Jeremy Teoh: All right. So thank you, Sam, for the kind introduction. My pleasure to be here talking about a topic that is very close to my heart. And in particular, I will focus on a novel robotic system designed to have a high quality bladder tumor resection.
So my team at the Chinese University of Hong Kong, and I myself conducted the first-in-human trial using the Virtuoso Endoscopy System, but I do not have any financial conflict with the company. So conventional resection is performed by resect tumor kind of in a fragmented manner, but we have always wanted to improve the surgical quality by doing an en bloc resection, trying to avoid tumor fermentation and reduce the chance of implantation. But in my opinion, more importantly is to ensure a complete tumor resection, not only judged by the surgeon's eyes, but also by proper histological assessment of the resection margins.
And certainly there are many ways of doing it, but one of the criticisms is how we can generalize the procedure more easily, making sure that every surgeon can do it in a very high quality manner. And that's how we performed the first-in-human trial using this very interesting robotic system, which essentially has to be very small, because the urethra is small. So the system makes use of a cystoscope, which is about 26 French in size. But more importantly, will be the two instrument arms, roughly around 1 millimeter in size, and hence enable a two-handed approach in performing the resection.
As you show a robotic system, we have a console on the left there. So a surgeon can use both hands in controlling the two arms. On the right would be the cystoscope, but also a balanced cart, making sure that everything is stable. So basically, you yourself or assistant can help move the system. But very interestingly, you can also rotate the whole system, both camera and also two instrument arms 180 degree, depending on the location of the tumor. And you can naturally apply your previous laparoscopic robotic experience, and then basically perform a two-handed resection during the whole procedure.
So last year we did the first phase of the VIABLE trial, which is the first in human trial. We have included 6 patients with 12 tumors. I think the best way is to really show you the field of the whole procedure so that you have a good idea about the system and how we performed the procedure.
So this is actually, well, number one case. We basically make use of two arms here, left arm is a retractor, and then on the right arm is the two limb fiber laser. And naturally, you would try to use the laser to have a sharp incision. You would use the left arm to lift it up so you create certain kind of tension as you try to perform the incision. And also naturally, because you have previous laparoscopic experience, so when you're trying to define the anatomy and specifically where the submucosal tissue is and also where the detrusor muscle is, then you would also apply some kind of blunt dissection along the way. So you can really try to find where the junction is. Ideally, you remove everything above the muscle layer, but also get a bit of muscle for the staging purpose.
And as a first in human case, of course, we would spend some time in training and learning. We spend some time in docking a system, et cetera. But the actual resection time for this case, I think it was about 15 minutes. And I think it's quite easy to adopt and also quite easy to use as well. And also there are a lot of tips and tricks in order to make the system happen. Because the instrument is so small, you can see we're having some kind of crossing maneuver right here. Generally, it's not easy to happen when you have a bulky system, but because the system is... The instrument arms are so small and the way that the robot is being designed allows this kind of precise, small movement without any significant clashing.
And in our first six cases, we basically have done tumors located pretty much everywhere, near the bladder neck, near the ureteral orifice, near the bladder dome, and we did not experience any issue. So I'm glad to report that. I think it's very easy to adopt, safe and technically feasible.
So 12 tumors, mean over time of 15 minutes, but as mentioned, there's a learning curve there. Technical success rate 100%. In all cases, we're able to obtain detrusor muscle. Interestingly, 5 were Ta disease or the resection margins were clear, but then one patient came back to be an early T2 disease, but I must say endoscopically, the muscle layer looks very healthy. So we decided for a second surgery, which was negative, and eventually pursued a bladder-sparing approach for that particular patient. And there's no grade 2 above complications.
As Sam has mentioned, I've done quite a lot of work on en bloc resection. First introduced back in 1980, popularized in Europe back in 2015, but in the past 10 years, we have done a lot in terms of establishing the consensus statement. We conducted the first randomized trial proving that it can improve the recurrence rate one year. We had a phase-2 trial modified en bloc for large tumors. We have an IPD meta-analyses proving whether en bloc resection has a genuine benefit over conventional resection. We also have a registry of over 3,500 patients right now, further defining the best management alongside en bloc resection. And now we also have a robotic system. So I think now has become a very exciting area, and I hope more surgeons would be committed in performing a better quality surgery for our bladder cancer patients.
But I think en bloc resection is really just the beginning, because with this system, basically we can have different ideas and explore new ways of treating urological diseases. So suturing obviously is something very interesting. It's still being underdeveloped in the laboratory, but I'm quite confident that it will still happen. So after the initial trial, probably we explore its feasibility in other urological diseases or procedures in the future.
So for example, whether we can do partial cystectomy, whether we can actually perform some kind of distal ureteric surgery, lack of excision or even diverticulectomy. I think it's really up to us to explore new and better ways in treating different conditions.
So in summary, I think en bloc resection, in my opinion, is a better way in treating non-muscle-invasive bladder cancer. Certainly, urologists have played an important role in robotic field from multi-port, to single port or even from transperitonial, [inaudible 00:08:20] sparing, transfer cycle. We've proven to be the real innovators in robotic field, but certainly we look forward to using the transurethral system. It's going to be the next breakthrough, in my opinion, and an exciting journey, exploring new and better ways in treating diseases. And this is really what true innovation is about because it's about being disruptive, being novel, but at the same time, it's up to us to really find out the real clinical value to our patients. And we certainly look forward to it. So I must also thank my team because without them, this will never happen. So thank you, and I look forward to our discussion.
Sam Chang: Jeremy, thanks so much. I mean, to go from within a very short period of time of, yeah, we're starting this en bloc technique, and where you've taken that from initial attempts a few decades ago, really not much kind of traction. And now, I would suffice it to say that the vast majority of urologic surgeons have now at least heard of it. Understand it's not only theoretical benefits, but clearly your randomized control trial actually showed a decrease in recurrence rates using an en bloc technique. Obviously, it was in smaller tumors and carefully studied, but really shows some oncologic benefits.
So let's start with in general en bloc surgery. Tell me, for the practicing urologist that maybe not have access to the robot, because we'll talk about the robot, tell me some initial tips that you would tell urologists. Avoid obviously, big bulky tumors, et cetera. But if someone wants to start initiating this kind of technique, tell me some initial tricks that you would pass on to them.
Jeremy Teoh: So first of all, you choose your energy modality. androgen bipolar is very sharp and precise, but you need to learn your hand movement, how you rotate your wrists, your hands in order to have the best incision, but also at the same time to protect the specimen.
The other modality is obvious different kinds of laser, which is very good as well, very sharp in terms of incision. But then two things, laser, it's end-firing. So if you are dealing with bladder dome tumors, it's more difficult because it's end-firing, so you tend to get deeper and deeper. So choose posterior, lateral or anterior tumors to begin with, it will be better for laser. And also in terms of laser, unlike end resection loop where you can push the tumor with a blunt dissection, whereas using laser is a little more difficult. So after the incision, you need to get nearer, under the flap of tissue so that the scope is kind of lifting up the tumor, but at the same time, you have enough space to use the laser to incise further. So it's kind of a very precise surgery, whatever energy modality they use. But I guess to begin with, always find somebody who has experience to provide some mentorship will help a lot.
Sam Chang: So tell me now your go-to for larger tumors in terms of extraction. Are you using a larger instrument? Are you using a smaller Endo Catch bag? How are you removing larger tumors now at this point?
Jeremy Teoh: So there are a few ways of doing it. Some would advocate using Endo Bags. Some would use a small laparoscopic forceps through the morcellator telescope because the channel is wider there. Some would perform modified en bloc because as we do more procedures, we realize that, at least in my opinion, having a uniform high quality resection at a base, especially for large tumors, is probably arguably more important than whether you're removing one piece or three pieces, for example.
So modified en bloc is basically trying to do it as en bloc as reasonably achievable so we can potentially debulk the tumor, the exophytic part, but perform en bloc resection of the base, for example. Or you can preplan en bloc in three pieces, for example. And in fact, I haven't talked about it in this presentation, but we did a phase-2 trial. 30 patients just on patients with bladder tumors larger than 3 centimeter. We did preoperative MRI scan. We performed modified en bloc. We performed post en bloc MRI scan. For those with non-muscle-invasive disease, then we proceeded with [inaudible 00:13:01] surgery. Muscle invasive disease, then we advise for cystectomy, it is a localized disease.
So basically we found that for non-muscle-invasive tumor, we're able to achieve a negative second [inaudible 00:13:13] surgery in over 90% of patients. And bearing in mind, these are patients with very large tumor, very challenging tumors. And for those with muscle-invasive disease, proper staging is again over 90%. And interestingly, for those with T2 disease, actually up to 75% had a pT node disease upon cystectomy, which is fairly high compared to what has been reported in literature.
So I think the bottom line is no matter what you do, I think quality matters. It matters certainly for large non-muscle-invasive tumor, but even for muscle invasive disease, especially when we are probably towards bladder-sparing approach with those novel agents, with ctDNA, et cetera, I think our role in terms of endoscopic resection will grow bigger. So definitely as a urologist, we need to perfect that as well.
Sam Chang: Yeah, that's a perfect segue. Clearly, the newer systemic agents really have shown a significant response, not only for advanced and metastatic disease, but perhaps for disease still localized in the bladder. But then that leads to, okay, what are we going to do to try to bladder spare? And now you've got a robotic technique that is less invasive, that provides an accurate pathologic specimen. So where next with this robotic platform? Tell me your thoughts regarding, okay, how we're doing with enrollment, where our next study is? Tell me the next steps in the future with this robotic platform.
Jeremy Teoh: So right now we have performed actually 10 cases so far. We plan for another 10 cases in April, and then another 10 cases in May and June. So we're really trying very hard to have-
Sam Chang: Yeah, absolutely. Absolutely.
Jeremy Teoh: Yeah. And hopefully, this will speed up the approval process. And I think we are confident that we will be able to achieve that in Q4 this year or Q1 next year. That's our goal.
But again, this is just for bladder tumor excision. Of course, we need to discuss on the next step, but in my opinion, I think en bloc is just the first step. What I really look forward is really how we can use the system to do something or achieve something that can never be done before.
Sam Chang: That last slide with all the possibilities of the benign areas, the bladder ticks, the re-implants, I could even think of other possible applications. And then you throw in, what about an adeno CA, which doesn't have a chance to basically... Partial cystectomy is perfect for that. All these possibilities with the ability to suture is amazing. So having that ability and understanding the effectiveness of single-port and robotic transperitoneal and within the retroperitoneal space, this is actually without any incisions. This is the true, natural orifice and then being able to actually utilize that. So where do you think then, Jeremy, would you go next in terms of that next step? Which population of patients?
Jeremy Teoh: Well, I think certainly at the beginning we'll still be bladder focused, because that's how the platform is being designed. So certainly, solitary T2 muscle invasive disease, these would be the best cases to perform partial cystectomy. But of course we need to plan ahead, good preoperative assessment. And then even whether we should use normal saline or [inaudible 00:17:00] in doing the surgery, suturing, et cetera. We need to plan for it.
Diverticulum makes a lot of sense to me because really there's no reason why we need to go through the abdomen anymore. Distal ureteric surgery, I think makes a lot of sense as well. So I think these are the few areas that I really want to do, and I think it will really make a real impact on these patients as well.
But at the same time, would love to have your insights, expertise, because we need urologists to be involved. We need to know and explore things together. And this is one of the rare opportunities that we have a good system, and it's up to us really to find out the real value. So we look forward to working with different urologists over the world as well.
Sam Chang: No, that's fantastic. Like I said, as I started, the entire field of not only urologic surgery, but surgery in general really is indebted to you and your attempts to take the next step, to realize that innovation is actually the only way that we can lead to further improvements and further next steps. And so, it's a big lift. And the pioneers are always the ones that have the biggest lifts. And so, really I consider you a true pioneer and look forward to your next steps and look forward to seeing where we go next with this robotic platform. So look forward to it.
I know you've got AUA plenary talks, presentations at the EAU. You've got lots on your plate and we look forward to hearing from you and hopefully we'll be able to touch base with you again on Uro Today. And look forward to seeing you again personally as well.
Jeremy Teoh: Thank you very much, Sam. Appreciate it.