Matthew R. Cooperberg: Hi. I'm Matt Cooperberg. It's a pleasure to welcome you to another installment of the Clinically Localized Prostate Cancer Center of Excellence Interview Series for UroToday, finally, one in-person. I am thrilled to be joined today by Dr. Sanoj Punnen, who is Associate Professor at the University of Miami, and a newly minted Vice-Chair for Search at that institution. We're going to talk a little bit today about the rapidly evolving prediagnostic space for men with elevated PSA and trying to figure out what to do with the biopsy decision. Dr. Sanoj, welcome. Great to have you here.

Sanoj Punnen: Thank you, Matt.

Matthew R. Cooperberg: Tell us a little bit about this evolving space for men who have elevated PSA, who are trying to make a decision whether or not to do a biopsy. What do you think of as some of the highlights in terms of research progress and the growing armamentarium in this space?

Sanoj Punnen: Well, I mean, as we all know, PSA is good for a screening tool, but it doesn't really help us differentiate those guys that have bad cancers versus something that doesn't need to be treated. I think that's kind of led to a open space for lots of liquid biopsy markers to come in and fill a niche that we didn't have. We also see imaging in that same area as well, MRI. I think one of the areas of excitement for me is really looking at trials of how we can use those together. I think we've seen a lot of opportunity where paralleling an MRI and a biomarker together is improving either one alone, but how you sequence them and what your practice is like and which is better for you to go with, I think, is a real unanswered question right now.

Matthew R. Cooperberg: How are you answering that question? In terms of PSA, marker, MRI-

Sanoj Punnen: Biopsy.

Matthew R. Cooperberg: ... biopsy... Sorry. PSA, MRI, then marker, you do both in parallel?

Sanoj Punnen: That's a good question. I think when I first started, I was doing both together just to get more experience with them, trying a variety of different markers as well. I think my approach has been now going with the MRI first. The only reason I do that is because I think it's specific to my practice. I have a lot of patients that come in with MRIs. We have easy access to good MRIs and good radiologists, more importantly, that you can trust. At least for me, knowing that the MRI provides you some imaging information about where to target, if that shows something, you're going to probably do it. I also feel very comfortable reading my own MRIs, which I think is an important thing as a urologist. For me, that's kind of where I start. Then after that, if the MRI is either high RADs three equivocal or negative, that's where I'll go to a biomarker. I like that approach partly because for a person not to get a biopsy, they technically have to be negative on two different studies, so you're extra sure.

Matthew R. Cooperberg: Negative MRI, positive marker, you'll do a systematic biopsy.

Sanoj Punnen: I tend to. Yeah.

Matthew R. Cooperberg: Do you have a biomarker of choice?

Sanoj Punnen: I tend to go with two. I have a blood marker and a urine marker. I use both the 4KScore and exosome. During COVID, actually exosome. I rolled out a at-home collection kit and we were doing so much telehealth as I'm sure you guys were. That was a great tool to have.

Matthew R. Cooperberg: Yeah. That timing was really incredible. We did a ton of it for exactly the same reason. I think it's a great test. I don't know if it's any better than the others, but the fact that they had that home kit, the timing could not have been better.

Sanoj Punnen: Yeah. They had that availability, the patients really liked it. I remember when they were talking about it, I wasn't so sure it was going to have the impact that they thought it would. I was wrong. It's been great.

Matthew R. Cooperberg: Yeah. Well, the COVID-19 pandemic. I don't know if you've got an experience with the polygenic risk scores in this space. It's very interesting because I think some of the research teams that are promoting them, are promoting them even in a pre-PSA question, which has always struck me as a bit of a stretch from the standpoint of a primary care doctor and making decisions about this. Do you see them there versus competing against 4K, selecting exo, and all of that?

Sanoj Punnen: Yeah. I think it could speak to the same thing. I mean, it's a little bit different in terms of the polygenic risk score and what they're actually looking at. From what I understand, it's not exactly one collection of markers or genes that you're looking for. In that sense, I think it's still a little hard to see how it's going to fit in, I think there's some utility to it. We're actually talking more and more to them. We have an active surveillance trial that we've finished accruing and I want to look back. We have plasma on that. They're thinking about looking bad as well. I think there could be a role. I just haven't had enough experience with it.

Matthew R. Cooperberg: Yeah. All right. You've also been involved with work on using AI to improve MRI. It's great to work in the center with good radiologists, but not everyone does. Even those of us that do, there's still obviously space for improvement. What's going on at your place and elsewhere?

Sanoj Punnen: Yeah. I've always been a believer in quantitative imaging. I think there's going to be a lot more in terms of the numbers of how dark something is relative to how you look at it subjectively. I do think there's a role for this in terms of standardizing how we look at things. We're actually doing a trial. As you know, we created a in-house software. It was made by a nuclear physicist at our group. This identifies the prostate segments in a peripheral and a transitional zone and applies what we call habitat risk scores to different regions. We've been looking at it retrospectively in our prostatectomy specimens, and it seems to do a great job finding a lot of the great group too, that our MRI had missed. We're evaluating it right now perspectively in a trial for the elevated PSA population. We got a collection of markers in that, too. 4K, exosome, the MRI with its AI components. It'll be nice to see how all of it comes back together.

Matthew R. Cooperberg: That's great. Is it just a single institution?

Sanoj Punnen: It's a single institution, NCI-funded though.

Matthew R. Cooperberg: Yeah. Is the MRI technology exportable? Is this a plug-and-play package?

Sanoj Punnen: Well, so far, it's been something that we do at our institution. We do know that at our institution alone, we have five different MRI vendors. That's always been a problem with AI. When you get a different vendor, it doesn't work. We've had the luxury of being able to train this on many different machines, and we're taking outside MRIs as well. It's not just our in-house MRI that we're looking at on the trial. I would imagine in that sense, it will be more generalizable compared to your single institution, things that were brought up in one type of MRI.

Matthew R. Cooperberg: Any sense about any of the commercial MR projects that are starting at the market?

Sanoj Punnen: Yeah. I mean, look. We'd like to take it that way. For us, I think we want to continue validating and show more research because I feel like there's a lot of things that have gone in that direction and we're not sure. That whole issue of just multiple vendors and things like that with MRI, make that a little bit more difficult, I think, let's say a biomarker.

Matthew R. Cooperberg: Yeah, yeah, yeah. Where do you think the future is in this space? Both in terms of the imaging, I mean obviously, AI has got a huge role to play. What do you think the next steps are in the liquid space?

Sanoj Punnen: I really think the next steps will be combining liquid and markers... Imaging, sorry. Whether I think, PSMA is an exciting tool as well, and how that's going to come into this space and work with an MRI. Ultimately, I do feel as good as liquid biopsies are going to be. Imaging is going to be a key part because it does give you the information of where you're going to direct that biopsy. At least in my mind, I feel like that will play the forefront of how we're going to start evaluating patients, but it's never going to be perfect. There's always going to be a role for some sort of liquid biopsy, but where I'm most excited about that is the follow-up potential on those. I actually think an active surveillance, for example, we know that MRI, just standard-of-care MRI, doesn't do a good job monitoring things. We've really looked at liquid biopsy in the elevated PSA space, but I don't think we've given it a fair shot in the active surveillance space, especially in monitoring. I think that's where certain biomarkers, for example, like exosome, the technology they have, and being able to get the exosome, extract the RNA from it. You can find a way to get exosome specifically from prostate cells. I think that would be very exciting for surveillance.

Matthew R. Cooperberg: Last question. Any sense about where micro-ultrasound exact view is going to play? Any experience with it?

Sanoj Punnen: Yeah. Great question. We just got it, actually. I did trial it and I really liked it. The imaging definition gets phenomenal. I think it's going to have its issues like anything else. There's a lot of user variability with it and you got to get used to it. I look at my own MRIs and we get used to looking at imaging. This is going to put a very powerful tool right in the hands of the urologist. I'm excited about that. The other thing actually we do, you do, and I do, a lot of MRI ultrasound fusion, we both know that there could be a lot of error just by the misregistration. To me, doing an MRI, and then a cognitive micro-ultrasound biopsy, that I think is going to be the way to go.

Matthew R. Cooperberg: So you don't see this is necessarily replacing the MRI anytime soon?

Sanoj Punnen: No, I don't, because I still think most of my patients would prefer to have a 40-minute MRI in the coffin as opposed to a trust. In that sense, I think the MRI will still be the start.

Matthew R. Cooperberg: Yeah. Excellent. Any other thoughts?

Sanoj Punnen: I think you covered it all. I think bringing all these things, that's an area where I think is going to be super exciting is AI in the micro-ultrasound. That I think, will be hopefully, where we'll start to see things go.

Matthew R. Cooperberg: Maybe it'll actually get augmented reality. We can get it. It seems like it's heading that direction.

Sanoj Punnen: It's possible. Yeah, absolutely. Using it for focal therapy, I mean, this is the thing. It's an exciting time in urology right now. I feel like we have a lot of micro-ultrasound, PSMA. MRI is still growing, and now all these liquid biopsies. I think we're lucky to have all these tools. The next step is finding out how to use them the best possible way.

Matthew R. Cooperberg: Could not agree more. Thanks for joining us. Good to see you.

Sanoj Punnen: Oh, awesome. Great to be here.

Matthew R. Cooperberg: Thanks your time.

Sanoj Punnen: Thank you.