite a bit of efficacy and durability. The second type of patient is the one who has complications from going through TURBT. These are patients who are on blood thinners chronically, and it's a risk for them to come off it because they have a valve, or they have a history of stroke or blood clots. It's patients who have anesthesia complications, so people with heart attacks or COPD [chronic obstructive pulmonary disease], where putting those patients to sleep can have some sort of adverse event on them as well. That's an easy second patient for me to pick to start a nonoperative approach because I can keep them out of the operating room.

But again, in the end, fortunately, because the efficacy data [are] so strong, there really isn't a patient population that you should not use Zusduri. I tell most providers, use Zusduri initially in those patients you don't want to operate on. I think most of us know who those patients are in our practices. Once you start there, you build confidence and comfort. Now that the drug has been on the market for over a year, I think that providers are beginning to expand the use of Zusduri across the entirety of the space, and that's how I use it as well. But I think, again, patients who either have operative risk or those patients who have recurrent disease despite what we're doing currently, those are no-brainers in my opinion.

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REFERENCES

1. FDA approves mitomycin intravesical solution for recurrent low-grade intermediate-risk non-muscle invasive bladder cancer. News release. US Food & Drug Administration. June 12, 2025. Accessed October 12, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-mitomycin-intravesical-solution-recurrent-low-grade-intermediate-risk-non-muscle

2. Prasad SM, Shishkov D, Mihaylov NV, et al. Primary chemoablation of recurrent low-grade intermediate-risk nonmuscle-invasive bladder cancer With UGN-102: A single-arm, open-label, phase 3 trial (ENVISION). J Urol. 2025;213(2):205-216. doi:10.1097/JU.0000000000004296

3. ZUSDURI median duration of response still not reached with 64.5% 36-month duration of response in the pivotal ENVISION trial. News release. UroGen Pharma. May 13, 2026. Accessed October 12, 2026. https://investors.urogen.com/news-releases/news-release-details/zusduri-median-duration-response-still-not-reached-645-36-month/