Surgeon: Neil Barber

Moderator: Claus Roehrborn


Neil Barber, M.D.

Appointed as a Consultant Urological Surgeon to Frimley Park Hospital in 2005, Neil Barber is Clinical Lead for Urology at Frimley Health NHS Foundation Trust and Director of the Frimley Renal Cancer Centre and the Frimley Benign Prostate Clinical Research Centre.

His particular subspecialist interests in managing waterworks symptoms in women and men, particularly for men suffering with BPH, has led to his involvement in new treatments including the introduction to NHS England of the Greenlight laser in 2002, Urolift in 2014, Aquablation of the prostate using the Aquabeam system and iTind in 2019. Neil has been involved in numerous high quality national, European and global studies as well as acting as an advisor to NICE in this field.

Claus Roehrborn, M.D.

A world-renowned urologist and expert on cancerous prostate diseases, Claus Roehrborn, M.D., has been practicing at UT Southwestern for more than 20 years and has been Chair of the Department of Urology since 2002. Under his leadership, the Department has consistently been named among the nation’s best by U.S. News & World Report.

Dr. Roehrborn’s practice focuses on the treatment of prostate cancer and benign prostatic hyperplasia (BPH). Over the past several years, he has performed more than 1,200 robotic prostatectomies for prostate cancer and more than 800 laser prostatectomies for BPH, making him one of the country’s most experienced surgeons in the use of robotic procedures for urologic conditions. In addition, he is involved in virtually all aspects of BPH research as well as translational and clinical research in prostatitis and prostate cancer.

Born and raised in the former West Germany, Dr. Roehrborn earned his medical degree from Justus Liebig University in Giessen and began his residency in surgery and urology at the German Army Hospital there. He was initially drawn to urology during medical school because of the comprehensive nature of the specialty that allows physicians to see patients, do their own medical tests, diagnose their conditions, operate on them if necessary, and then do follow-up care.

In 1984 Dr. Roehrborn moved to Dallas and continued his studies at UT Southwestern where he received advanced training in urologic endocrinology. He became a faculty member of UT Southwestern in 1992.

In 2018, Dr. Roehrborn was included in D Magazine's Best Doctors list and was named a Super Doctor by Texas Monthly. In 2010, he was the recipient of the Patricia and William L. Watson Jr., M.D., Award for Excellence in Clinical Medicine, which recognizes a UT Southwestern clinician whose work exemplifies a commitment to outstanding patient care and advancement of innovative medical therapy. The recipient of the award is chosen by a panel of colleagues and peers.


 

Webinar Transcript

Dr. Krambeck:

Thank you all for joining us today for our master class in endourology. This is sponsored by the Endourology Society and the Society for Urologic Robotic Surgeons. It's also sponsored by Cook Medical, and we appreciate their grant in supporting this educational activity. This is our mission statement, you can see our purpose. The target audience is physicians who are looking to learn new surgical techniques. And you can obtain CME credit for this course. You will receive a link via email at the end of the month to claim your credit for this activity.

Dr. Krambeck:

Today's course is on the dilatation in the treatment of BPH. I'm very excited about this because this is an area that I know very little about, and so I look forward to the presentations. We have Dr. Neil Barber. He is a consultant for urological surgery at Frimley Park Hospital. He's been there since 2005. He's the director of the Frimley Renal Cancer Center and the Frimley Benign Prostatic Clinical Research Center. Dr. Barber sub-specializes in BPH. He specifically looks at new treatments, including the introduction to NHS England, the green light laser in 2002, UroLift in 2014, aquablation of the prostate using AquaBeam System, and the iTIND 2019 for which he will be speaking today. Dr. Barber has been involved in numerous high quality national, European and global studies as well as acting as an advisor for the NICE in this field.

Dr. Krambeck:

We also have Dr. Roehrborn, who I think needs no introduction. He has been practicing at UT Southwestern for more than 20 years and has been chair of the Department of Urology since 2002. Dr. Roehborn's practice focuses on the treatment of prostate cancer and benign prostatic hyperplasia. He's done over 1,200 robotic prostatectomies for prostate cancer, and more than 800 laser procedures for BPH. He's involved in virtually all aspects of BPH research, as well as translational and clinical research in prostatitis and prostate cancer. Without further ado, I will turn over the platform to Dr. Roehrborn.

Dr. Roehrborn:

Thank you very much Amy. The reason that you're not so familiar with the dilation is probably because in your practice you treat a lot of very large prostate with the HoLEP procedure and so, as you know, when we're talking about the dilation procedures as today, this focus is on prostates a little bit smaller than what is your normal size range, I would say.

Dr. Roehrborn:

Today we're talking about mechanical ways to dilate as Dr. Krambeck said, the prostatic urethra. This is part, of course, of minimally invasive surgical treatments, and part of my introduction will be to talking about why the need for minimally invasive surgical treatments at this time. These are my disclosures. I'm an investigator for several of the companies in this space, and consultant for the same companies and for some other companies.

Dr. Roehrborn:

This slide here shows the world population pyramid for the years 1950, 2017 and 2100, and what I want to show you is the projection for the year 2100 in red. I hope that this is visible. I have really a mixed message on my computer.

Dr. Barber:

Yeah. No, it is visible.

Dr. Roehrborn:

Okay, so what you say here is basically by this red curtain rising, that as we move onward in this century, that the population will get older and older and more and more patients, men and women, will be in their 60s, 70s, and 80s, which is of course the age range in which BPH and lower urinary tract symptoms are so common. In fact, this estimate here for the United States and for other developing countries, suggests that the population 65 and older will increase from 35 to 70 million between the years 2000 and 2030, and this is even more dramatic in some of the developing countries.

Dr. Roehrborn:

Medical therapy is really the mainstay of that treatment at this point. You can see here, from the current MLUTS BPH Medical Management guidelines, that patients after initial evaluation are guided towards a stratified approach of medical therapy, be it with an alpha blocker, be it with a PD5 inhibitor, be it perhaps with a combination of antimuscarinic and [inaudible 00:04:38].

Dr. Roehrborn:

Now, medications are very, very common increasing in popularity still in most countries. This is a slide showing a study from Dr. Lucacs from France, demonstrating the increase in the first decade of the century in the use of medication, Monotherapy, Bitherapy, even Tritherapy, with three different drugs, in France. You can see the linear increase in the population popularity in the use of drugs.

Dr. Roehrborn:

Now, on this slide, you see a flip side of the medical therapy, namely the poor compliance. This is the first point I want to make, namely that the compliance of medical therapy is in fact so low that after a year, two years, three years, and four years on medical therapy for either an alpha blocker, 5-alpha reductase inhibition, or from combination therapy, the compliance goes way down to under 20 percent as you can see.

Dr. Roehrborn:

As the next slide shows, if you don't take your drugs, you don't have the benefit of the drug. There is a little highlight here on the slide, on the right-hand slide when it talks about drug adherence. What you can see there is, that patients who don't take their drugs, for example here, the 5 hour ARI, they do not have the benefit to reduce the prostate size and prevent surgery. Clearly, lack of compliance, lack of adherence, leads to lack of therapeutic efficacy.

Dr. Roehrborn:

Now, the traditional surgical treatments, such as ablative surgery, open enucleation, TURP, et cetera, and laser ablation, also have retreatment rates, and this slide shows from the same paper by Dr. Lucacs, the percent of patients without new BPH surgery or treatment after their initial surgery, you can see that there's also an attenuation over time. In the same paper, he reports that even after a successful surgery, ablative surgery, many patients go back on drugs for symptomatic recurrence or ongoing storage symptoms as the case may be.

Dr. Roehrborn:

There are other studies, for example, this study is from the United States by Strope, and it shows that after laser and electrocautery surgery, there's a very high rate, and at three years after surgery, it can be stated that 22 percent or so of patients are back on medications.

Dr. Roehrborn:

The last example that I want to use is a paper by Campbell, the next slide. This paper by Campbell from 2019 shows again, a utilization of drugs after a seemingly successful surgery that can be as high after 90 days as 15 to 27 percent, and after 10 years as high as 40 percent.

Dr. Roehrborn:

These are problems with the most common form of treatment, which is the drug treatment, and with the second most common form of treatment, ablative surgeries, which doesn't always work. There's one other point I want to make, and I call this the window of opportunity. The window of opportunity, next slide, this is an animated slide, you'll have to just keep working with me. The window of opportunity slide asks the question, is there a perfect therapeutic window of opportunity. Is there a time during which the treatment is most effective in treating LUTS or preventing progression, or is there such a thing as missing that therapeutic window, just as this young man here is just about missing the window of that car driving by.

Dr. Roehrborn:

Now, let's animate this slide, and so I talked about the window of opportunity, and how one can miss a window of opportunity. Here, I want to make a practical example. This is a cartoon, and it's not really true in terms of the X axis of the Y axis and the timeline, but we know that the prostate grows, shown in blue. We know that the symptom severity increases with age, shown in red. We know the prostates grow, shown in green, and we know that all along there are other things taking place that we don't know so well, like the bladder wall thickens, trabeculation ensues, bladder compliance reduces, and detrusor overactivity may develop.

Dr. Roehrborn:

Even more insidious, in patients with long standing BPH, detrusor underactivity, essentially a point where none of our treatments are any longer effective, can occur. What we currently do is we currently trigger our treatment decision solely based on symptoms and bother, and we say that somewhere in this continuum, we in starting our medical treatment or surgical treatment, and I late in my career, have come to the realization that in some patients we offer such surgeries too late. We wait too long. We wait on this continuum until trabeculation, lack of compliance, DO and detrusor underactivity is to a point where medications don't work and even surgeries don't work.

Dr. Roehrborn:

This raises a question in my mind. Is there a good opportunity to insert minimally invasive treatment with less like complication than a surgical ablation into this mix, and these treatments would be the minimally invasive treatments. One such treatment is the UroLift treatment, and I will show you a ten minute video that is both education illustrative, it makes some point about good techniques, bad techniques, what can go wrong, and how it works in an ideal world, and then I'll close my presentation out with a few data slides.

Dr. Roehrborn:

The UroLift Implant you are well familiar with is a permanent implant and it consists, as you can see of the nitinol stainless steel anchor and the string that connects inner and the outer anchor. It is a one-time use device that is inserted as [inaudible 00:10:21] transurethrally, and the goal of the treatment is, basically as shown in the middle panel here, to compress the lateral lobes of the prostate in the interior chamber at ten and two o'clock to the side, and by applying these devices from the bladder neck moving downward towards the verumontanum, in a systematic manner to achieve an opening, as one can see perhaps on the right lower image of this particular panel.

Dr. Roehrborn:

The mechanism of action of the device is first and foremost a mechanical opening from the bladder neck to the verumontanum, but in the long term, it is possible that there are other phenomena taking place. For example, the device causes some degree of ischemia, there may be some tissue remodeling, there may be focal atrophy, and to be honest, nobody really knows in the long term if these prostates grow at a similar rate, a different rate, than normal prostates, and nobody has really done long term studies in terms of PSAs. These are unanswered questions.

Dr. Roehrborn:

At this point, having introduced this technology, this particular dilation technology for men with MLUTS and BPH, I'd like to suggest that we'll run the video now.

Dr. Roehrborn:

Hello, my name is Claus Roehrborn, and I'm a urologist at UT Southwestern Medical Center in Dallas Texas. We'll show you a brief video about the technique and the actual implementation of the UroLift device. We'll use some actual patients of mine, and I'll try to show you both endoscopic pictures as well as the handling of the hand piece outside the body, to give you a feel for a proper placement technique so that the UroLift devices end up both away from the bladder neck and nicely staggered alongside the urethra, and as I feel is important, perpendicular to the axis of the urethra, which is key of the way that this instrument should work.

Dr. Roehrborn:

We'll enhance this video with some cartoons and some drawings, and I hope it will be both entertaining a little bit, but also in the end, educational, to make this treatment of this device, work to the very best interest of your patients.

Dr. Roehrborn:

This cartoon shows the typical setup for the placement of the UroLift device. The cartoons on the upper right hand corner show the insertion of the cystoscope, the bending of the cystoscope towards the patient's right side, and the firing of the first clip close to the bladder neck. The lower half of the cartoon shows the first clip on the patient's left-hand side, approximately 1.5 centimeters away from the bladder neck.

Dr. Roehrborn:

Here the device is inserted, pulled back, angled about 20 degrees, tension is applied and the first needle is applied on the patient's left hand side, 1.5 centimeters behind the bladder neck. The device is then straightened out and reinserted in the bladder. This is the normal and recommended strategy to place the UroLift devices in the interior chamber of the prostatic urethra.

Dr. Roehrborn:

Here is our first patients. The device is pulled back, beyond the bladder neck, approximately 1.5 centimeters, and in this instance we are identifying the verumontanum, moving forward, and then bending the device approximately 20 degrees against the midline, and then firing the first device on the left-hand side behind the bladder neck, as shown here in the anterior commissure.

Dr. Roehrborn:

The second device is placed in a staggered manner, just ahead of the verumontanum. We need to remember that the device fires forward, and so even if we do see the verumontanum, the device will end up well ahead of the verumontanum and not within the proximity of the external sphincter. Here, we see the first application on the right-hand side in the interior chamber, at approximately a ten o'clock position. The device is released, the next device is loaded, we move back until we see the verumontanum, angle upward, approximately ten o'clock, and fire the second device on the right-hand side, staggered, and a little bit lower than the first one, to open the interior chamber and the prostatic urethra.

Dr. Roehrborn:

After this first patient, we want to look at a model to understand how the device operates. Here in this model, the cystoscope is inserted and then pulled back, again, about 1.5 centimeter from the bladder neck. The device is then angled by about 20 degree against the right side, in this case, where we wish to apply the first clip. I indicate the angulation here. It is important here to recognize that the device fundamentally fires forward, as we see here. The needle will come out, and if we bend it about 20 to 25 degrees it will come out perpendicular to the axis of the urethra.

Dr. Roehrborn:

I insert the device again, and pull it back for second application, closer to the verumontanum. It would be incorrect to apply it here, because this clip would end up in the middle of the prostatic urethra, as it fires forward. Rather, I pull back until I see the verumontanum and the open slot, then bend it to 25 degrees against the right-hand side, and then fire. The needle will end up perpendicular to the axis of the urethra, and about a half a centimeter ahead of the verumontanum and well away from the sphincter.

Dr. Roehrborn:

Again, the device is inserted and pulled back, and in this particular instance, we demonstrate how not to release the clip. We pull back, but not quite far enough, and we don't bend and the needle ends up inside the detrusor of the bladder, as seen here. Because again, the needle angles forward, and moves forward, and without bending the device it will occasionally end up in the detrusor muscle.

Dr. Roehrborn:

Here we are live with our second patient. The first device has been placed on patient's right-hand side, close to the bladder neck. The second device is placed by pulling first back, visualizing the verumontanum, then angulating and firing the device. On the left-hand side, we pull back 1.5 centimeter from the bladder neck, lift up the lateral lobe, bent in and now watch that the device is angulated against the midline. On the right-hand side you can clearly see it. Compression is applied, and the device is fired by releasing it, firing the needle, then moving gently forward until in the window the wide line appears, and the device is clipped.

Dr. Roehrborn:

Here the second round of application. The device is pulled back, angled towards ten o'clock, moved in this case 20 degrees against the right side, as indicated here by the hand motion. It is released and fired, and then gently move forward until the wide line appears, and cut.

Dr. Roehrborn:

It is exchanged, and now we're moving to the fourth clip, the second one on the left-hand side, in close proximity and just ahead of the verumontanum. Here we see our first clip, we'll pull back further, bend 20 degrees, fire, and then watch until the wide line appears by moving the device forward and cutting. In this particular instance, the first clip on the left-hand side did not take care of the lateral lobe adequately, so with this clip is placed asymmetrically only on the left-hand side, close to the bladder neck. Great care is taken to move back far enough so that the clip does not enter the bladder. You see the bending of the instruments, 25 degrees against the axis, it is released, cut, and now when we move the instrument in and come back, we see a nice opening, symmetrical of the prostatic urethra, and the wide open bladder neck.

Dr. Roehrborn:

In this case, it took four clips, two on each side, plus one additional clip asymmetrically placed at the bladder neck.

Dr. Roehrborn:

This is a patient referred to me after an outside UroLift with severe irritative voiding symptoms. We see in the CT scan, shown here in two different orientation and of the right-hand side, the actual endoscopic picture, that the clips all were placed very close to the bladder neck, and in fact on the right hand side one clip ended up inside the bladder and had formed a stone, seen by the white encrustation. Now, we animate the coronal cut, and it again shows the clips all too close to the bladder neck, and one of them having formed a stone inside the bladder as seen here.

Dr. Roehrborn:

This may happen if in fact the bending is not observed. Again, here is a cartoon showing the enlarged prostate. Step one, the insertion of the instrument. Step two, angling 20 to 25 degrees, in the direction of the clip and then releasing it. It is shown here again, on the left-hand side in the straight orientation and the right-hand side bent.

Dr. Roehrborn:

Another live case, first clip on the right-hand side, ten o'clock in the interior commissure, 1.5 centimeter away from the bladder neck, release. Reloading for the second clip, 1.5 centimeter behind the bladder neck, two o'clock on the left-hand side, firing the clip, compressor, cut, and release.

Dr. Roehrborn:

Third application on the right-hand side. The verumontanum is seen at the bottom of the screen, and we know we are firing forward, ahead of the sphincter, ten o'clock to the right-hand side, release, and reloading, and now the last and fourth clip. verumontanum is clearly seen at the bottom of the screen. Two o'clock, bending, firing, releasing, and the interior commissure, and the chamber of the prostatic urethra is nicely opened.

Dr. Roehrborn:

In this particular instance I took a KUB in recovery, and all four clips are seen on the right and the left side of the urethra. This is an older CT scan of the same patient, overlaid, and here I illustrate the prostate and demonstrate that all four clips are within the prostatic urethra, perfectly placed, perfectly staggered, and under tension, opening the prostatic urethra. I would consider this as the ideal outcome of a UroLift procedure in this patient, and in fact, this particular patient had an excellent clinical outcome.

Dr. Roehrborn:

In this video, we visited the basic technique of applying the UroLift device, which in my opinion, is paramount to a successful outcome. Moving back from the bladder neck, angulating 25 degrees on either side, and then firing with considerable pressure to the sides, and releasing the device.

Dr. Roehrborn:

At this point we are going back to a few data slides before I turn it over to Mr. Bower. I wanted to show you the five-year data here on this slide. The five-year data for the symptoms score show relatively good improvement. You can see that the symptom score from baseline goes from 21,22 to 13.9. It attenuates a little bit a 5 year, no doubt. The same is for the quality of life and for the flow rate, but the flow rate improvement is still 3.5 millimeter a second at five years.

Dr. Roehrborn:

Shows actually the flow rate data, but we can move on to the next one, we had that in the previous slide. One important part of the missed treatments, and I'm sure that Mr. Barber is talking about that as well, is the maintenance of both erection function and ejaculation function, and the MSHQ score is suddenly the hotbed of this war of minimally invasive treatments, because every company administers both the ejaculatory function and bother score to show that their device basically leaves ejaculatory function alone. For the UroLift, over five years, there's virtually no change in ejaculation function and in ejaculation bother.

Dr. Roehrborn:

This just demonstrates, if you stop for a moment, that the AUA guidelines in the most recent update from 2020 recognizes both the UroLift and the [inaudible 00:24:22] water vapor treatment as the two minimally invasive treatment currently offered by the AUA guidelines in the United States, but you also see that it's restricted to under 80 grams, although the FDA approves it for up to a hundred grams, and absence of a middle lobe, because as I stated before, the AUA guidelines recognizes the single arm trial not as strong enough evidence, so it's in the eye of the beholder. By AUA guidelines it's 30 to 80 grams at normal to low.

Dr. Roehrborn:

On the market currently under development are at least four or five mechanical devices. One way or the other they all got inspired by the UroLift and there is the company called Medion, they're making a device called Exflow. There's a company called the ZenFlow, they make a spring. These devices are either temporarily or permanently implanted, and one of them that has seen a lot of trial work in Europe, specifically in Italy and also in western Europe and in the UK, its the device by Medi-Tate. It's called iTIND, Temporary Implantable Nitinol Device, and it's shown here in a graph and a cartoon.

Dr. Roehrborn:

I'll use that as my transition to turn this over to Mr. Bower who has experience with it and will talk about it and show the data which is achieved with this particular device. I'd like to point out, and this will come out that this is a very different device, because it's implanted and later on removed. The UroLift device stays in, right? So these are two very different approaches that both have good data to support them. The iTIND device is not approved in the FDA, it's approved by the FDA but not by the AUA guidelines. Recommended, but I believe the NICE guidelines do actually acknowledge the iTIND device in the UK.

Dr. Roehrborn:

I'll turn it over to Mr. Bower who will talk about iTIND device, or to Amy [inaudible 00:26:10] who was moderating the spot.

Dr. Barber:

Thank you very much Dr. Roehrborn, that's very kind, and a pleasure to hear you talk as always, and thank you very much for the invitation to speak today about a very niche part of the broad spectrum of minimally invasive surgical treatments for BPH that are now available, specifically those that aren't focused on any form of heat, essentially. We're looking UroLift but also, as Dr. Roehrborn mentioned, there's a whole number of other devices coming along, and probably the one most advanced in them all is iTIND, specifically, as he mentioned, with some history in Europe.

Dr. Barber:

My task then was to speak about the iTIND, which stands for the Temporary Implantable Nitinol Device. The form of it that's currently available is a second generation device. I'm just going to get rid of that, sorry. As was mentioned, this is temporary, in a sense it's very different then from UroLift, and for some men then that may be something which is attractive in a sense that nothing is left inside the body, and maybe that's something we can touch on at the end of this, as with all the scare about meshes, as some interesting stuff has come out, sort of NHS in England about registries for any form of implantable treatment, which has come as a bit of a surprise.

Dr. Barber:

The iTIND itself is temporarily placed in the prostatic urethra for five to seven days, and is very quick and very ambulatory. Essentially, it consists in terms of the device of three struts, which create through pressure necrosis over that period of time, three longitudinal incisions. The other part of it is like a tongue, a leaflet, which anchors the device in place, being pulled back just beyond the bladder neck. Other than that, there's a small retrieval suture, which I'll illustrate later, is used to remove the device.

Dr. Barber:

What you're hoping to achieve is three longitudinal incisions, a bit like a Mercedes Benz, one at 12 o'clock, as you can see in the middle there, and on the left at seven o'clock and on the right at five o'clock. It's really an up and down incision which the device creates.

Dr. Barber:

As Dr. Roehrborn mentioned, it has been through NICE, but it didn't gain formal recognition. This is through a committee called Interventional Procedures Committee, which give guidance on new devices, and the guidance it gave was that the evidence at that time, and this was submitted towards the end of 2018, suggested that that data gave them only the ability to recommend this to research and there were ongoing trials at that time.

Dr. Barber:

I've introduced it to the NHS through my hospital under the banner of a prospective audit and study.

Dr. Barber:

There have been three main studies, either published or presented, and these are the baseline characteristics from them. MTO1, as we'll see in a minute, was the initial study using the first generation iTIND in [inaudible 00:29:04] with Professor Porpiglia who's really been heading this up in terms of introducing this device. MTO2 was a multi-centered pan European non randomized but prospective trial, which we'll have a look at. MTO6 is another multi-centered European trial which the results of which were recently presented at the AUA.

Dr. Barber:

As you can see here, I'll draw your attention to a number of things. The age of the patient is as one would expect, but note the prostate volume, and as Dr. Roehrborn alluded to, we're not talking about the type of prostate volume that we see across the board in all patients with bothersome urinary tract symptoms, but specifically those with smaller prostates, and if anything with the iTIND, certainly in my opinion, you're looking at the smaller range of that, and that's reflected in the prostate volumes, as recorded in these trials.

Dr. Barber:

Beyond that, they have the normal level of moderate severe lower urinary tract symptoms as scored by IPSS, and flow rates suggesting obstruction. With all these trials are the same set of exclusion criteria, which are pretty much the standard ones that we see in these minimally invasive surgical treatment trials. Specifically, the aim was to exclude people with a significant Intravesical Prostatic Protrusion in terms of a middle lobe.

Dr. Barber:

This just gives some illustrations of the type of shape of prostate that might be suitable. This by no means is definitive in the current idea of where it may lie. On the left, you can see a high, tight bladder neck. For me, this is the perfect shape of prostate for this device. Again, we can discuss later how one starts to select between these different minimally invasive surgical treatments.

Dr. Barber:

A small median lobe in the middle, possibly continues to be suited for this device, however on the right there, we see a prostate with a large, occlusive, [inaudible 00:30:57 if you like, type middle lobe, which certainly, evidence suggests is not suitable for this procedure.

Dr. Barber:

As I mentioned, it's really those patients with a high tight bladder neck, where the lateral lobes really aren't the issue in terms of the obstructive element of the prostate.

Dr. Barber:

Just to go through the data quickly, the MTO1 as I mentioned was the original study from Turin and there's now the three year follow-up from this single center with Professor Porpiglia, and [inaudible 00:31:28] 50 years, with prostate volumes less than 60 mils, but as you may remember from the previous slide, the average prostate volume was much smaller than that.

Dr. Barber:

If we just show quickly some graphics of that, you can see that over those three years, we see a significant improvement in IPSS, and then flow rate, not dissimilar to what was shown previously with UroLift, and indeed is what we see with resume, and although the graph certainly seems to be turning in the wrong direction at three years, it remains significantly better than before treatment.

Dr. Barber:

MTO2 again as I mentioned was a multi-centered pan European trial, so again, Italy included, but also this is one I was involved in in the UK and other centers in Belgium and Switzerland. Eight sights all in all. Again, I'll just skip to the graphics for ease of understanding, but again, this is being published now with two year follow up data, seeing a more consistent drop in IPSS and in improvement in flow rate, much as we see with the other minimally invasive surgical treatment, and the same results with quality of life scores and post-void residual volumes.

Dr. Barber:

What's interesting to see and this is now the second generation device, as with the first and now in a multi-centered setting, we're seeing that this non-heat based approach once again seems to be associated with absolutely no impact upon sexual function in terms of ejaculatory disfunction or erectile disfunction.

Dr. Barber:

We can run through the ins and outs of the procedure in terms of the experience of the patient, but you can see particularly when the device is in there it's quite common to have visible hematuria, as one might expect with a device sitting in the prostate and pushing out and creating these longitudinal incisions through pressure necrosis, there is associated urgency and indeed discomfort. Happily urinary retention is rare, our figures are 10 percent in that study, probably overestimate the reality of it, and certainly when one has to part a catheter, albeit a fine one, through device, one worries about displacement of it.

Dr. Barber:

A closer look was made of the MTO2 data, particularly as at that time there was no clear understanding as to the best shape or size of the prostate for this device, and a number of patients had significant middle lobes. Subanalysis suggested that it was this group of patients who has dominated those who did not achieve a good outcome from this treatment, and hence going forward why the advice would be to not to deploy this device in men with significant intravesical protrusion of a middle lobe.

Dr. Barber:

Finally, then, there's the MTO6 study, which was recently presented. Again, this is multi-centered European, dominated through Italy but also Spain. Again, assessing in a multi-centered manner, in a prospective manner, the outcome of this second-generation iTIND. We'll just go to the slides.

Dr. Barber:

Once again, this study demonstrates the same kind of improvement in IPSS, flow rate, and quality of life as we've seen previously. If we overlay those graphs of those three main studies, we see that these results are reproducible which is important and near tracked. UroLift's been very good at demonstrating an importance of reproducibility of outcomes of these minimally invasive surgical treatments, and that's true as regards to IPSS, and also to some degree improvement in maximum flow rate.

Dr. Barber:

By the end of this year, there will have been more than 400 patients recruited into studies for this device, which is good, and the final icing on the cake if you like will be the publication of the MTO3 study, which was the study randomized against Sham as has been performed for both UroLift and the pool study and for Rezum, and it is this which has allowed iTIND to be granted FDA De Novo classification in February of this year.

Dr. Barber:

The data has not been published as yet, and therefore I cannot show it to you, but I would imagine it's in line with the previous published data, hence the badging if you'd like, from the FDA this year.

Dr. Barber:

Going forward, they are looking at a number of other studies, including a potential randomized study against TURP, being a standard of care. I know for these minimally invasive surgical treatments, it's difficult to start thinking about how one might compare such treatments against a so-called standard of care, whether that standard of care should be medication or whether it should be [inaudible 00:36:22] or explorative surgery. Certainly of course, UroLift, [inaudible 00:36:26] and ran Europe through multi-centered BPH6 study, which Dr. Roehrborn touched on briefly.

Dr. Barber:

I'm just going to share a couple of videos now because I know this is new, which hopefully in a very slow manner, but demonstrating exactly what the procedure is, it's very straightforward, very easy, and very easy to... Here we go.

Dr. Barber:

Initially we have a animation. The procedure starts off using a rigid cystoscope, which is passed down into the bladder, that allows a view of the prostate, and it's shaped to make sure that you're happy it's the right kind of prostate for this device and this treatment. You remove the scope and pass the device in. I'll show again in some proper footage, how that is done. Once it's in, you rotate it and make sure it's positioned properly, particularly to that tongue is in the right location, as you then withdraw the device, under vision, into the prostatic urethra. That tongue needs to sit at six o'clock.

Dr. Barber:

As you retract it into the prostate, it just flips over the bladder neck, and once in position, that is the procedure completed. You can see it literally takes minutes and can be performed under, I'd do it under sedation, but I gather some people are performing it under local anesthesia. You're then left with this suture, which is the retrieval suture, the device is left in place for five to seven days, and it's really during the first two or three days, however, that that incisions are really made, and I think after that it's just gilding the lily a little bit.

Dr. Barber:

At the end of that time then, you use the suture to pass through an open-ended 22 french catheter, pass down the urethra such that it engages with a little plastic knob there, and once you've done that, you can pull and compress the iTIND device back into that catheter, and remove it. Certainly, in Turin, Porpiglia's team will remove this under local anesthesia. I still do it under a little bit of sedation because I think that's what I would like.

Dr. Barber:

That's just a little animation. Now we've got a film of the process in real life. This is part of the training program that Olympus, who are now distributing the device, have.

Dr. Krambeck:

Dr. Barber, you said this is done under general anesthesia, or sedation?

Dr. Barber:

I do this under sedation.

Dr. Krambeck:

Okay.

Dr. Barber:

Both in insertion and the removal, mainly because it's new, and I'm relatively new at it, over the last year or two, I'm keen to examine how things look at the end as well, so you don't really need to perform a cystoscopy afterwards, but I like to, just so I know what it's done.

Dr. Krambeck:

Okay.

Dr. Barber:

Just to confirm, you can't hear the audio on this film can you?

Dr. Krambeck:

No, we cannot.

Dr. Barber:

Okay, so I can talk freely.

Dr. Barber:

It's just to say, it is a 19 French or greater cystoscope and again, just having a look, and this is a small prostate, probably not much more than 30 grams, 35, with a high neck. It is this subgroup of patients that I believe that this may have a unique selling point in. They remove the scope, leave the sheath in place. This was the device here.

Dr. Barber:

There's a delivery device that you'd pass into the sheath. Then through that you can advance the device all the way into that, and you feel it kind of pop into the bladder once it's left the cystoscope.

Dr. Barber:

You remove the introducer sheath, and then remove the cystoscope sheath, and then you reassemble the cystoscope and pass it alongside the device. I try and make sure that I keep that device at six o'clock, just below where I'm going rather than to the [inaudible 00:41:07], which it helps to ease rotation and withdraw, be it's in quite a tight space, obviously, in terms of trying to maneuver things. Now we're passing into the bladder, and we can see the device sitting in the bladder with the plastic knob that we talked about for retrieval, and you then have got to rotate it, which can sometimes be tricky because if things are a little bit wedged together, but in this case you can see it rotate very nicely, and you can clearly see that tongue.

Dr. Barber:

Then, you've got to find a position where you can pull it back and view that tongue in particular, so you can see it coming in. You can see all the device there. There's the tongue. Just trying to get the telescope in a position where everything will come back. Here we see now, here's the tongue coming over the bladder neck [inaudible 00:41:53] and it slides over into place. That's the perfect position, and that is procedure done.

Dr. Barber:

You remove the cystoscope once you're happy. I tend to cut that which releases the string, and you can remove the knot, which they call the guide wire.

Dr. Krambeck:

Dr. Barber, this looks fairly straightforward. How many procedures do you think someone needs to watch before they're capable of doing this?

Dr. Barber:

Three or four, tops. It's really about handling of it, just getting it so you can rotate and move things and have a good vision of the device, that it's well positioned. Obviously if you fiddle around, you will kick off bleeding and start to lose vision, so that's when it gets a little bit trickier, but if you do it in one smooth movement, and you get it in place first time, then it's very straightforward.

Dr. Krambeck:

Okay.

Dr. Barber:

Now, this is retrieving it, five to seven days later, and you use a snare passed down a 20 French open ended catheter, making sure that it comes out the hole that you think it is right at the end. Grab the retrieval suture, with the snare, then pull that through the catheter. I often ask the scrub nurse just to hold things, because you want you keep [inaudible 00:43:35] tension. A bit more jelly. Then you just want to keep things taut, because you want that catheter to go down straight and engage that plastic knob on the end of the iTIND device.

Dr. Barber:

Once you feel that, you then will now keep that still and pull the iTIND back into it, and there we are, that's the iTIND being pulled back into the catheter. This is a cystoscopy performed afterwards in this patient, so this is the same patient. You can see what it's done is really made a high and low 12 o'clock incision through the bladder neck, relieving that point of instruction. There are also incisions at five and seven which appear somewhat shallower, but are in fact down that way as well, we can just see them down there. That's it there.

Dr. Barber:

As you can see, it's really opened up that bladder neck which was the presumed area of obstruction. That concludes my short information, what is a very new device, and as I say, now has FDA approval as of this year. The company themselves remain involved in the idea of getting further data and so there's a number of trials, both running in Europe, and also, as I say, there will hope to be a trial, which is a randomized trial, multi-centered in Europe versus TURP.

Dr. Krambeck:

Perfect. That's fascinating presentations. I've learned a lot today. There's been several questions, and Dr. Roehrborn's been answering them live on the type room. There's several for you as well, Dr. Barber. One question is, what if the tongue doesn't fit at the six o'clock position? Would you extract it, reposition, what exactly would you do there?

Dr. Barber:

If you don't position it right, I mean, it has to be positioned right, otherwise the device may fall into the bladder, or worse, I guess, even slip towards the apex of the prostate and start to put pressure through the sphincter, so you need to make sure it is positioned correctly. There's not so much worry about the latter, but the former. I'd advise the patients runs around with it for a number of days and it's not set properly so won't create the incisions properly, so you've got to make sure it's in the right place, and if it's not, then you will need to collapse it, and that's usually best performed by collapsing it into the cystoscope sheath. You just advance cystoscope over it. You put that guide wire back through the cystoscope sheath and just collapse it into it and then you can start the procedure again.

Dr. Barber:

As you say, the difficulty, the more you start doing that, then the prostate will start to bleed, your vision starts to get more difficult, so you want to really pull this off in your first move if you can.

Dr. Krambeck:

Is that why you would avoid anticoagulated patients for this procedure?

Dr. Barber:

Yes. A bit like my feeling generally about the minimally invasive surgical treatments is the driver, rightly or wrongly is about men who are looking to preserve sexual function, and almost by definition they don't tend to be the people who are on anticoagulants because they've already got other forms of vessel disease elsewhere. That's often why they're on their anticoagulant, and sexual function isn't most commonly their driving force, if you like, so there's a certain self-selection that goes on in terms of men who are interested in a procedure which will not be as effective, may not last as long, but will preserve their sexual function.

Dr. Krambeck:

Okay. What is the chance of the device will dislocate back into the bladder?

Dr. Barber:

If you've positioned it correctly, then the word is, if you'd like, and the evidence so far, is that it will not move. My concern is when people don't void. This isn't a new thing, I haven't done a hundred of these. I've had one patient who didn't void, and we had to try and slip a catheter alongside, and of course you don't really know whether you've dislodged the device at that point. You just don't know, so they should void, because if anything, the prostatic urethra bladder neck's held open a lot more widely than ever before with the device in place.

Dr. Barber:

I like to give, sometimes, if I'm worried about them, a small amount of furosemide towards the end just to get them voiding quickly.

Dr. Krambeck:

Perfect. Dr. Roehrborn, I know you answered these typing, but I think, for the whole group, with the UroLift device, what do you do if it misfires? How do you remove the [crosstalk 00:48:13]

Dr. Roehrborn:

There are several kinds of misfire. The first one, if it's a misfire, and you see the device ends up in the bladder, well, you can't leave that, so you can use endo scissors and cut the suture, and then pull both ends out. Freshly implanted you can do that, and you absolutely have to, because that could lead encrustation. Other kinds of misfire, you just don't know. You don't know if you got the right angle and the right positioning. You see inside, where the clip ends up, but you don't see the auto clip.

Dr. Roehrborn:

Acutely, people wouldn't really know that things went wrong. Sometimes, I see patients where they have one or two or even more than two clips seemingly piled on top of each other, and that's an application error, where the doctor put them in the same place, the same place two or three times over.

Dr. Roehrborn:

If a resident would do that, I would probably take one and cut it back out, because I see no point in having them pile on top of each other. By and large, what I recommend to our residents, and I do it in ever case that I do in a surgery center or in the hospital, in the clinic it's a little different, I do a pelvic x-ray, and the pelvic x-ray is the single best way to see the clips. If you'll do a single pelvic x-ray, including the pelvic bone, you can see the inner anchor and the outer anchor, and they should be perfectly lined up top to bottom and right to left, equidistance and vertically oriented, and I put that in the chart. That's my placement confirmation, and it's better than a CT scan actually.

Dr. Roehrborn:

Acutely, if it's in the bladder, or it's a double clip in the same spot, I cut the suture, take the clip out. If it's in the prostate, and I think it's wrong, you can only cut it, take the inner clip out, the outer one is gone. If it's a chronic thing, you get a patient back six months later, there's a calcification or an encrustation, it's a lot harder, so then cutting the suture is not such an easy task. Then you have to usually grasp or get the stone off, get the outer anchor out, sometimes you have to resect it. If you resect it, use a [inaudible 00:50:20]. In one case, I broke two of the bipolar loops. They break easily on the suture. For some reason the bipolar loops, both Olympus and Stewart are not as solid, and since they are $500, don't do it. Use a monopolar loop and just cut the suture. It cuts better, for reasons I don't understand, but it does, and they don't break as easy. That's the technique to remove them chronically, after three, six months, once they're embedded if you have to do it or you have to do something over.

Dr. Krambeck:

that's perfect. We only have a few minutes left. Dr. Roehrborn, do you have any take home messages that you would like to give the audience?

Dr. Roehrborn:

Well, useful the last 25, 30 years, is start off patient with medication based on their symptom and bother. In general, this is what's going on all over the world. Our patients take it, but then they don't take it. The compliance is poor. They drop of the medication, the medication loses effect, the patients are dissatisfied. There's a bunch of patients out there that are sort of not really doing great, but also not coming back or we don't even know about it.

Dr. Roehrborn:

The second thing is, when we do a surgery, we think this is it. This is the final solution, whether it's TURP or HoLEP or [inaudible 00:51:30] or whatever it is, but it is not always. People have ongoing symptoms, and sometimes, and I like to hint at that, sometimes it's because our best ablative procedures come so late that the bladder is gone, or the patient is already [inaudible 00:51:45] over activity or even under activity, and there is no rescue. It reminds me a little bit of Whitmore's quote, about prostate cancer, it works great if you don't need it, and if you really need it, it doesn't work any longer.

Dr. Roehrborn:

Well, if you wait too long on your HoLEP, TURP, and RASP, it don't work anymore, because the bladder is now the culprit. This was my point about the window of opportunity, so to the audience, and myself, think about these things moving up the intervention a little bit earlier, perhaps, in the disease process, when the patient still can get a great deal of benefit out of that. He still has a really good functioning bladder, and it improves flow, frequency, hesitancy and nocturia, et cetera, et cetera, and think about them as sort of your midfield play, if you like the soccer analogy, between medications and surgery before it comes to the surgery.

Dr. Krambeck:

Excellent. I agree, totally. Dr. Barber, 30 seconds. What do you have for take home?

Dr. Barber:

It's difficult to add much to that, but I think we're an interesting world for patients and for urologists. We have so many different approaches now in terms of relieving bladder [inaudible 00:52:59] structure and [inaudible 00:53:00]. Whatever points in their natural history, the patients come to us, and I completely agree that we need to be trying to act early or encourage action earlier. I think it's a difficult place now when we have so many different options, be it in the circle [inaudible 00:53:16] surgeries, we've got choices. Now, in the minimally invasive surgical treatment field, we have a number of choices and more coming along down the line.

Dr. Barber:

The challenge, I think, for all of us, [inaudible 00:53:26] involved lot of, is trying to identify which patient fits the bill for which treatment, because I don't think they're all the same, and trying to tailor, if you'd like, which procedure for which patient is going to be the challenge going forward.

Dr. Roehrborn:

Dr. Krambeck, one quick [inaudible 00:53:46] for that, the EAU had said that for many years, the AUA finally in 2018 agreed to it in their guidelines, and it was my instigation to it, prostate size, do an ultrasound and have a both a transverse and a [inaudible 00:54:00] image of your prostate. Know the size, know the shape, know the intravesical growth, that will set the stage amongst the myriad of choices what you want to do. Don't give a hundred gram prostate an alpha blocker, and don't set him up necessarily for iTIND, I would say. If you know the size and the shape, you are well ahead in the game deciding what works best for that patient, you avoid a lot of frustration.

Dr. Roehrborn:

That's been for a long time in the EAU guidelines, finally it's in the AUA guidelines, and I think, rightfully so.

Dr. Krambeck:

Well, excellent advice from two expert, world class surgeons, and I really appreciate your inputs today.

Speaker 4:

I just want to thank everyone for their terrific presentation. I learned a lot.

Dr. Krambeck:

I would like to remind everyone, next week we have the robotic radical prostatectomy with Dr. Pruthi and Dr. Singh. I think we should all try to log in here. You will get a survey from Michelle Paoli for your CMA credit, so please fill out the evaluation and the questionnaires.

Dr. Krambeck:

Then, we encourage everyone who is not already a member of the Endourology Society to become a member, and the information to do that is on the website. Finally, please join us in 2021 in Hamburg, Germany on September 21st through the 25th, for the World Congress of Endourology.

Dr. Krambeck:

Thank you all for being with us today, and we will see you next week.

Dr. Krambeck:

If you do get into bleeding during iTIND or UroLift, how would you handle that? Like, what would you do if the prostate started bleeding?

Dr. Barber:

It is difficult. Obviously, one of the big pushes, particularly at the moment, about [inaudible 00:55:44] that's got a lot more history behind it, and has both full badges in terms of NICE, level 1B recommendation evidence wise, and strong recommendation BAU, lots of history now the class didn't touch on, but there's now real world data of 14 hundred patients, which, again mirrors the same kind of output in terms of symptom and flow improvement.

Dr. Barber:

The big key thing it's trying to push itself that's different from Rezum, which obviously has much less data behind it, only one study really, is about performing under local anesthesia, and this is very popular in the States, because [inaudible 00:56:26] do it in the office. Some use various levels of either oral or low level sedation, or nitrous oxide is becoming very popular, I believe.

Dr. Barber:

The key thing is when you get bleeding in that setting, because obviously I do it under sedation, and they're properly sedated, and because we do it with an anesthetist, if you run into trouble, you want to say increase flow, squeeze the bag, just so you can see what you're doing, then you can do that, and it doesn't really matter. If somebody's under local anesthesia, and you start filling your bladder quickly, they're not your friend for very long, in terms of doing that.

Dr. Barber:

Yes, contact bleeding, which is essentially what it is, can be a problem during UroLift, or, if you're unlucky when you fire a device, it pops through a little vessel and it bleeds out of the device. However, they do compress, so even when that happens, it tends to stop, because it's actually compressing the prostate tissue. Rarely, in all the cases that I've done over six or seven years of UroLift, rarely has bleeding ever really become an issue in terms of safe and appropriate placement of the implants, if the truth be known. Has it been a bit tricky on occasion? Yes, but it is rarely a real problem. It's really, then, just about emptying the bladder, getting your flow up, and placing devices safely.

Dr. Barber:

With iTIND, by general experience is much less, of course. The key, as I said, to anything is really about positioning it the first time round. Because if you can keep that view, and position it quickly and smoothly, then you never get to the point where bleeding's a problem.

Dr. Barber:

Mostly, you're dealing with, and again, if you look at the studies, unlike the UroLift data, the reality is the prostates for iTIND are very small, and for me, I'm doing it in a very, very particular group of patients, and that is those with a high, tight bladder neck. Because I think the UroLift struggles in that setting, and you're talking about barely 30 mil prostates and Rezum also I think is inappropriate in that setting, given there's not really any adenoma to treat per se.

Dr. Barber:

That's why I'm interested, I'm trying to put the message to Medi-Tate and Olympus, that for me, they want to go after this unique selling point, this particular group of patients, where I'm not sure for the particular setting, and of course, they don't really bleed very much, and as it pings over the bladder neck, they're positioned very nicely. If you start doing them in bigger prostates with middle lobes, then, yes, you could easily start to get into problems, because the flow is compromised.

Dr. Krambeck:

That's a great answer. There's a whole group of questions that came in about how long you leave the device in place. This five to seven in dwell time, is this based on prior studies? How do we know that that's the right amount of time? Would longer be better? What happens if you just left it there?

Dr. Barber:

Well, I think the key thing with it is, that it is not very, and I try to be up front to the patient, so if he decides to take this up as an option, I mean, it is not a lot of fun when it's in there. There's something pushing out. It is like sitting on a tennis ball. It is painful, but even now, I think we've worked out with medication [inaudible 00:59:44] get that under control with proper analgesic, or in fact you give them a low dose of steroid, which seems to be the real winner in this.

Dr. Barber:

Urgency, as you might expect, this thing's crossing the bladder neck, and essentially setting, to some part of it, on the [inaudible 00:59:56]. Guess what? They've got significant urgency, and although the Italians send them home with anticholinergics, I haven't bothered just because it doesn't seem to make any difference, and of course they come with a lot of side effects.

Dr. Barber:

It's really urgency and discomfort, and then the incisions, I think as I alluded to, I think really seem to take place in the first two or three days, and that's because it's the first two or three days where there's the most discomfort and there's the most hematuria. It's then, the next day or two, is when it all starts to settle itself down, whether that's because they know they're coming along to have it out, and they're just counting down the hours, or whether it's psychosomatic or whether that's really so, I think you can get away with five days. The five to seven, that's been based upon animal modeling. It's never been any different. The Italians, as far as I'm aware, always put it in for that amount of time, and so it's been based upon how many days it takes for the maximum amount of pressure necrosis and the best incisions.

Dr. Krambeck:

I really like the fact that you use steroids. We use it a lot for stonework and BPH as well if they're having dysuria. I think it's highly effective. Do you ever use narcotics?

Dr. Barber:

No, I try to avoid narcotics, you know, partly because of the side effects. Again, the last thing you want is these people getting constipated on top of everything else. That just would be disastrous, I think, really. No, I tend to stick with just non-steroidals and paracetamol, basically, maybe with a bit of codeine.

Dr. Barber:

It's the steroids what's like a magic wand. When I started off, when I was doing the trial [inaudible 01:01:40] so horrible, that I swore I'd never do it again, and that was about three or four years ago, and it's only I sort of revisited it by going to [inaudible 01:01:50] and seeing how they manage their patients, because they were telling me it didn't hurt, people didn't complain of pain, and I was like, whoa, my patients suffered. The magic wand was the steroid as you say. I don't think we maybe as urologists we don't think about steroids enough in many settings, but it seems to be the big difference.

Dr. Krambeck:

That's great. Another question-

Dr. Roehrborn:

One question, what dose did you steroid?

Dr. Barber:

oh, 10 milligrams. 10 milligrams.

Dr. Roehrborn:

10 milligrams.

Dr. Barber:

Yeah. Correct. Tiny, really. Of course, they feel great as well. That's the other thing.

Dr. Krambeck:

That is the thing.

Dr. Barber:

Everybody loves the steroid for a few days.

Dr. Krambeck:

Having personally taken steroids for a few days, I do like them.

Dr. Barber:

Yeah, yeah, yeah. [inaudible 01:02:41]

Dr. Krambeck:

Another question that came through, has the company talked about a tipless device which would make it be easier to put in a catheter if the patient is unable to urinate.

Dr. Barber:

No. I mean, I think the twines, there is a shape to this thing, like a basket if you'd like, so it's got to have a beginning and an end. It's not the tip that's in bladder it's the problem, it's getting through the sphincter basically, and you've got the device that sits gently across it. Nobody's asked, I don't think, about the risk of being [inaudible 01:03:13], so that's always the thing that scared me. You got these struts pushing out pressure in this prostate of variable length, what about through the sphincter? It actually, all the pressure really is at the distal end. It's at the bladder neck. This is why for me, this is a bladder neck incision device, essentially, and it doesn't seem to be very much pressure, and you can see from that video that that's where it has its effect, and even a short prostate, as you move back towards the apex, you don't see much evidence of what's going on really. It's really at the bladder neck.

Dr. Krambeck:

Okay. That makes total sense. Another question, and I think I know how you're going to answer this, but I'm not sure. You use a 19 French scope for this, and one of the questions that came in is have you ever thought of using a wider cystoscope, like a 22 or 24 French scope, or even a nephroscope, so that you can watch the placement under direct vision the entire procedure.

Dr. Barber:

Well, I use a 22.5. I just use [inaudible 01:04:17] Olympus, so I think the [inaudible 01:04:21] minimum, to fit the device with the sheath down. Anything smaller than 19, you won't be able to get the device in, so that's what that is, it's a minimum of 19, rather than the maximum.

Dr. Krambeck:

Okay.

Dr. Barber:

If you're going to use a rigid scope, there is a limit in terms of the amount of space as you pass through the prostate at the neck of the bladder, so the bigger it is, the more difficult in fact it is to wiggle things around, and withdraw your cystoscope to just within the bladder neck within the prostate and be able to manipulate the device separately. Otherwise, it's just jammed. It all jams together and you can't see that vision. You can see in that video, I had to play around a bit, just to bring it back because you do want to be in position to see the tongue come over. Because once the tongue's come over the neck, it slips down to position. You saw it exactly as it happens in the video, drop down, you're out. That is it.

Dr. Barber:

If you go bigger, I suspect you'll find it harder. In fact, you want to go down as small as [inaudible 01:05:15]. If you had a 19, then that would be great. We use a [inaudible 01:05:18] 21, 22, sorry, and that's what I have.

Dr. Barber:

There is being thoughts about using a flexible cystoscope to place this, so that once the device, and you could use something a bit like a access sheath to place the device into the bladder then go down alongside the guide wire with a flexible scope. Because all you want to do is see it so you can rotate it and position it. Yeah, so, flexibles have certainly been used as well, and then you can look through it and all sorts of things if you want to, because it is that much smaller.

Dr. Krambeck:

This is a case where bigger is not always better, right?

Dr. Barber:

Exactly. Exactly.

Dr. Krambeck:

Then-

Dr. Barber:

No comment on that.

Dr. Krambeck:

This is a UroLift question, so what if you have a patient who has a penile prosthesis. Would you still go ahead and place a UroLift? Is that an issue or does it preclude you from doing the procedure?

Dr. Barber:

I can't see why it would.

Dr. Krambeck:

Okay.

Dr. Barber:

I have to say, [inaudible 01:06:25].

Dr. Krambeck:

I think maybe that's more of an issue for more resective surgeries, where we use a bigger scope, so you sometimes cannot get the scope in, but with the smaller size scopes that's being used for the UroLift and the iTIND, I think it shouldn't preclude the procedure.

Dr. Krambeck:

Then, which degree telescope do you use for each procedure? UroLift as well as iTIND?

Dr. Barber:

Just because I have a 12, for the iTIND placement, just to say, it's just under whatever your normal cystoscope is, so we tend to have a 12 for that, and it's a zero for the UroLift.

Dr. Krambeck:

Okay, so zero for the UroLift. Is that so that you can get that angulation in, and you know exactly where you're putting it.

Dr. Barber:

Yeah.

Dr. Krambeck:

Okay. Then, everybody's asked the max prostate size. It sounds like really, you don't want to be going above 80 grams for these cases.

Dr. Barber:

Well, certainly, yeah, I think for me, and Francesco Porpiglia disagrees with me completely, and he has more experience. He thinks the sweet spot for iTIND is sort of 30 to 50 odd mils. I think it's high bladder necks, 30, whatever they come in at, 25, 30, 35 mils. Certainly, the randomized trial that we're talking about, which would be MTO8, I think it's called, in Europe, will be under 40 gram prostates versus iTIND, and I think they're right to go down that line.

Dr. Barber:

UroLift, as you say, has data and all the badges for up to 80 mils everywhere, and then 100 mils with the FDA. I think most people who are honest will look at any of these minimally invasive surgical treatments and the main players being UroLift and Rezum, and say that as you get bigger, you start to lose two things. One is predictability of effect, and longevity. I think, even as somebody who's been involved with these a long time, I'm very comfortable telling people that, yeah, sure you can have it, but I will be concerned about the predictability of effect and longevity compared to a 40. For me, a UroLift sweet spot is 40 to 60, 70 mils.

Dr. Barber:

It is sometimes, you'd have a bigger prostate, and they just respond amazingly. I mean, it's just incredible, you go, "Oh, my gosh, that's amazing." But it is not as predictable, and I do get worried as you cruise towards the 80 mil plus range.

Dr. Krambeck:

Well, and I think that is probably the best take home message from this production, is, you need to tailor the treatment to the patient. If they have a smaller prostate, they're probably not the best candidate for an enucleation or resection and they do better with one of these procedures. Then, if they have a bigger prostate, you'd be better off using a more aggressive approach.

Dr. Krambeck:

I'm going to finish off with one last question. This is about prostate cancer. Men with a locally advanced prostate cancer can end up with obstruction. Has there been any consideration the using iTIND or UroLift in these situations just to deobstruct them?

Dr. Barber:

Certainly, I mean, iTIND [inaudible 01:09:33] and that's a baby in all this, so I have no idea. I suspect not. UroLift, not to my knowledge in untreated, locally advanced prostate cancer, have I come across that. I've seen a few patients over the years who are post-radiotherapy, and instinctively you would think that they would do very badly, because you would think their tissues are not so compressible, but actually the handful that I've done responded surprisingly well.

Dr. Barber:

We were in the throes of trying to set up a randomized trial for brachytherapy patients, so those who are obstructed with smaller prostates before brachytherapy because of all the risks that go with that in terms of post treatment surgery. I was quite interested in that, and where the UroLift might have two roles, one is relieving obstruction, allowing them to get on with the treatment quickly, rather than having a mini TURP type thing, which is quite commonly done, and then having to wait a number of weeks while things settle down before they have their brachytherapy, so whether that might be able to speed the process along, relieve the obstruction sufficiently, but allow them to get on with their treatment quickly as well. I'm not aware that's ever turned anywhere into fruition in terms of a pre-radiation treatment.

Dr. Barber:

There was talk of a trial in the States of post-radiation, so an external being, prostate cancer and UroLift, but I'm not aware of if that has progressed.

Dr. Krambeck:

Okay. Well, maybe we'll see that down the road, and see what role it plays.

Dr. Barber:

I'll just say, I think the key thing, beyond trying to identify the tailoring aspect of all these different procedures, but is also what Klaus Roehrborn referred to is that this started to think about how these devices fill the space. They're not so much necessarily always just an alternative to surgery, they're alternative and a more aggressive alternative to medication. Really, starting to ask should we be pushing a bit harder in terms of men's initial presentation and how they're treated, because the pharmas have been laid in stone in all our guidelines since the late 90s. Step one, alpha blocker, step two, you know, and then they disappear off.

Dr. Barber:

Certainly, in the UK, through guidelines, the power of that is in the primary care physician, so we don't even know about it. We don't even get an opportunity to have that conversation, so how do we change that, because it may be, how do we take that 60-year-old with detrusor failure? What happened to him? Could intervention 15, 20 years earlier have changed where he's at, because he's stuffed, and do we have the ability to change that.

Dr. Barber:

I don't think we really know the answer to that, but, certainly, these devices have started that debate and conversation happening. That's really important.

Dr. Krambeck:

I think that is an excellent point, and it is unusual that we do this step-wise with medication, because there's quite a few side effects to the medication. Especially the 5 alpha reductase inhibitors, we're seeing quite a few significant side effects with that.

Dr. Barber:

Yeah. I'd love to see one of these devices randomized. They need to be done about the standard of care, and I'm very upset that Boston have dumped it and will not be doing a randomized standard of care because they've got away without doing it, but somebody needs to do it against medication, because we don't really have any clean data on the side effects and tolerability of medication. We rely on pharma sponsored trials from the 90s, that data.

Dr. Krambeck:

Yes. You're one hundred percent correct. All right. Well, thank you again.

Dr. Barber:

Pleasure, pleasure.

Dr. Krambeck:

It was a wonderful presentation.