Alan Wein: Hello again, it's Alan Wein from the Functional Urology side of UroToday. We have the honor of having Sean Elliott, a professor of Urology at the University of Minnesota, talking to us about one of the many subjects in lower urinary tract dysfunction, this one a structural one that he's an expert in, and that is the use of a new technology basically for treating urethral stricture disease. He's going to talk to us about how to use it, what the results have been, who to use it in, and who not to use it in. Sean, thank you so much for being with us and take it away.

Sean Elliott: Thank you, Alan, for that nice introduction. Optilume is the trade name for the paclitaxel drug-coated balloon marketed by Laborie and I was the principal investigator of the phase one and three studies on the Optilume balloon for urethral strictures. I'm going to cover a slide deck here that introduces you to Optilume for said disease.

One question I do get a lot is how to code the Optilume, and that is that you can bill a direct vision internal urethrotomy with Optilume at the same time. They're not bundled together. People often will want to first open up the stricture with either an internal urethrotomy or a balloon dilation before applying the Optilume balloon. That answers this question about can I bill a DVIU as well?

The indications for the Optilume drug-coated balloon really boil down to the length of the stricture, the location, the etiology, the age of the patient. These are all the factors that come into mind when we're thinking about whether to use Optilume for a particular patient who has urethral stricture disease. I'm going to review for you the data we have from the randomized trial and then come back to some of these particular indications in brief.

What we know from the randomized trial is that there is good improvement in IPSS with application of the Optilume drug-coated balloon for short bulbar urethral strictures. That is that in the randomized trial, almost all the patients had strictures that were about one and a half centimeters. They had to be less than three centimeters to be in the trial. Almost all of them were bulbar and almost all of them had not had radiation. So with those caveats, we know that the IPSS improves in both the control arm patients and the Optilume arm patients, but then in the control arm, the IPSS quickly rebounds to being poor and we see a durable improvement in the IPSS out to now four years with Optilume.

Alan Wein: The control arm with what, Sean? Is that just the balloon without the medication?

Sean Elliott: Yeah, thank you. Ideally, it would've been the exact same size balloon but without medication, but the company wanted to open it up to usual care, and so they also allowed people to have a DVIU, to have dilation with serial dilators like urethral sounds. About 50 or 60% of the people had a dilation in the control arm with a uncoated balloon, and then the remainder are with those other two methods. The Qmax also has some durable improvement, but I'll point out that over time the Qmax is declining I think a bit faster than the IPSS.

When we look at the outcome of freedom from repeat intervention, the control arm had a 80% retreatment rate within one year. I will point out that they were unblinded to their treatment after six months, and so it's possible that some of these men sought retreatment after six months because they realized they had been randomized to control, but you also see a very high retreatment rate in those first six months in which they had remained blinded. Then the Optilume patients have a freedom from repeat intervention of 68.5% at four years.

This summarizes all the Optilume studies for urethral stricture out there to date. In general, we see about a 50% reduction in the IPSS and about a 15-point improvement in the Qmax, summarized down at the bottom here, and about a 75% freedom from repeat surgery across these studies, but almost all of them have follow-up of one year or less. So we're really looking forward to some longer-term data.

Importantly, what kind of men were excluded from this ROBUST III trial? Posterior urethral strictures, that is people with prostatic strictures. Penile urethral strictures were not included, but only 10 of them were in the study. Longer strictures were excluded. People who had had less than two previous endoscopic treatments, so we can't really make a comment on the role of Optilume for a treatment-naive patient or someone who's only had one prior dilation. People with hypospadias strictures, people with lichen sclerosis were excluded, and people with previous urethroplasty. Then people with prior radiation were not excluded, but again, there were only about 12 men with radiation in the study.

This is the forest plot of the outcomes, and based on the inclusion criteria, we can say that the data is really strongest for men with short urethral strictures and we can say that, whether their stricture is greater than two centimeters or less than two centimeters, the Optilume performed equally well, and whether they'd had less than five prior treatments or greater than five prior treatments, it performed equally well. It's harder to make comments on the radiation strictures and the anatomic location strictures because so few of those people did have penile urethral strictures.

So in summary, I would say that when evaluating a man with a urethral stricture and you're considering whether to do Optilume, think about some of these variables. If the urethral stricture is less than or equal to three centimeters in length, they're an excellent candidate. If it's in the bulbar urethra, we know it works well there. We know less about the posterior urethra and the penile urethra.

In terms of prior treatments, we know it works better than control in people who've had multiple prior treatments. It's harder to say if it works better than control in the treatment naive person. In terms of etiology, if they've had prior hypospadias repair or lichen sclerosis, we don't know if it works better than control and we don't know if there would be more complications with Optilume. People with lichen sclerosis or prior hypospadias repair are very fragile urethras, maybe there's some toxicity from the Optilume, the paclitaxel that we are not aware of in those patients.

We don't know how well it works in female urethral stricture and we don't know the role of Optilume in younger patients versus older patients. I frequently get a young guy, and when I explain the success rates, they often opt for something with more durable success like a urethroplasty. Then radiation strictures, we don't know the success rate of Optilume for radiation strictures, but those are also very difficult things to repair with urethroplasty, so there's a good opportunity in that patient subset. Then similarly, prior urethroplasty, once you've had one urethroplasty, it's more difficult to do a second one. So if we can demonstrate good outcomes with Optilume in that group, that would be a win.

Alan Wein: So how exactly do you do this? The balloon comes deflated, right?

Sean Elliott: Yeah, so the Optilume comes in a package. It is a drug-coated balloon, it is deflated. It is a low pressure balloon. So if you compare that to something like the Uromax that we use to do PCNLs and lots of people use to do urethral stricture dilation, those balloons can achieve a high PSI. This, it achieves about half the pressure of those balloons. You don't want to go above 12 atmospheres with this balloon, whereas those go up to 20. A lot of people do like to do a pretreatment of the stricture because they're afraid that the 12 atmosphere balloon may not be good enough for cracking open the stricture. So you'll do a DVIU first or use a high-pressure balloon first, get it open, and then use the Optilume more like a drug delivery device than a therapeutic dilation. Other people will look at the stricture and say, "This looks like a soft stricture. I'm just going to deploy the Optilume right away and reserve pretreatment for people with really dense strictures."

Alan Wein: Do you tell patients upfront what the likelihood of retreatment is, and what exactly do you tell them?

Sean Elliott: Of course, yeah. I tell them that there's about a one in three chance that within a year your stricture will narrow back down such that I can detect it on cystoscopy. About on three times it will look narrower than 20 French on cystoscopy. But when we follow those people long-term, most of them remain happy. If we follow you out to four to five years, your AUA symptom score has a two out of three chance of still being in the happy range. Then in terms of what to do if it does fail, do offer people retreatment with Optilume, if that's what they want to do. Oftentimes people with very complicated strictures, like radiation strictures, will opt for that and they'll consider it a success if let's say beforehand their urologist was dilating them every three months for a very recalcitrant radiation stricture and then with the Optilume, maybe they only need to get retreated once every year or two. That's a failure because they had to be retreated, but in their minds it's a win.

Alan Wein: So how long do you leave the catheter in, or do you?

Sean Elliott: We leave the balloon inflated for five minutes and I leave a catheter in for three days.

Alan Wein: Right. Same catheter, you deflate the balloon, or put another one in?

Sean Elliott: The balloon comes on a tiny little three or five French-

Alan Wein: Right, so you put in afterwards?

Sean Elliott: ...and so we put a standard Foley catheter in afterwards.

Alan Wein: And you put the balloon catheter in under fluoroscopy?

Sean Elliott: Yeah, you can do it under fluoroscopy, you can do it under cysto or some combination of both.

Alan Wein: So it sounds like overall, I mean, you've been very happy with this treatment, whether it's long-term or whether people have to do this over. It apparently works as well if you have to do it over again. Let's say they symptomatically stenosis, and yeah, okay, the stricture came back, we're going to do it again, the likelihood of success is really the same?

Sean Elliott: That we don't know. We don't know the likelihood of success in retreated people, people who've gotten more than one Optilume. But anecdotally, if they've failed one Optilume, they're probably going to fail again, but some people will opt to go that route anyway because happy with getting one or two years of success.

Alan Wein: Yep, I think less invasive is the key, even if it means more treatments. Well, listen, thank you so much. I mean, that was really informative. I'm sure that everyone who watches this will know more about this now, because it was a little bit of a mystery to me and I think probably to the rest of people who watch this UroToday series. But thanks so much because I think it's really going to be a big help in treating the urethral stricture population, even as you say, in the bad ones if it prolongs the duration between the times that they have to come to the office to be dilated or something like that.

Sean Elliott: Well, thank you for letting me share some of my thoughts and shed some light on it.

Alan Wein: Yeah. Listen, thank you so much.

Sean Elliott: Bye-bye now.