Alicia Morgans: Hi, I'm so excited to be at AUA 2022 with Dr. Kyle Rose, who is at Moffitt Cancer Center. Thank you so much for being here with me today.

Kyle Rose: Thank you for having me, Dr. Morgans.

Alicia Morgans: Wonderful. Well, thank you, Dr. Rose. I wanted to just speak with you a little bit about an analysis that you and your team have done. It's very exciting. Looking at mitomycin gel for upper tract urothelial carcinoma, following the recent approval, and really looking at this in a real world setting. Can you tell me a little bit about why you needed to do this trial in the real world setting and also, how did you find the data? What data set did you use?

Kyle Rose: Yeah, all great questions. So the recent approval of mitomycin gel for the treatment of low grade upper tract urothelial carcinoma happened in 2020. That was all based on the OLYMPUS Trial. And there are significant side effect profile and safety issues that I think community urologists have shown some issue with. And we really evaluated, is there a new method of drug administration that could lead to lower side effect profile and better safety?

Alicia Morgans: Wonderful. So what are some of the safety issues that you normally are thinking about with this particular agent?

Kyle Rose: I think the one that most people know is the high rate of ureteral stenosis, that scar tissue in the ureter, which can eventually block the kidney and cause renal failure. The rate of stenosis in the Olympus Trial, which is the trial that led to approval of the drug, was about 44%. And so there's definitely a stenosis rate that could be improved upon. And I should mention, I'm sorry, the authors of the paper of the trial, had hypothesized that the stenosis rate was because of repeated instrumentation of the upper tract. And that is sort of what drove us to this next step of, is there a way we can deliver this agent without repeated instrumentation?

Alicia Morgans: Absolutely. And very important for patients because that's a relatively higher rate than we would wish. So tell me, what data set did you use to really evaluate this in a real world setting?

Kyle Rose: Great question. And its sort of a weird story. I was very fortunate to train at Mayo Clinic in Arizona with Dr. Mitch Humphreys. And now I train at Moffitt Cancer Center with Dr. Wade Sexton and both used the gel mito or the mitomycin gel in the anti integrated setting through a percutaneous nephrostomy tube. And so we didn't necessarily have a data set. I knew two high volume institutions, and then we sort of reached out to other institutions that we knew were doing this from an integrated route.

Alicia Morgans: That's actually wonderful though, because you couldn't get more real world, I think, then putting together a bunch of groups that are doing this in a high volume type of a way. And as you designed it, what were you looking for and what did you find?

Kyle Rose: So we were looking at the safety profile, that was our primary outcome. I think in order to look at oncologic outcomes, you really need long-term data. And because of the novelty of the drug and the administrative technique, I don't think that data would be present for us to feasibly make any real oncologic conclusions. So our primary outcomes were really safety data, and what really caught our attention was that rate of stenosis after induction therapy.

Alicia Morgans: And what did you find?

Kyle Rose: So our stenosis rate, and it's important to say how we defined it, because it really comes down to how you defined ureteral stenosis. We define it as any sort of constriction, either on direct vision or pyelogram, that then requires a discrete dilation. So, any scar tissue in which you have to act upon, and whether that's a dilation or a stent placement. And using that very strict criteria, we only had three cases and our stenosis rate was 9% in our series.

Alicia Morgans: Wow, well, that's actually very encouraging in a real world data set where perhaps the patients may be more frail than those patients included in a clinical trial or have comorbidities that wouldn't allow them onto a clinical trial, but you're seeing them in the real world, so that's really encouraging.

Kyle Rose:We are. We also have to keep in mind that because it's retrospective, we're not constantly prompting patients and assessing patients. This is all based on patient reported symptoms. So there's always going to be a bias there, but you're right, that this is clinical practice based and real world based.

Alicia Morgans: Wonderful. So tell me, what are you and the team doing with this information? How does this affect your clinical practice?

Kyle Rose: I think it offers another way to administer this drug for patients that are poor operating room candidates, for patients who are not good candidates to go under general anesthesia repeatedly. And from a hospital resource management standpoint, it helps keep us out of the OR and out of the endoscopy suites, because we can administer it in clinic.

Alicia Morgans: That's also really, really important, especially in these days where COVID has affected operating room availability and it probably will continue to over time, in various places in various ways. So what would your message be to listeners as you have an overarching theme, I would imagine, for the real world study that you've done?

Kyle Rose: I think that we've shown in our series, that this is a safe route of drug administration. Further studies are absolutely needed hopefully in a prospective manner. So we can look at patient discomfort outcomes, to ensure that the discomfort of a percutaneous nephrostomy tube does not outweigh the benefits of avoiding the operating room and repeated instrumentation. The low rates of ureteral stenosis are very encouraging, but we also need long term follow up to confirm that the oncologic efficacy is preserved.

Alicia Morgans: Absolutely. Well, I look forward to continuing to have discussions with you and hopefully hearing about some of that data over time.

Kyle Rose:All right.

Alicia Morgans:  Thank you for your time.

Kyle Rose: Yeah. Thank you, Dr. Morgans.