Ashish Kamat: Hello and welcome to UroToday's Bladder Cancer Center of Excellence. I'm Ashish Kamat, Professor of Urologic Oncology and Cancer Research at MD Anderson Cancer Center. And we have today with us Dr. Max Kates, who's Associate Professor of Urology and Oncology and the director of a Bladder Cancer Program at Johns Hopkins Medical Institution. And joining us a little bit later is going to be Professor Trinity Bivalacqua, who is director of Urologic Oncology at Penn Medicine.

We're going to talk today briefly about blue light cystoscopy in general, but specifically about the new system that was just launched, a SAPHIRA system, and discuss its implications with Cysview. So Max, stage is yours.

Max Kates: Thank you, Ashish, for having me. I'll briefly just review blue blood cystoscopy with Cysview, and then I'll show you some very exciting images from the new SAPHIRA system and we'll talk about implications of that.

Just to review, why is enhanced cystoscopy so important in bladder cancer? And that's because bladder cancer is a life-long disease. It has an extremely high burden to our healthcare system and there is a need for surveillance through many, many years of a patient's life, and a need for surveillance through many, many years. And after a patient is diagnosed, from that time point forward, having enhanced techniques to detect recurrence and impact management is essential.

Cysview is instilled as a photosynthesizing agent that interacts with the heme biosynthetic pathway, and it selectively selects for intracellular accumulation of photoactive porphyrins. And these porphyrins preferentially accumulate in rapidly proliferating cancer cells. And so after one hour of installation of Cysview, that is sufficient to essentially have blue light illumination of neoplastic cells fluoresce bright pink.

And for that, based on a lot of data that we won't discuss in this session, blue light cystoscopy and enhanced cystoscopy in general is now in both our AUA and NCCN guidelines, within a moderate recommendation with an evidence grade of B. And many of us use blue light cystoscopy at various points in a patient's bladder cancer journey, particularly during TURBTs and particularly during things like restaging TURBTs in the setting of surveillance as well. And in situations in which there is a cytology of unknown origin, or an abnormal cytology where we don't know quite the reason for it.

Now the standard blue light cystoscopy system that was used for many, many years was this rigid system on the right that had a separate camera head and scope set and light cord. And this is the tower many of us are familiar with. And more recently, those of us who use flexible blue light system, may have the flexible system. When we look at those scenarios in which blue light has historically been most helpful, it's in these subtle satellite areas.

So in the top left corner, this is a patient perhaps with a high-grade, non-invasive papillary lesion who may have a small foci of cancer cells in a satellite lesion right above, that some of us may have missed. Or in the lower left corner situation of a cytology of unknown origin where many of us may not have been able to see a small lesion such as this in the bottom left corner. And that's reflected in both of the images on the right. These are the scenarios in which many of us find blue light quite helpful to detect both satellite lesions and these subtle areas of perhaps CIS or a very small high-grade TA lesion, that over the course of a patient's cancer journey really impact outcomes.

But this new system by SAPHIRA is quite exciting. And basically I like to think of it as, for me, the first time using it was going from the standard television sets from the early '90s to high definition sets, and that's really what it looks like in practice. And essentially it's a power LED light source with a different camera head and light cable and a completely new tower set. And what it is able to do, it's able to have this system called CHROMA, which I'll go over in the next slide, actually it's a slide after this. But this is basically the way it looks in the new tower with enhanced optics and imaging.

And so this is the case I wanted to go over with the new system. This is a 65 year old gentleman referred with newly diagnosed high-grade T1 with CIS, was brought to the OR for a restaging TURBT with Cysview using the new system. This is the standard view. And then when it goes to CHROMA you see immediately all of these vessels, all of these blood vessels, immediately are very apparent. And what that allows you to see is that actually there's this patch of erythema that's very clear on the right side of the screen.

And then, when we put on top of that blue light, immediately we confirm that this area is in fact a blue light avid area. So the combination of the CHROMA with this blue light really confirms what would be considered our boundaries of what we think is probably a CIS lesion. And in this scenario the reason ... And with the new system you can modify the intensity of the blue light to confirm the borders and the edges of the light refraction. And what that allows for is the overarching goal of, is this a lesion that we can resect confidently. And one can see that clearly, in my hands using this, the answer is yes. And so this is really exciting so I wanted to show this video.

And so we resected this lesion as if it were a standard papillary lesion or historically something that we thought was a fully resectable lesion. And in this case it was a patch of CIS, but because of the combination of the SAPHIRA and the blue light, we were able to see the markers fully demarcated. And so on this restaging TURBT, the final pathology was CIS and the plans for induction BCG.

I highlight this case to show perhaps how in the long-term we may be able to impact patient outcomes through this technology, although that needs to be determined.

Ashish Kamat: Great. Thanks so much, Max. Those are some really good images. A couple questions so we can highlight a few points. With the new CHROMA system with the blue light, that is the existing CHROMO system that Storz has, correct? And it adds upon the ability of the tower to interface with the blue light technology essentially.

Have you had much experience using the CHROMA system without blue light? And if so, for those in the audience that might be thinking, "Well, should I just do CHROMA and leave aside the blue light," could you share some of your insight there?

Max Kates: Yeah. I mean, so I have had experience using the CHROMA without the blue light. And my answer to that would basically be, I think all improvements in medicine, but particularly in bladder cancer, are iterative.

So basically, if CHROMA is more helpful than standard view, which I believe it is, and if I see a patch that I believe is CIS through CHROMA, then if I use blue light and I confirm the edges, then basically each one of those tools is enhancing ultimately my resection. And so that's how I would answer this, I believe both are helpful and additive.

Ashish Kamat: Yeah, and I agree with you because I've had a lot of experience with CHROMA by itself. Yes, it certainly makes things easier to see, and like you said, it's almost like going from SD to HD to 4K and even 8K. I mean, you can actually see lesions pretty well. But the biology of the lesion is only brought out when you actually combine it with the blue light because that's where you're using the enzymatic conversion, et cetera, et cetera. And I agree with you, we need both.

Again, like you said, it's an incremental benefit, but it is a benefit and it's heading in the right direction. Would you encourage those that are listening in that have maybe the existing system with the blue light, with the standard storage system, to look into the CHROMA system? Or, in your opinion, is it important to first get the blue light itself, depending on budget constraints, and then look at the CHROMA system?

Max Kates: Yeah, that's a great question. I mean, I think find both to be helpful. I think that you have to look at what resources you have available at your institution. But I think having the blue light is I think most helpful for delineating, to your point, the biology of what you're looking at.

So I think it's probably most helpful, but of course we're always looking to improve the actual optical, what we're exactly, as you said, looking at, 4K, 8K. So probably first I would want to have a blue light system and then next I would want to bring on CHROMA. But I would love to not have to make that decision.

Ashish Kamat: I know, absolutely. And one of the things that we always talk about is that the way to get better penetrance of blue light in the community or elsewhere is if it were not dependent on the technology from a particular company, as far as the actual scope and camera's concerned. But be that as it may, in the US it is approved in conjunction with Storz and we can't get away with that.

With that in mind, it is really important for folks that are listening in to recognize that there's a difference between the technology, which is Storz CHROMA system and the blue light, which is the agent that's instilled in the bladder. But like you showed in your pictures they work well together, so it's not like we're asking people to choose between one and the other. They're both complimentary essentially technologies in some ways. One looking at the biology and the other one just improving our resection.

Some pearls for our listeners, because obviously we have some early career folks listening in and even some trainees. When you're resecting these tumors, do you still tend to switch to the non blue light for your resection? And if so, have you found the CHROMA system to really help with the margins like you suggested? Or are you experienced enough and would you recommend people, once they have good experience with blue light, that they could stay in the blue light wavelength, even during resection?

Max Kates: Yeah. I'm constantly training residents and fellows in doing and using these techniques, and my preference is to go in and out of blue light. Sometimes that'll mean resecting even under white light. Sometimes that'll mean, depending if I'm comfortable, which I am usually, resecting under blue light.

But I also do like to go in and out of white light and blue light. I find, once again, that it's only additive and just confirmatory. So I do tend to go in and out. Yeah, I'm wondering what your experiencing is with that?

Ashish Kamat: Things have changed so much. Back in the day, I remember in the late '90s, '99 or so, when I was using blue light for a resection, there was a distinct lag between what you could see and what you were doing. It was measured in the milliseconds, but it was distinct enough that it was a little bit scary if someone didn't have a lot of experience, because before you say "oops" you might have a perforation. And the dogma was, do not resect under blue light, do not resect under blue light.

And that lasted for at least a decade. I think it was summer on 2010 when the camera system improved a whole bunch that you could actually have still a little bit of a lag, but not so much. And now when I train the fellows and residents I actually want to resect under blue light all the time. But I think for some reason the literature and even the textbooks sometimes state you shouldn't resect under the blue light. I think that's the old teaching, but I remember those days. That was actually scary, because you're like, "Stop," and before you could actually finish your OP the next step had already occurred. And of course if you're doing, it's one thing, but when we're training people, which we need to, to improve the care of patients everywhere, that was a little bit scary.

Max, as always, it's great chatting to you about all things bladder cancer and our audience learns a lot from you. Any closing thoughts you want to leave our listeners with as far as this new system, how you perceive it, what you're looking forward to in the future from the whole blue light technology?

Max Kates: Yeah. I mean, I just think this is one more step in what we're all looking to achieve, which is to make TURBT the golden technique that will dictate outcomes for our cancer patients in the most positive ways. So the more even small steps we can do to improve TURBT and enhance our TURBT techniques, is going to have dramatic impacts on our patients' experience and outcomes moving forward.

So that's kind of how I view this, and I think there'll be many iterations of improvements to come.

Ashish Kamat:  Absolutely, well said.

Ashish Kamat: Dr. Bivalacqua, what are your thoughts on how this new technology, especially with the images that Max showed, improves upon the current technology that we have in the blue light system?

Trinity Bivalacqua: Yeah. I think in my experience, utilizing the new visualization system with SAPHIRA, it really does help us identify tumors readily. It is much sharper, and I think my ultimately feeling using it currently is that kind of helps us teach our trainees and teach the fellows the ability to use blue light in clinical practice because it's a much better image. I'm hopeful that in the future it allows us to have less false positives and be able to detect maybe CIS lesions and papillary tumors more readily.

It's clearly an improvement in the visualization system, but ultimately it's blue light cystoscopy. So my experience is that the more you do, the more you figure out how it fits into your clinical practice and allows you to improve upon detection of tumors, and hopefully that translates into a reduction in recurrence.

Ashish Kamat: Yeah, that's a great point. But leading into that, because sometimes we'll hear people say, "Do I need the new CLARA CHROMA system, or can I stick with the older generation optics that I have and still use blue light?" To those folks that are looking to maybe look at the incremental cost-benefit ratio, what would you say? Should they necessarily invest in the new system or is it more important that they learn the blue light nuances first?

Trinity Bivalacqua: Yeah. My opinion is is that it's blue light technology is really what matters, and your ability to use it in your clinical practice and get experience using blue light is I think ultimately what is going to improve upon your outcomes in patients with non-muscle invasive bladder cancer.

I can tell you, in my experience, we were ready for an upgrade, so this was perfect for us because we were able to upgrade to the new technology and bring this into clinical practice and use it for teaching and as well as obviously for patient care. I think actually learning blue light and learning how to use it in the operating room and how to use it to resect tumors, to detect tumors, to biopsy and whatnot, is probably really what matters for most urologists that are taking care of bladder cancer patients.

Ashish Kamat: My take on the new system is that, even in instances when we don't actually use the Cysview agent, just having the better visualization, the ability to increase the contrast and look at the overlay, does help, not only me sometimes, but it definitely helps when we're training our fellows and residents. Has that been your experience as well?

Trinity Bivalacqua: Yeah. That's exactly what my experience has been. And it's interesting, residents and fellows really look towards new technology and they embrace new technology. And in my experience using the new system, really people are excited about it and really are interested in learning how to use it. It's almost like it reinvigorates the team.

It's interesting that the nursing staff and the operating room also are interested in it and the whole team is just excited about using it. And I do think that it definitely improves upon visualization, at least in my experience.

Ashish Kamat: In closing, again, Max gave us his closing thoughts. Some closing thoughts from you as to the take-home message for our audience?

Trinity Bivalacqua: Yeah. I think my message to anyone listening is, is that blue light cystoscopy does help improve detection of more tumors, and with the new SAPHIRA system you have better visualization that improves upon, at least we're hopeful that it improves upon detection, and ultimately reduces recurrence. I think the technology is excellent, and I think this is a small improvement in the ability for us to manage patients with a non-muscle invasive bladder cancer to the best of our ability.

Ashish Kamat: Absolutely, well said. Once again, thanks for taking the time and hope to see you in person soon.