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Zachary Klaassen: Hi. My name is Zach Klaassen, urologic oncologist at the Georgia Cancer Center in Augusta, Georgia. I'm pleased to be joined on here today by Dr. Matt Cooperberg, urologic oncologist at UCSF and the San Francisco VA. Matt, thanks so much for joining us.

Matthew Cooperberg: It's a pleasure. Good to see you.

Zachary Klaassen: So we're going to talk today. You guys have recently launched a new endeavor looking at OnQ Prostate‑assisted Focal One Robotic HIFU. Just by way of background, just to set the stage for who’s a candidate for focal therapy, just go through your criteria, especially for focal HIFU—who might be the right candidate?

Matthew Cooperberg: Yeah. Look, that in and of itself, I think we could talk for about an hour.

Zachary Klaassen: Right.

Matthew Cooperberg: Yeah. I would say, first of all, it’s in very rapid evolution. When I was a resident, which is getting to be a few years ago, HIFU was a four‑letter word around UCSF because the outcomes were terrible, and we didn’t really know who the right candidates were. I think we are learning. There’s been a lot of progress in the literature in recent years, but it’s still very much in evolution.

And I think the principles—we actually had a consensus statement out for the five University of California sites just a couple of years ago—really emphasizing a few major points. Number one, that we really should be using focal therapy for patients that need treatment. We should not be treating grade group 1. It’s over‑treatment with HIFU no less than it is with surgery or radiation in the vast majority of those cases.

There’s a sweet spot of patients who need treatment, but don’t need whole gland and regional pelvic management. And the challenge is finding those. So the ideal candidate has an imaging‑visible lesion, so visible on ultrasound and/or MRI, and no more than a few specks of 3-3 elsewhere in the prostate that we know we are not going to treat.

So in the ideal case, we’ve got a visible lesion with a grade group 2, or maybe even a grade group 3 and favorable genomics, and maybe two cores of 3-3 on the other side that we’re not going to worry about. But that statement—“we’re not going to worry about it”—really emphasizes the point that whether or not we are leaving grade group 1 behind, these patients are still on surveillance.

And the framing in the conversation around who’s a candidate has a lot to do with how we’re presenting it. And I think that’s actually evolved quite a bit. It’s really driving the conversations we’re having about what the next trials need to be. And we’re having some great conversations about what the next trials need to be. And I think the evolution is really that focal therapy is not an alternative to surgery or radiation. It is an adjunct to active surveillance.

And we’re really thinking about focal... The way I’m presenting focal these days is for patients who are either really borderline candidates for surveillance, or frankly not great candidates for surveillance, but are still really looking to avoid whole gland therapy. This is the sweet spot. And we fully recognize in many of these cases, we’re just kicking the can down the road some number of years.

The recurrence rates at all the major centers that are doing a lot of this are high, well into double digits—30%, 50%. But as long as we’re not missing a window of opportunity for cure, and as long as we can still come in with surgery or radiation therapy down the road without compromising the outcomes of those procedures, then we think we’re relatively safe.

Now, there are—we’ve all seen small numbers of cases which come back much worse than before. We’re starting to get together to try to figure out how to characterize those cases better. And so it’s evolving very quickly, as I said, and I think identifying who is the right candidate is one of the most important questions in the field.

Zachary Klaassen: Yeah, I’m glad you—that’s well stated. And I think your point of “get these patients back to active surveillance candidacy,” I think that’s a great take‑home message, even just starting out this conversation. Let’s pivot to OnQ Prostate. So how does this technology help with identifying these patients easier?

Matthew Cooperberg: Yeah. So I mean, I already alluded to this, but the whole challenge with focal therapy is not so much delivering energy; it’s figuring out what part of the prostate needs that energy. And we’ve got a half a dozen different modalities, at least. And there’s lots of different ways to destroy a little piece of the prostate. The question is-- and there's and those energy sources are much better controlled than the earlier generations. The question is, —do we know what we’re treating?

Traditional imaging, both ultrasound and MRI, are certainly imperfect. There’s a lot of issues with interobserver variability around MRI. And so we’re very interested in the technologies that are coming down the pipe to improve what we’re able to do with ultrasound and MRI. And actually, PET CT may have a role in this area as well. And one of the critical things is making sure we’re not undersampling the cancer.

So there’s a few different technologies we’ve been working with. UCSF radiology has led the charge on MR spectroscopy for many years. This is still, unfortunately, an expensive and pretty niche technology. You need a polarizer. You need a whole separate apparatus to be able to do this. So it really has never taken off even at our institution. And there’s a number of AI strategies which are coming down the pipe to do better with the existing sequences that we have to help do better targeted biopsies.

And then OnQ, which we’ve just started working with recently, is an implementation of something called restricted spectrum imaging. And I’m going to say this as the dumb urologist who knows just the bare minimum about the MR physics. This is basically fancy DWI. So diffusion‑weighted imaging is really looking at restricted flow of water and, therefore, proteins through cancer, which has a higher density of cells, higher cell membrane to water ratio, relative to the surrounding prostate. So you see less flow of protons.

Restricted spectrum imaging is basically, to my understanding, leveraging that same phenomenon, but does much better math on it and is giving us a better signal‑to‑noise ratio. And then the actual implementation through OnQ has the nice advantage, again, for us clinicians of actually creating these nice color maps. So in terms of targeting, we’re studying this both for fusion biopsy and in this pre‑HIFU, HIFU planning framework.

And one of the nice things about the Focal One platform, in particular, that we’ve been working with at UCSF for the last couple of years, is we can do real‑time MR‑guided planning and actually draw our circles for our targets based on this enhanced additional sequence.

Zachary Klaassen: Absolutely. And I think you have a couple of pictures to show us, just to highlight some of those points that you made.

Matthew Cooperberg: Yeah, let me flash up. And the one I’m going to show is not actually our first type of case. It’s a different one, but it will illustrate the point. So this is the RSI sequence here. And, again, we get these probability heat maps.

And what you can see in this case—this is overlaid on the T2 sequence here. And obviously, there is some overall correlation, but we do get a much better sense here of the RSI signal really kind of approaching the capsule of the prostate, more so than the T2 alone indicated. And I will say this was a patient who actually had EC on biopsy. So this is a good example of a true positive here.

In some of the cases—and I will fully admit, our experience with this is relatively early. Michael, this is one of the other folks who’s been doing a lot of this and really getting them on the map. But there are definitely cases where the T2 and the traditional DWI are a lot less clear and more ambiguous.

The pre‑HIFU case that we did actually had bilateral lesions. One of them was much closer to the urethra. So having this additional information, I think, again, especially this—it’s a very visual treatment in a way, and it’s a very image‑guided treatment. So the ability to get more precise with where we are drawing our margins for ablation based on this sequence, I think, is going to be very helpful. This is early days. We are looking to build this into some prospective studies ongoing, both for HIFU planning and, critically, for post‑HIFU assessment.

So as we said, we still need active surveillance after focal therapy. Without question, you need the one‑year biopsy. And this is an area where there’s probably even a greater need for better imaging than there is in the upfront, pre‑focal setting. We know explicitly that MRI does not work very well in the post‑ablation phase of things.

Obviously, we would like an imaging test that says, we don’t have to do the one‑year biopsy. But we clearly do not have one yet. So everybody’s getting a biopsy. And we’re looking very actively at RSI, at PET, and other sequences—other modalities—to try to come up with better ways to follow these patients without having to do multiple biopsies as time goes on.

Zachary Klaassen: Yeah, it’s great. I think you guys have just recently launched this program, OnQ with Focal One Robotic HIFU. Maybe just talk briefly about that. And as you mentioned and alluded to already a little bit, what is going to move forward over, let’s say, the next year or two with this platform?

Matthew Cooperberg: Yeah. It’s been collecting a lot more data. So we want to start doing this much more routinely with the, like I said, with the post‑HIFU biopsies. Katsuto Shinohara and Hao Nguyen at UCSF are doing the lion’s share of these. We have an experience now of almost 300 cases over the last several years. And a lot of those patients are starting to hit their one‑year mark. So doing this more pervasively and more prospectively to actually figure out what the positive predictive value, negative predictive value look like is going to be very helpful.

And then it’s harder to quantify the benefit at the time of ablation itself. But we are looking to bake this into ongoing planning for some very interesting trial ideas that are being talked around this West Coast collaborative, which has coalesced. I think a dozen institutions now all really interested in collecting much better evidence and running trials around focal therapy.

Zachary Klaassen: Awesome. Great discussion as always, Matt. Anything we didn’t touch on, any take‑home messages for our listeners?

Matthew Cooperberg: No, I think the take‑home—this is an exciting technology. I think it’s going to help in an area that’s got a lot of excitement around it, but really needs better data and better imaging, specifically. So this has been a terrific collaboration with both of the partners, so far with OnQ and with Focal One, both being very supportive of our efforts around focal therapy.

I think it’s our job in urologic oncology to make sure we’re doing the right trials and collecting the right data to validate these technologies, and to make sure that we’re presenting it to patients in a way that’s honest in terms of the state of our data—which I think, more and more, it seems like we are as a community. So I’m optimistic about the future in this space.

Zachary Klaassen: Yeah, well said. And congratulations on the initial work. And we’ll follow‑up with some data hopefully soon.

Matthew Cooperberg: Thanks, too.