UGN-102 linked with reduced risk of recurrence, progression, or death in LG-IR NMIBC

In this interview, Sandip M. Prasad, MD, MPhil, discusses the notable findings from the recent Journal of Urology paper, “Treatment of Low-Grade Intermediate-Risk Nonmuscle-Invasive Bladder Cancer with UGN-102 ± Transurethral Resection of Bladder Tumor (TURBT) Compared to TURBT Monotherapy: A Randomized, Controlled, Phase 3 Trial (ATLAS).” Prasad is a urologist with Garden State Urology in Morristown, New Jersey.

Transcription:

What were some of the notable findings? Were any of them surprising to you and your coauthors?

We've sampled from a patient population at higher risk of recurrence. What we found was that for both patient arms, which were randomized 1:1 for treatment, the initial recurrence rates were essentially the same; about two thirds of patients in each arm appeared to have a complete response at 3 months. So again, for TURBT, we know that we're taking patients we resect, but we've selected from a patient group that recurs more often. So it's not surprising in my clinical experience that a proportion of patients are recurring at 3 months. I see that clinically. But I think it's a very novel finding, and something completely new to urologic oncology, that a nonsurgical ablative option inside the body can actually make tumors go away. Now, there have been other studies in the past looking at giving mitomycin with high intensity, meaning multiple times a week. There have been studies looking at mitomycin in different protocols, but these have all been sort of cumbersome or unwieldy where patients are getting many catheterizations, are coming in multiple times a week to get mitomycin, that have shown some degree of efficacy, but nothing that I think is so easy to give. The other really important finding, and I think this bears the merit of the process of treating something across the entire lining of the system, is that when we see patients who have TURBT and the tumors come back, they can often come back in a completely separate location than where the initial tumor was. And the question has always been historically, is this just a new tumor that popped up 3 months later? And I think the truth of it is, it probably is more so that we can't see the tumors when they're really small. We're using our naked eye. We're using a scope that goes in the body. Now, we have some other technologies: narrowband imaging, blue light cystoscopy with Cysview, and all of these are technologies that allow us to improve our ability to do cystoscopy. But overall, the standard approach in the United States and around the world is still traditional white light cystoscopy. Narrowband imaging and blue light cystoscopy require separate purchase of specific instruments that allow for those delivery agents. These are relatively new technologies that have an upfront cost in terms of the hardware of the new scopes. Those new technologies have shown us that we're not perfect at doing white light cystoscopy. When we add in these other options, for better visualization, we actually find additional tumors. That's always been a limitation of traditional white light TURBT, which is what most of us still do. And the reality of the instillation product is the coating is lined completely. The drug is not just injected directly into the tumor base; the drug is given to the entire lining of the urinary system. So in many ways, it doesn't matter if we see it or not. That's really an innovative, novel approach for a disease that we've always assumed has what we call a field defect, meaning there are probably spots all throughout the inner lining that are potentially at risk for disease. And what we're doing is sort of a "whack-a-mole" approach; by the time we can see it, we hit it. And then by the time we see the next one, we hit it. But really, with something like UGN-102 or topical therapies, you don't have to see it to treat it. I think what we see here in terms of the study, is when we look out 6 months, 9 months, 12 months, 15 months later, we can actually see that there's a significant reduction in the risk of recurrence, progression, or death by 55%, with patients who receive UGN-102 up front, vs the patients who just had a TURBT. That's a big number, right? We're reducing recurrence, progression, or death by 55%, because essentially, what we're doing is treating it all up front. You don't have to see it or wait to be able to see it in the future and then address it; you're treating it upfront. My guess is that this treatment option is ablating the tumors that we see, but it's also ablating these microscopic or very small occult tumors that we can't quite visualize yet but we would have seen 3 months or 6 months or 9 months later. So although the upfront data are equivalent, which is still in and of itself, I think really exciting—that you can have almost an equal substitute for resection. Even more interesting to me are the durability data, that you're actually reducing recurrences up front. It makes sense biologically, it makes sense by the instillation technique, and the approach of treating the entirety of the tumor in 1 setting. To me, that was a novel finding that was really important to be able to say that this is a product that, if approved, we should think about as another tool in our toolkit, and maybe even the primary tool in our toolkit, especially for those patients who are older, those patients who are on blood thinners who have to hold their anticoagulation for treatments, those patients who are at anesthesia risk because of cardiopulmonary disease. And for bladder cancer, that's a lot of those patients.

This transcription was edited for clarity.