Alicia Morgans: Hi, I'm so excited to be at AUA 2022 talking now with Dr. Arnulf Stenzl. Thank you so much for speaking with me today.

Arnulf Stenzl: Thanks Alicia for the invitation.

Alicia Morgans: Oh, of course. So I wanted to speak with you about the masterclass that you presented. Which was a masterclass that is sort of a joint collaboration between the International Bladder Cancer Group and the AUA, where really there's a whole day of focus on bladder cancer at this meeting. So can you tell us a little bit about your session on the optimal approach to TURBT?

Arnulf Stenzl: Yeah! I think, first of all, it's a unique session, because it has short contributions where those Pro-Con or where two people look at the same topic. Now, my topic is Transurethral Resection of the bladder. Of course, you could always think that is an old thing. Is there anything new or is there anything useful for that? But actually, this is the first diagnostic step in bladder cancer. And as we have seen, it's first of all important that the first step is done properly and precisely. Because with a precise, good transurethral resection, then the chance for the patients to have a recurrence, and I will show in a minute, we'll talk about progression even, is high. And so therefore there's more to it than just a procedure at the end of the day or in between two larger procedures.

Alicia Morgans: I would absolutely agree. And one of the focuses, at least that medical oncologists are so fixated on, is making sure that there's muscle in that specimen. Which I'm sure is just a piece of what you're trying to do. What are some of the most important aspects of this procedure?

Arnulf Stenzl: Well, one of the important aspects is, you do not always see a tumor that is in situ or in the mucosa. If it's papillary or if it's solid, then you can usually see it nicely. Solid tumors may be problems sometimes. But the carcinoma in situ is a problem and it is a more aggressive tumor than the papillary tumor in most of the cases. So visualization with the eye is not enough. You need additional, a perfectioning visualization, and a perfecting visualization means you try to, for example, use photodynamic diagnosis, which over many years has shown that it can show more than the normal white light, which you see with your naked eye. And the other thing is, of course, you can always try with filtered light, the NBI, the narrow band imaging, or the spies, or the possibility to filter certain colors out of the thing, then to get a better vision of tumor or suspicious tumorous areas.

And I did show that, for example, not in every case, but there is more cases where there is carcinomas in situ, around a papillary tumor. So you remove the papillary tumor, but you're not aware of the fact that you're leaving areas around, which have carcinoma in situ, which are even more aggressive. And on the other hand, you think there is no carcinoma in situ and there is no need to do any adjuvant or additional treatment. So the perfect delineation of the tumor is an important aspect. The other thing is that apart from the delineation, the way you remove the tumor, and you already said about the Detrusor Muscle. There must be Detrusor Muscle in there, otherwise, it's not a valid or a good TURB, which is partially right, but not in all cases.

A bigger problem is that if you do a transurethral resection of a larger tumor, you cut the tumor in pieces and then rinse it out. Can you imagine you would do the [inaudible] Cut it in pieces and then take it out? Because there's a much larger chance of spilling. There's a larger chance of not really realizing whether there is a positive margin or not. Whether it is deep enough and you may then avoid a second [inaudible] as most of the guidelines nowadays say.

Alicia Morgans: So when you're doing that, how do you do that? How do you avoid cutting the larger tumors into pieces, when you're trying to do this properly?

Arnulf Stenzl: We did a study and have looked in a prospective randomized study, at a technique of lifting a tumor with water injection from the normal underlying parts of the bladder wall. And that allows us not only to elegantly delineate the tumor without a positive margin, but it also allows us to give a large tumor, give the pathologist a chance in a large tumor to see whether the margins are positive or not because that is important. Then the third thing is, of course, you don't piecemeal the tumor and then get the chunks out, which is of course we have done it for years and it may be okay on the less aggressive tumors, in the low-risk tumors. But you don't always know what is a low-risk tumor by vision or by macroscopic view. And then there may be both lower risk and intermediate or high risk tumor in the same tumor formation. And you may miss that.

And we have shown that what I talked about it is a surrogate for a better transurethral remove of the tumor. Now the surrogate shows us that, not in every patient but some patients do have a benefit by having a better resection, by using a better delineation, by doing en bloc resection or doing a more meaningful way of resection to know whether there is a positive margin. And these patients not only will have a lower interval until the next tumor more occurs, but they will have an effect that can last four to five years, which cannot be explained with residual tumor. There must be an immunogenic factor with a better resection or it may be that harboring of some tumor cells that these cause at a later stage, not seen or not detected to have a worse outcome for the patient.

It goes even further. We have looked unfortunately not in a prospective analysis series, but we have looked at the outcome of patients with regards to which undergo cystectomy and how do they fade after cystectomy. It seems the better the primary tumor resection, the better the outcome of the patients in the long term. Even if they have to have a cystectomy. The prospective randomized study, which we have done showing the effect of PDD on first, not on progression, but on recurrence. We looked at these series four and a half years later, and four and a half years later there was still a significant lower amount of recurrences. And there was a tendency that less patients had a cystectomy if they had a primary photodynamic diagnostic based TURB. So there's more to TURB.

Alicia Morgans: I would certainly agree with that. And certainly, these photodynamic approaches are so important. What would you say to folks who are saying that, which agents should they use? How do they really integrate this into their practice? Because I think some of the approaches require certain equipment and it's a whole thing to sort of engage.

Arnulf Stenzl: Right? Yeah, yeah, absolutely. You're absolutely right. It's additional cost, it's additional expenditure of course. It depends on by countries, whether they're reimburse the photodynamic effect or the photodynamic based TURB. In Germany they do, and so it's covered by the insurance. But we have definitely shown that these patients have a lower incidence of recurrences after nine months, after four years and more. And so it's, one should explain the patient that he has a lower chance of having a second or third TURB. And if you look at, and I've shown that these data in Europe, we have 300,000 TURB's per year out of 1 million cystoscopies. And the one third is the primary TUR, rest is secondary TUR.

Alicia Morgans: Wow.

Arnulf Stenzl: So that is the majority of TUR's which we are doing is recurrences. So that makes bladder cancer one of the most expensive tumor. Fortunately, the patient live long, but unfortunately, they have a lot of recurrences and sometimes even progression. So by doing a primary best or optimal TURBT you can save the patient from, sometimes you can save him from a second TUR or you can prolong the time until the second TURBT occurs. And there's a lower chance of having a cystectomy.

Alicia Morgans: So what I hear and what I think has really been the message in the community of bladder cancer treatment is that yes, there may be expense. Yes, there may be a learning curve. Yes, there may be specialized equipment, but it's worth this investment because it makes such a difference in patient outcomes. Both in terms of disease control, but also prolonged time to recurrence. And this is really something that our patients deserve.

Arnulf Stenzl: Absolutely, and you formulated it very well. That should be our aim. But of course, we are not perfect right now and there is... We are doing, and we have a major project now going on by intraoperative tumor detection, realtime tumor detection, without having it to do a frozen section. So we have a real-time, better depiction of a tumor, which can be go beyond the photodynamic effect or the filtering light NBI. The difference between is, with a photodynamic diagnosis you get an enzymatic effect or an enzymatic deficiency and which shows you better the difference between a tumor cell and a normal cell by filtering the light, you get structural differences, but you cannot really tell whether this tumor, whether this is a tumor cell due to a deficiency of an enzyme. So that's the difference.

But there is more, we don't want to look at the surface only. We want to look into the depths, optical coherence tomography. There are other optical sensors, there are other mechanical sensors. You can look at the elasticity, not only of the normal tissue like you would do in ultrasound, but by microscopically depressing the area which you think is suspicious with a hydro jet, with a hydro pressure measurement. And then you can also look at the electrical defenses, when we have a bipolar like thing then of which we use for coagulation. But this also gives us some electric data, which then also show which after validation, is this something where we are having less resistance, more fluid, more cells, or is it more tissue? And there is Raman spectroscopy, a hundred years ago Raman did won his noble prize. But even now we find new possibilities, applications of seeing the wavelengths of cells that are different, not only between benign and malignant but also between mucosal cell and a, for example, fibrocystic cell or muscle cell.

So we are getting much, much more information and we can try to do this by combining all these sensory possibilities into a score. Of course, that's a big project because you have to have a lot of data and you have to put these data together and validate them. But we have a very good group together, which then with pathologists, data specialists, and of course the engineers, which in the various optical and mechanical and electric field, all look at their own field, how to help us make a better TURB, make a better resection at the beginning and then get better ideas on how important, not important, but how aggressive a tumor can be and how much we have to do in the adjuvant or even in the salvage setting.

Alicia Morgans: Well, I think that you have certainly summed it up and what a masterclass it is. For you to do with the international bladder cancer group to really help us understand there is no simple to TURBT. We have to use the technology that we have now. And there is technology that will be on the horizon that will help us actually do the most effective to TURBT. But even this technique, which could seem like one that is your grandfather's TURBT continues to evolve and continues to impact patient outcomes, most importantly.

Arnulf Stenzl: Absolutely. I mean, it can be simple, small, popular tumor. It can be simple, but it can also be more complicated and it needs training. And there are simulators like the flight simulators, huh? There are simulators nowadays and in my department, before anybody is allowed to touch a patient with a resectoscope, he has to undergo a certain number on the simulator. And then he is so to say fit for an endoscopic procedure, which has consequences for the patient. So we have to think on the one hand, of course, it can be a not-so-complicated procedure, but we also have young aspiring urologists and they need to do their first one on the patient in a safe way so that he doesn't have any disadvantages. So training, then be prepared for the complicated cases or be prepared for the unexpected and then go on. And then, because it is an oncological problem, we need to work still on making it better, improve it for the patient's benefit.

Alicia Morgans: Well, that could be a motto for so many things in urologic oncology and clearly a motto for the optimal use of TURBT. I sincerely appreciate your time. And that you've shared your expertise with us today.

Arnulf Stenzl: Well, thanks a lot, Alicia. It was a pleasure to talk to you and then show maybe a little bit for the young and not-so-young urologist.

Alicia Morgans: Wonderful. Thank you.