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Diane Newman: Welcome to UroToday's Bladder Health Center of Excellence. I'm Diane Newman, the center's editor, and I have with me a colleague that I'm very excited to present to you. His name is Dr. Steve Kaplan. He's a professor of urology at Icahn School of Medicine at Mount Sinai. He's also chair of research at the American Urological Association, Director of the Men's Health Program at Mount Sinai Health System, and today he's going to talk to us about his presentation that he did at the AUA on the Optilume device for men. Welcome, Steve.

Steven Kaplan: Thank you very much for inviting me. Diane. It's always good to go with folks like you who know so much about the field. This is kind of the first time that's being presented in the United States. We did that at the AUA. This is a new technology that has been improved in the past for urethral stricture, but this is for BPH and I have the privilege of being the principal investigator and sharing these results.

And BPH is kind of evolving and it evolves and sometimes I feel like I'm in the movie "Back to the Future" because things like balloon dilation and urethral stents are now coming back and this is the data here on using a balloon, a balloon expander. And what's interesting is that this is the first BPH device that will use both a drug as well as a device itself.

So it's the first combination as opposed to either a drug alone or a minimally invasive device. And the concept is to use this balloon, which is not your grandpa's balloon, BPH balloon like in the nineties that actually performed what we term is what we call an anterior commissurotomy, which essentially means is that we really split the anterior part of the prostate open.

And what's nice about it is that, that we think is why there's a maintenance of results and more specifically as I'll talk about in a few minutes, maintenance of the objective results. So the way I like to describe it is the old balloon dilators took a channel and expanded the O, made the orifice larger. And what this does is actually create a V because basically you split the anterior commissurotomy and the idea is one of the best procedures for BPH is an open prostatectomy. And the way we start doing that is to actually do an anterior commissurotomy so that's why we think it kind of makes sense to us. It made sense to us.

In addition, this balloon is drug-coated, so it has paclitaxel which has been used in a lot of different situations, certainly also in various types of blood vessels. And the paclitaxel we believe decreases the inflammatory response and therefore keeps the, and maintains if you will, the effect. So this was a typical BPH study, and the inclusion criteria are pretty standard. Exclusion criteria are pretty standard as well. And this was a sham-controlled study because to get FDA approval for a BPH device, you have to demonstrate differences between the treatment group and the sham group.

These were the two, at baseline, the two treatment groups, typical classic type of study. Prostate volume was 45 grams or so in both groups and we excluded patients over 80 grams in this initial study. But you could see this a typical type of patients with significant symptoms and severe symptoms and impaired flow rates.

This was the follow-up essentially was a year long study and the Optilume group had 98 patients at the get-go and this was a two to one randomization. And interestingly enough, 20 subjects in the sham opted to go over to the Optilume BPH. So like any typical sham study, you do it for three months and the patients have the option to going over to the Optilume group.

So this was the improvement in symptoms over time. And obviously we look at the one year and there was clearly a significant improvement in the treatment arm, statistically significant compared to the sham arm. Now what's interesting is a couple things. One is that the effect is maintained. Now if you look at the three month, you look and see that there's significant improvement in the sham arm as well.

Of note, this is the first study where 100% of people in the sham arm thought that they were being treated and we've never seen that before. Usually it's about 50%, but it's the first time that a hundred percent of people in the sham arm thought they were being treated, so we were very happy that actually the study in terms of the randomization and protecting the blind was actually there. But ultimately you could see that at a year there's significant improvement with the treatment arm.

And this treatment level of improvement compared to sham is pretty consistent with what we seen with some of the other minimally in devices like water dilation with the resume device and prostatic urethral lift. Now another metric we use is the minimum clinically important difference, which can be defined as either a, and we followed the FDA guidance of a 30% improvement.

And at all points you can see that the treatment arm had that level of improvement and was sort of pretty happy with the fact that even from the get-go it had it, but certainly at 12 months this effect is actually maintained and what would argue actually improved, while you can see a diminution of the effect and the sham arm at a year, but this is kind of the most important slide. That is the improvement in flow. We have never seen an improvement in flow, peak urinary flow rate with a minimally invasive device like this.

It's almost 10 mLs per second and it's an 113% improvement at one year. And this approaches what we see with surgery. So this is significantly better than anything we've seen with minimally invasive devices before. And although I'm not going to present it today, in another study that I presented at the AUA, the phase two study which we termed the EVEREST study, we see this at four years as well.

So this is not a one-off observation. Every study we've done with the Optilume BPH balloon demonstrates a peak flow rate of almost 10 mLs per second. This is what we see with the TUR Greenlight laser ablation, et cetera. So this to me is the difference maker with potentially with this device. So you can see the improvement initially and the improvement over time. So one would argue that not only does it happen right away, that effect is maintained as well.

Post void residuals also significantly improved and that effect is maintained as well. So this hits all the things that we like to see. It improves symptoms, it improves peak flow rate, it improves PVR, but it's virtually historic improvements in peak flow rate and that's as a percentage that's maintained over time.

Sexual function is maintained and specifically erectile function as well as ejaculation. Approximately 4% of patients reported changes in their ejaculation. 96% of patients said there was absolutely no change.

So in conclusion, this was a good study. We were very proud of the fact and I congratulate my co-investigators on the study. It was well executed. The bottom line is that when you see such an overwhelming amount of people who thought that the sham arm, that they were getting treated the study was good, the effects are maintained. And I think that the real difference in this technology is that the peak flow improvement was maintained for such a long period of time.

Obviously we're going to follow up these patients over time. This is not yet an FDA approved device. It's under regulatory review. This will be published by the way, this study in the Journal of Urology was accepted, so it'll be hopefully in September I think it's going to be published and more than happy to share more of the specifics. So thanks, Diane, for giving me the opportunity to present this.

Diane Newman: Yeah, thanks so much. Tell me a little bit about the shams. So that was interesting that a hundred percent thought that they actually had the treatment. What did you do for the sham?

Steven Kaplan: Just cystoscopy.

Diane Newman: That's all. Just cystoscopy?

Steven Kaplan: Yeah. And it's actually kind of interesting because we created this background noise or lack of noise as the case may be so it's kind of interesting how patients actually thought that they were getting treated.

Diane Newman: But you are right. In shams you never see a hundred percent, so that was really interesting that you saw that.

Steven Kaplan: Amazing. It was amazing to us, which actually helped. It's nice to know that the study was well conducted and other studies are well conducted too, but this was really well conducted, so we're pretty confident that the results are real.

Diane Newman: Now you've mentioned sexual activity afterwards and how the outcomes from that. What about urinary though? Because we know a lot of times we touch the prostate of course that's kind of where I do a lot of work in practice is there's urinary symptoms and a lot of these men have urgency frequency beforehand due to hyperplasia of the bladder, whatever. But what happened afterwards with their symptoms as far as urgency, frequency or do they develop incontinence?

Steven Kaplan: So no incontinence and over time their IPSS both in the storage and the voiding phase is improved. Like everybody else some patients initially will always complain of some urgency for the first couple of weeks, but in terms of overall symptoms, there was an improvement in both of them and pretty significant. Significant.

Diane Newman: Yeah, that's what I think was exciting because of course with anytime we touch the prostate, we tend to see maybe some urinary symptoms. Now how long is the procedure though? How long? Is it long? How much longer than a cystoscopy?

Steven Kaplan: It probably takes overall about 15 minutes from wheels up to wheels down obviously depends on the anesthetic. Most of the patients here had general anesthesia, but for example, the room study where I think about two thirds of patients had general anesthesia, in the real world, most of these and we anticipate will be an office procedure. It can be done obviously in a hospital setting or an ABC setting, but we anticipate that with local prostate block will be able to be done in the office.

Pretty similar mean we used to do microwave and TUNA in the office with prostate, so I presume we'll be able to do the same thing with Optilume as well, interestingly enough that the pain was even less when you used localized anesthetic on the prostate block because we did the pain scores, so it can be done and I think we anticipate that this will be an office procedure.

Diane Newman: And what do you think though, that over time, do you think these results will really persist? Do you think that this is something maybe in, I don't know, five years they'll have to have it again? What do you-

Steven Kaplan: Well, five years, I don't know. I think clearly what we've seen at least at four years, I think there was one patient retreated not in the PINNACLE study, in the EVEREST study. So it seems to have some good durability. But the retreatment rates in clinical studies is always going to be lower than what we see in the real world. And we've seen that.

We've actually presented or about to publish some data about retreatment rates for Rezum and UroLift and TURP and Greenlight are much higher than what we've seen in the clinical studies. And the difference is when you do a clinical study for a regulatory study, it's only those patients who are followed up that get included. The patients who are lost to follow up, they're gone. So we don't know what happened to them. In the real world, it's the real world, everybody in, everybody out.

So that's the real retreatment. And so we've seen much higher retreatment rates in real world data, not just our own, but in various studies that demonstrated that. So what it will be with Optilume, I'm not really sure yet. It's been very low, lower than what we've seen with others.

But let's just say for example, it's 5% at five years, 10% at five years. Given the fact that, A, they don't have to take a pill every day. And I was one of the people who was involved with virtually every clinical medical study, alpha blockers, five ARIs and I was a big proponent of medical therapy. But as I've gotten to that age, unfortunately I'm not on any BPH medications, at least not yet. Do I want to be taking a pill? Do I want to be prescribing a pill to a man in their fifties to be taking for 20 years or 30 years? Does that really make sense?

And I think patients would tolerate another treatment as long as it's pretty easily done. Look, patients take Botox in their bladder every three months or six months and get a cystoscopic procedure to do that. I think the key thing is to manage expectations and I think that's why we really need to define re-treatment better and patients will accept that as long as we give them the right data.

If you tell them, well it's going to last for 10, 15 years, that's not going to happen. But 5%, 10%, whatever that retreatment rate's going to be at five years, that's going to be fine as long as we kind of know those numbers. And I think that's really what our goal is to do. And I think now that there's emerging data with some long-term side effects with medical therapy for BPH, for example, the five ARIs, this emerging data with dementia, depression.

And this is not one study and this is not a small studies, this has been published in JAMA, but these are real studies. You got to be careful. And it's not that we shouldn't use medical therapy, but I think the notion of doing a minimally invasive type of therapy or a surgical therapy is going to get more appeal, particularly if we don't want to be on these therapies for a long period of time.

Diane Newman: Yeah, Steve, just this week I looked at your LinkedIn page where you talk about the study with dementia, with the medication. I know that was really astounding to me. I mean, you're right. Long term these medications are good, but we look at what's happening in this age group as they age, what other effects are we seeing from some of the medications we're prescribing.

And also, you did look at sexual function. We do see sexual side effects of the oral medications, which a lot of patients complain about. So there actually is a lot of benefit. Tell me a little bit about, I know you have a men's health center in New York. Tell me a little bit about it. So you're treating just men and I guess all the different therapies. What besides BPH are you treating?

Steven Kaplan: Well, sexual dysfunction, testosterone, and we have a bunch of folks under our umbrella who I'm not going to do penal prosthetics. And there are other groups, there are other people in the group who will do the injections or the shockwave ESWL testosterone type of management. I think one of the things we're looking to do, and it's interesting because I think technology will help us, is to try to get people earlier into the system and not so much coming to the hospital, but to try to prevent them from needing to get medical care.

And I think the term that I'm going to be using a lot and I use a lot with patients is I want to convert them from instead of a health insurance to health assurance. And rather than wait until somebody is sick needs to start using their insurance to pay for it, I'd rather try to get people to assure their health that they won't need to come in.

And I think with the notion of remote diagnostics, which is going to be very, very big people are wearing, here, I have my own walking around diagnostic elements and I think developing that for urology as well, that people will hopefully act sooner preventively, which includes good diet and exercise and reinforcing that type of behavior. And I think we're just beginning to touch upon what technology can do and will do to I think at least be able to communicate that information.

We were involved with some entrepreneurial activity and some startups that are actually focusing on that in various types of groups. So that's where I'd like to see it go as opposed to just having people come in and being taken care of after they have a problem. And I think the notion of being able to interact with patients remotely, clearly with Covid, we realized we can do a lot of that and patients like that.

So I think that's really where the future's going to be and we're trying to evolve into that system and evolve into that. That will take time. And I think future generations should be focusing on that piece of it to take better care. It's not just with BPH. That's true for other disease types and other conditions besides urologic ones.

Diane Newman: No, but I agree with you a hundred percent. I mean, I always tell people, it did show us during COVID that we can do telehealth and do that, and we have a lot of what we call benign urologic conditions like overactive bladder that we really can do that way. You're exactly right, and we have more and more sophisticated diagnostics that can be done remotely. So, it's exciting. So I really appreciate you talking with us and thanks so much for sharing this information on this device for BPH.

Steven Kaplan: All right. Well thank you so much and thank you for inviting me and thanks for organizing it.