Minimally Invasive Treatment in Benign Prostatic Hyperplasia (BPH) - Steven Kaplan
December 16, 2021
Steven Kaplan, MD, FACS, Chair of Research, American Urologic Association, Professor of Urology, Icahn School of Medicine at Mount Sinai, Director, Men’s Health Program, Mount Sinai Health System
An Indirect Comparison of Newer Minimally Invasive Treatments for Benign Prostatic Hyperplasia: A Network Meta-Analysis Model - Beyond the Abstract
Minimally Invasive Surgical Therapies (MIST) for the Treatment of Lower Urinary Tract Symptoms and BPH - Kevin T. McVary
Five-Year Rezūm Outcomes Demonstrate Effective Long-Term BPH Treatment
Standardization of 532 nm Laser Terminology for Surgery in Benign Prostatic Hyperplasia (BPH): A Systematic Review - Beyond the Abstract
Steven Kaplan: We'll talk a little about some new therapies in BPH, and I figured I'd have a hot seat in there. These are my disclosures, I'm the PI for both the Urotronic and proverum device, which I'll talk about in just a couple of moments. This is going to be a relatively quick talk, because it's hard to talk about everything new in BPH in about 15, 16 minutes. I'll try to give you some highlights and what's coming down the pike, because I think that's going to be important for you to know as a community with respect to new things that are coming on. In terms of minimally invasive options, the key is to be office based, because for a lot of reasons, easier for patients, reimbursement's a hell of a lot better. And in terms of where people are going, that's the future to try to do as many things through flexible instruments as possible.
In terms of the advanced options, I'll talk specifically about aquablation and some of our experience at Mount Sinai pros, cons and indifference. Why all of this now? Well medical therapy, which started in the 90s, if you will, has become the mainstay of therapy. The problem is, sounds good, looks good, but patients don't stay on it a lot of times. The adherence rate is incredibly low and this is one of the classic studies looking at very, very low adherence rate. And this study was a 71% discontinuation rate. And by the way, this is not BPH medications. You can be on statins, the statin discontinuation rates about 60%. And there's some data that says, no, maybe pretty good saving you from heart attacks and strokes. BPH may not qualify as much, but the point is, folks don't stay on medication.
And now you can see patients on BPH medications, and not just on one, they're on an alpha-blocker, they're on a 5-ARIs, throwing a little tadalafil. Now we'll throw in an overactive bladder agent. But before you know it, a patient for a quality of life is on three or four medications with three or four potential different verticals of side effects. Maybe we should be rethinking about things. In addition, there's now data emerging about long term side effects with using medications. For example, with the 5-ARIs. Some real hard data about dimension, depression, some data about alpha blockers. Do we really want to put a patient on for 20 years out of medication for quality of life? Maybe we should be rethinking that. Our choices of surgical technique is often based on prostate size. And that's really the key that I'll remind you is that minimally invasive therapies and the office procedures tend to do better in relatively smaller prostates.
You can define what is small in your world, but the data is in about 80 grams, top about 100 grams. But most of the patients who are being done are boundaries 40, 50, 60 gram gland. We'll talk a little bit about Waterjet ablation. Again, in terms of the terms we'll use, commonly called aquablation, but we'll term as Waterjet ablation. Just look at the numbers in terms of prostate size, because we always talk about prostate size, but how many patients have big prostates? This is a really good study in about 1700, some odd men that about 20% of men have prostates more than 75 grams. It's the overwhelming minority of men have that larger prostate with about 9% being over 100 grams. And yet a lot of people are fighting in that space. Let's look a little bit about the data.
The prostatic urethral lift, commonly known as the UroLift, been around for a while. I remember meeting the discoverers in 2004 and watching them evolve in terms of techniques and coding and see what's happening. It's been an interesting evolution. The five year and there's some emerging data about six years, it works in those patients it works in. I'm not going to go through the hard data. But the point is, in that those patients in clinical trials, it works and seems to be durable. Caution, when you look at clinical trials for BPH, and frankly, for any surgical therapy, it's only the responders. It's only the folks who continue to come into trials. The patients who don't do well, who don't come back, are not included. Unlike a medical trial, where everybody in is everybody out. It's very, very different.
You are getting the best of the best, because this is almost a responder analysis and that's not just true for urethral lift, it's true for any of these minimal surgical options. This is water thermal therapy, commonly known as Rezūm. And the difference is terms of the way energy is delivered. And theoretically, you get a more homogeneous response in terms of ultimate coagulation necrosis. You can believe or not believe, but here is at least a theory why this evolved. I'll just go through that. This is now five year data. And again, in patients who respond the data is very, very durable. Not surprising, because they keep coming back to the clinical trial for a follow up. And the improvement's about five or six points on symptoms and about three points on flow rate. And by the way, we saw this with microwave and TUNA as well, fairly consistent in terms of what minimally invasive therapies actually do.
Now let's talk about retreatment, because retreatment is in the eyes of the beholder and it depends how you define it. In these clinical studies, the retreatment rate at five years was 4.4%. But that, that does not include the people who left the study. We don't know what happened to them. The way I like to look at the data is at five years, 25% of men in both the prostatic urethral lift and the Water Thermo Therapy trial, they're retreated or out of the study. And that's in my mind, I will look at it in terms of discussing this with patients. Although I will show you some data we just presented AUA, which will surprise you in terms of the retreatment rate. That will how we'll end it.
Now, one of the important things is this is from our new guideline statement is about treatment failure. And we need to have better definitions of what treatment failure is. For some people going, not having to have another surgery, retreatment is a success, but if they have to back on medical therapy, did we really do something good? Is that considered to be something that is a success? Well, some patients may not think that. We have to come up to a consistent type of response in terms of definition that we can do across all of these clinical trials, as well as a lot of these therapies.
Now, one of the things that's interest thing is, is how we carve data up. And this is a very competitive space and everybody tries to carve their data in certain ways. This is a very interesting study that actually came from, [inaudible 00:28:15] I think, was the lead on this. And the bottom line is it looked at the one month effects of having both prostatic urethral lift and water thermal therapy. And I bet, that this is what you find in your own practices for those of you who do them. And that is that the treatment response, at least, the treatment effect seemed to be a little bit easier with the prostatic urethral lift in the first month.
And this looked at various parameters, including symptoms and sexual function and percent of new medications. And you can see again, is it a month? And it's a small trial, but it provides an interesting aspect and that is real world data. And at the end of the day, that's the end of the day. It's not what's in a clinical trial that leads to someplace, but what's your experience. And therefore, the patient's experience is much more important. And you can see here that for various parameters, whether it's symptoms or sexual function or percent back of medication, it's a little bit better for prostatic urethral lift than it is for Rezum at a month.
Now in terms of re-catheterization, not surprisingly, but will also be higher with water induced thermotherapy. Why? Because you get oedema which leads to an eventual coagulation necrosis. In my own practice, having done, well, over 150 of each of these procedures, the patients have it in our office. About 10% of patients with prostatic urethral lift go home with a catheter. All my patients go home with a catheter with water induced thermotherapy. Now caveat, I only do patients with middle lobes. I'll use water induced thermotherapy. Those are patients more likely to go into retention by manipulating some self-selecting, but that's at least one of the things that we do. And you can see in this study, the re-catheterization rate was higher with water induced thermotherapy.
Let me turn out to Waterjet ablation system. Any of you doing this, by the way? Show of hands. Okay. There's one. Hi there. We actually got involved with this, we were one of the clinical investigators for this. It's a very cool technique. And what patients like about it, it's a robotic, if you will, because once you set the probe and the transrectal probe, just step on a button, once you preplan this. What I like to describe it to patients, it's a two dimensional approach because unlike whatever transurethral technique you like, you're going from inside out.
You know where you are on the inside, you know a little bit less where you're on the outside. Here, you can see it three dimensionally because you see it cystoscopically, visually and you can also do it under ultrasound. And doing these procedures under ultrasound has taught me a lot about what we're doing and what we're not doing. It's a lot of fun, the procedure, it's a short learning curve, which is nice because I believe that the homogeneity with this technology will be greater because a probe is a probe. You have to learn some issues about how to place it and arm angling transurethral instruments. A transurethral instrument, it's really learning the treatment patterns. I think it's going to be much faster to learn by residents. In my own experience, having to have five residents, we've done almost 100 of these. The learning curves about four or five patients where I give up the case.
I'm just planning the treatment. It is remarkable, which is good and bad because it's easy to do, but my concern is, is that residents may lose the ability to really learn how to do good to URS or lasers or whatever techniques. We're going to have to see how that evolves. That's a before picture and this is the after picture. And an ultrasound, you see a wide channel. I mean, it's very, very cool. Now I can't tell you that you won't see this with a laser or with a TURP or whatever technique you like, but when you see it under ultrasound, it's a remarkable different approach and you see what you're doing and what you're not doing. Not suggesting that you do your next laser and put a transrectal probe in, but it is interesting learning this with this technology.
This has been our own experience. And this is from about a month ago that I shared. We had 90 patients. We're now up to about, I think, 97. And we'll be about 110 by the end of the year. One to a 14 month follow up, prostate size all over the place. We really have done prostates over 200 grams. Really, it's remarkable in terms of the large size per patients you can do. In fact, I've transfused one patient, it was in that 38 gram patient. To me, it's harder to do it in a smaller prostate because you got less room to screw up, so to speak. With the larger prostate, it's easier to place it.
In terms of retention patients. And the majority of my patients come in with retention, 56 out of 57 voided. Actually now it's 57. He finally voided. The IPS improvement is surgical like, flow rate improvement, TURP laser-like, and everybody who ejaculated before the procedure, ejaculated not immediately after the procedure. And nobody who didn't ejaculate, ejaculated after. It's not ejaculation creation procedure, but it's very easy to preserve it because you see exactly where the [inaudible 00:33:14] is. It's cool.
In terms of summary, it's evolving where it fits. Big prostate, small prostates where the cutoffs are, I don't know, because I'm learning. In my own head, I'm beginning to plant it in patients with 60 grams, 70 grams and above, but we're still learning. By the way, Lori Lerner, who works out in Boston, who's now the chair of the BPH Guidelines Panel, gave me this interesting thing to do in terms of managing patients post procedure, because I used to give them some anticholinergics and then we got all these side effects.
We use Lorazepam or Ativan. It is the sweetest thing ever in terms of management than the PACU in the first two or three days, because a couple of reasons. One is bladder spasms are less, they have less pain. So they have less increase of central venous pressure and venous bleeding. And they're chill and less annoying, which in New York is a big, big deal. Think about Lorazepam in the future for yourself. The cost, it's real because the cost of goods, as opposed to, let's say, a TURP loop is about 600, lasers are over 1000. The cost of the cogs here, the soft cogs, if you will, about 2,500. Reimbursement in New York right now with Medicare is about almost $12,000. It's big dollars. Now that may be transient. A lot of insurance companies are not paying for it. About a third of our patients are paying in cash right now. They're working on getting this with insurances. One of the issues.
Just very quickly through some other, this is the iTind device. How many of you use that? Okay. Good. You've been looking at a lot of these. I don't know where it fits. Kind of interesting that it's being taught to do with the rigid scope. We do it with a flexible scope. Very, very easy to do. Does it work? I don't know. It's FDA approval, we'll take a look. Patients have to walk around with a string out of their pains for six or seven days. In New York that's not uncommon.
Prostate urethral stents, they coming back. And it's interesting because people have that [inaudible 00:35:14] look and they say, "No, are you kidding me?" But in fact, the newer stents are much less metal, if you will. They're very easy to implant and there's some large clinical trials going on. There's a company called Zenflow and they're going to be first at and they're carving the way. I'm the principal investigator for one called proverum or the prove stent. And we'll see where this works. There's a company called Medion. There's a whole bunch of these out there. We'll see where it fits. One of the things to think about is we are now evolving into patients, don't mind having a therapy again. They have Botox again just in our world. That's very common. We'll see what the durability needs to before patients accept it.
I'm also the principal investigator for a Balloon. And you're saying, "Crap, balloons again?" But this is actually, it's a different balloon because, obviously, the technology's a lot different, but it's a drug coded balloon. You're getting a two for one because you're getting paclitaxel being absorbed right at the area where you're doing the anterior commissurotomy. And what's interesting is that because of that, instead of just making the whole wide open, you're actually breaking the anterior capsule, at least, in theory, and hopefully, durability.
I'll just go very quickly through it. Just be aware that it's out there, something called the OptoLum. What's nice about this is the data you is closer to a TURP than it is to prostatic urethral lift or water induce thermotherapy. This is from something called the EVEREST trial, which we did at AUA. There is now the pinnacle trial. I'll have more phase three data results by the end of next year. But the symptom improvement is actually been pretty dramatic and it's more TURP-like than it is prostatic urethral lift or water induced thermotherapy.
Finally, let me talk to you about something of interesting concern, because we have in our mind about the retreatment rates. Patients will ask you, do I need this again? How long is it going to take? We presented some data of a healthcare care analysis data, almost 50,000 patients. And we specifically defined retreatment. You can see the TURP group, the KTP group, the prostatic urethral lift and the water thermotherapy group. The reason why that has the least is because it evolved over when the code. We specifically took patients who had that code. Very quickly, in terms of return procedures, which could be another cystoscopy, a catheterization for clot retention. Look at those rates of the year, water thermotherapy, 23%. KTP, 22%. TURP, 21% prostatic urethral lift. Maybe some of that's not surprising because bleeding and they come back. But let me just show you this one.
Let go back on that. Good. This is the retreatment rate. This is basically, we defined as does the patient need another BPH treatment? It's as simple as can be. I can't make it any simpler than that. This is at a year, by the way. Water induced thermotherapy, 7.2%. Does is seem to match up with their 4.4% clinical trial? Does it? This is at a year. KTP, 5.2%. The historical standard, TURP 5.3% and prostatic urethral lift 5.4%. This is real world data. We're now looking at five year data and these trends are continuing. This is the real world and this is something we need to know and eventually define in terms of re-treatment because that's what actually goes on.
And we'll just skip that in terms of the time. In general, it's evolving. I don't certainly have all the answers. I think you're figuring it out just as fast or as slow as I am, but I think this is going to be a mainstay into of how we treat patients with BPH. Don't believe everything you hear. Certainly, don't believe everything you hear from me. But the bottom line is, is that understanding that the clinical data may not match up with real world data is very important for treatment of BPH. Thank you very much for your attention.
Mara Holton: Dr. Kaplan, thank you very much. That was very informative. And in particular, I'm super interested in aquablation because one of my partners is very, very interested in Aquablation. There's a lot of enthusiasm about that procedure in the community. You did address ejaculatory risks as well as bleeding complications. But can you talk a little bit to things like patient symptomatology in a week or two afterwards, as well as risk of retention?
Steven Kaplan: Right. That's a great question. And the answer is we're still evolving in terms of postoperative management. The patients will bleed a little bit more for sure. And if you look at the initial data, the transfusion rate was around 12%. Now you can't do a procedure if you go going to have a transfusion of 12%. It's not going to work because, basically, we're just putting a catheter in and yanking it and tying it to their kneecaps. That's not going to really work very well. In the second round, what we did in the investigation and now in the real world is with the end of the procedure we TURP, if you will, just the bladder neck. And you remove the tissues and you get the bleeders there and the transfusion rate is less than half a percent.
It's very, very important that you do that after the [inaudible 00:40:23] procedure, whether you do it with a laser or with a loop, I tend to use a bipolar loop and it's worked very well. I've transfused one patient, that was our third patient with the smallest prostate ironically. But if I would imagine that they bleed more, the answer is yes, because again, you have this fluffy tissue that normally you would TURP a laser away, which is sitting there. One of the things we've learned though is with the Ativan, has really helped a lot in terms of chilling them down so they have less bladder spasms. We also put them on both a combination of acetaminophen for a couple of weeks. We're still learning a lot of that issue. In terms of post-op retention, more than half our patients are in retention from the get go. We don't tend to take the catheters out in the hospital. We take it out in the office. But it's been pretty good.
Mara Holton: And then we don't have a lot of time. But one thing that I've noticed in my practice specifically is that there's a vast differential between the way the older clinicians practice, particularly with deference to medical management and then the younger clinicians about acceptance and adaptation to these newer procedures. Can you talk just very quickly through your personal algorithm for patients as you see them and how long you tolerate medical therapy, basically?
Steven Kaplan: I don't tolerate medical therapy at all, personally. But it's ejaculation, it's just terrible. My practice may not be the best practice to ask because I everybody's failures. I don't see any virgin patients if you will. They either have come to me that they've been on medical treatment or they've failed medical treatment. But my tolerance of long-term medical therapies is changing, because I'm really concerned about any long-term medication in any patient, much less drug-drug interaction. And if patients over 63, I think the data is, the average is about seven medications.
Mara Holton: How does that clinically translate when you interface with the patient? Because there's a lot of this, "You're doing great," speaking at the patient and then writing them a script and sending them out.
Steven Kaplan: Right. A lot of those patients come to me because they haven't done well. They haven't had sustainable effects. They have sexual side effects that they're really concerned about. They're also in a lot of medications just for their prostate, which really bothers them. And now it's literally, I've seen patients come to me on four medications because they urinate three times at night. That doesn't make a lot of sense to me. I think when you talk to patients that way they get it as well. And they're always afraid of having surgery, but it's the minimally evasive that may be a good alternative.