Christian Gratzke: Well, thank you very much for having me. It's a great honor, and it's also great to present this trial, which is called, as you said, the WATER III trial. So we compared aquablation versus any transurethral laser enucleation, whether it was thulium or holmium enlarged prostates. I'll present to you also parts of the 12-months data. If you are interested and would like to read up the 3-months data, they're available here in the publication in European Urology Focus, which by the way today received its factor of 6.3.
So here are my disclosures, and this is the study design. It's an IIT and ICT with three German sites and two sites in the UK. For quality assurance, we required that each individual surgeon had to do at least 30 procedures. The primary efficacy at 3 months was the change in IPSS and safety was based on Clavien-Dindo. Secondary five years we will report in the following years.
We included patients that had an IPSS of at least 8 and a large prostate, but we also excluded patients that were under anticoagulation, that had a very large BMI, prior prostate surgery, a history of strictures or bladder neck stenosis, and suspected prostate or bladder cancer. We ended up treating 98 patients and 88 patients in each group respectively.
Here are the demographics', baseline parameters. As you can tell, those were very similar. The only difference was the age, 65 versus 67 years old. But prostate size was on average, 108. Intravesical protrusion, 74 and 82%. IPSS around 20, 21. Catheter dependent were around 19 and 24% of the patients. Qmax around 11. PVR, 101 and 110 respectively. The procedure duration might be interesting. It was 58 minutes for aquablation and 61 minutes on average for the laser enucleation.
I'll jump to the prostate volume reduction as primary analysis as you can tell here. When you look at prostate volume reduction, laser enucleation is significantly more effective than aquablation at 3 months. If you look at the IPSS improvement at 12 months, you can tell that there's no significant difference. The improvement was around 15 points in each group respectively.
Looking at the functional outcomes here, PVR on the left side and Qmax on the right side, as you can tell here as depicted in red again for enucleation and blue for aquablation, the functional results were significantly better for laser enucleation of the prostate versus aquablation at 12 months. And the same result was shown for Qmax improvement also at 12 months.
On the other hand, if you look at results for safety and other functional results, looking at bleeding risk, UTI risk, sexual function, urinary incontinence, first maybe look at the upper left panel looking at bleeding risk. We did take a few more patients back to the OR after aquablation, which was significant, but there was, in absolute numbers, a very low rate of patients that needed it.
UTI risk was the same. Ejaculation disorders, significantly better in the aquablation arm in comparison to the enucleation arm, 14 versus 77%. And I think that's really important to show that no erectile dysfunction was shown in either group.
Looking at urinary incontinence, and this is to be clear, the 3 months results, you can tell that any urinary incontinence was higher for the laser enucleation arm.
I'll come back to the incontinence now. This is the de novo PET use of at least one PET. That's a very strict definition, but we though if you use one PET or more that you didn't use before, then that should be considered being incontinence. And if you use that very strict criteria, you see that we had more patients with laser enucleation that were suffering from incontinence at 3 months and at 6 months. However, the numbers went down from 3 to 6 months and we expect them to go down at 12 months, but we have not looked at these results yet. Again, in absolute numbers, very few patients, three patients stress incontinence and one patient for urge and mixed incontinence. Looking at re-intervention rates, urethrotomy for laser enucleation patients in two patients, and we had to take four patients back to the OR when they had had aquablation in the upcoming 12 months because of remaining prosthetic tissue.
So in conclusion, I think it's fair to say, and maybe it's not a big surprise for all of you who are experts in that field, that for symptom reduction and PVR reduction, there's no difference between aquablation and laser enucleation of the prostate. When it comes to prostate volume reduction and Qmax improvement, enucleation is superior to aquablation. If you're specifically interested in enucleation preservation and stress urinary incontinence, aquablation is superior to laser enucleation of the prostate. And it turned out that the stricture rate was higher for enucleation, but the re-treatment rate was higher for aquablation. Thank you very much for your interest.
Alan Wein: Terrific summary. That's going to be really attractive to consult for actually a number of people. So the higher stricture rate, even though it wasn't terribly higher, is that just related to the amount of manipulation you think that you have to do with the scope doing a HoLEP rather than an aquablation?
Christian Gratzke: That's at least what we think. I completely agree with you here. The absolute numbers are low, and there has been a lot of discussion around the stricture rate for any kinds of laser enucleation, whether it was holmium or thulium. Any cohort that you're looking at is anywhere between 2 and 8%. It's very interesting. If you look further, you see the novices. Usually, they tend to have a higher stricture rate, and we think that's because of more movements in the urethra. We did observations and trials where we looked at how many times the surgeons went in and out during the enucleation. And I think that's what causes the stricture rate, but that's still a hypothesis, which I have not proven.
Alan Wein: Was there any apparent difference between the two types of lasers, holmium and thulium at all? Did you have enough to look at that?
Christian Gratzke: Great question. We did. There was no significant difference, no.
Alan Wein: So pretty much the same?
Christian Gratzke: Yes.
Alan Wein: And having done this, and obviously having treated a lot of patients or been involved with a lot of patients that have had both types of treatment, suppose you had a patient with a middle lobe, do you think one is superior to another or not?
Christian Gratzke: We did look at that, and it turned out that there was no difference. I would've thought if you had asked me before, that enucleation was better for them, but that was not the case. So in all fairness, both techniques are a good instrument if you have a patient with intravesicle protrusion. So we measured how far that middle lobe intruded or protruded to the bladder. And you saw the numbers at the beginning, but both procedures were similarly effective in those patients.
Alan Wein: And as far as the incontinence rate, you're waiting for the 12-month figures for that?
Christian Gratzke: So what we saw and what was very reassuring was that the rates were going down from 3 to 6 months. We had very few patients that were still suffering from incontinence at 6 months, so we expect them to go down further and we hope to have no patient at all at 12 months. We know from large series around the world that incontinence rates really usually resolve at 12 months.
Of course, I may have to add that these were all experienced surgeons. Most surgeons had had three digit numbers in operations before, and we know that there is a very hard learning curve for any kind of enucleation. So we expect them to have very little incontinence. But of course, everyone that's doing a lot of those surgeries knows that in these patients, there are many co-founders that lead to incontinence. It's hard to direct that to the surgery itself always because when you go back and somebody is suffering from incontinence, there's hardly ever any damage to the sphincter.
So there's also here in this trial, no correlation with the treatment duration, which I think it is. If you take a very long time, the longer you operate, the more incontinence you will have. But yeah, so in summary, I think a low rate, but still more in the enucleation group in comparison to aquablation.
Alan Wein: For the amount of prostate tissue remaining, those were the estimated grams on... How was that measured? On an MRI or on an ultrsound?
Christian Gratzke: That was an ultrasound. We did not do an MRI.
Alan Wein: It was ultrasound?
Christian Gratzke: Yeah.
Alan Wein: So in other words, it looked as though percent-wise that the one was about, it was 25% more prostate tissue resected than the other.
Christian Gratzke: Correct.
Alan Wein: In other words, that the HoLEP really took out more of the prostate. I was always amazed doing TURs on the occasions when we had to go back for some reason and do an MRI on those patients how much prostate tissue I left behind, even though I thought I did a great job.
Christian Gratzke: I very much agree. And I think maybe it's also we could discuss how much volume you will have to reduce in order to get a good result, right?
Alan Wein: Right.
Christian Gratzke: Because you're amazed how little you have to take away in order that the patient is happy. It may have to do with durability of the treatment. And of course, we know that for enucleation in an experienced surgeon, you roughly remove around 70 to 80% of the tissue, which was the case here. And it's obviously less for aquablation. Whether this is necessary, nobody knows. We have those, maybe what we call, this is short-term. We do have 3 and 5-year results for aquablation as well. But if you look at 10, 15 years down the road, that's a different story.
Alan Wein: Yeah, it'll be very interesting to see what the numbers look like when the follow-up is that long for both types of procedures.
Well, that was really terrific. I think a lot of people are going to benefit from taking a look at this study, taking a look at the slides, the PowerPoint that you put together, because I think it's really going to clarify the situation for a number of people. So we really thank you so much for your time. I know it's an inconvenient time over there now, and so we especially thank you for interrupting your day and early evening to be with us. But listen, thanks very much and I hope to see you at another meeting really soon.
Christian Gratzke: It was my honor. Thank you very much for having me.