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Phillip Koo: Hi, my name is Phillip Koo and welcome to UroToday. We're here at AUA 2023 in Chicago, and we're very fortunate to have with us Dr. David Crawford, Professor of Urology at University of California San Diego. Thank you for joining us, Dave.

David Crawford: Hey Phil, thanks for being here.

Phillip Koo: Tell us a little bit more about the RADAR articles. This is a journey that started, I think maybe 12, 13 years ago, something that you spearheaded from the beginning and has really had a huge impact, not just in urology, but in the prostate cancer community throughout the world.

David Crawford: Yeah. RADAR started, it was one of those things that started because of a need. And when it came to meetings like this and other meetings we do, we'd often hear somebody has localized prostate cancer, Gleason 6, PSA 5, and they were getting bone scans, CT scans and things like that, which we know was pretty much a waste of time. But there was a, "Well, we got to do it. It's a medically, legally necessary," and one thing after another. And we heard that and we heard that. So we got together a group in an advisory board to basically examine what the guidelines were out there, and they're all over the place and there was no consistency. And so that was really the genesis of and brought out by need to try and put this together.

And so we decided there were three areas that needed some work and one was biochemical failure, the other one was newly diagnosed disease, and the third was the castrate resistant nonmetastatic disease that we have now. And so what happened was we started out with, after looking at the literature and everything, that with newly diagnosed disease, that there were three things that probably you could consider as a reason to do scanning. And that's conventional imaging back then, which was bone scan, sometimes CT, and that was a Gleason score 7, a PSA greater than 10 or a nodule. So you had up two of those things and that caught on and we had data to support it. And when you think about it, the impact of that was significant just in a cost savings to the healthcare system about doing that.

And then the other area is biochemical failure and depending on who you believe, they're anywhere from 40 to 60,000 men a year that fall into that category of rising PSA after failed local therapy. And again, somebody's PSA was 0.5 and they get a CT scan, they'd get a bone scan, and it turned out to be pretty much a waste of time. And we didn't have much to offer. We said, "Okay, maybe it should be a greater than 5, and then when it doubles, do it again, do the scans." But you don't keep doing scans on somebody with a PSA of 1 or something like that.

And then the whole thing with non-metastatic castrate resistant disease, again, it was the same thing. What are your triggers to repeat your scans? And so that was sort of the genesis of it and it turned out to be very successful. And as a matter of fact, for about five years, it was the most downloaded article in advanced prostate cancer and prostate cancer. And we published the article actually nine years ago now. We started working on it a couple years before.

And then the RADAR, it sort of grew and it grew into let's look at the data and let's figure out how to implement it. And so what happened was RADAR II was about all the drugs out there, the new drugs, and we came up with this term called therapeutic layering where we continue ADT and you build on that. But the big change came with RADAR III again, and that's when we started getting some of the PET imaging and things out that we have and fluciclovine. And then there were some earlier studies that were out there for imaging, as you well know, you were involved with them. So what we said is, "Hey, we got to redress this and look at this again." So for the newly diagnosed disease, we said, "Hey, look it, you have guys come in to see you. Their PSA's 30, they have a Gleason 9 and their conventional imaging is negative. What do you do?" And that's what, "Hey, maybe these new scans will help the fluciclovine Axumin and things like that." So that was a big set.

And then in the area of biochemical failure, we were beginning to feel like you could probably scan people with a PSA of less than 1 and maybe find something. And then we did a little bit with advanced disease. And so that was the RADAR III. And then you were one of the people that came up with this terminology, NGI, next generation imaging. And that was a turning point. So RADAR continued to sort of sit there, but then the RADAR IV and V were just implementation things. But what we did was took some deeper dives looking at the data saying, "Hey, what we really want to do here is we don't want people to get to a castrate resistant state and we should throw everything we can, therapeutic, layering, whatever imaging to try to keep people from making that transition." Because when that occurs then people are sort of on a limited lifespan. And I have people with metastatic disease of life 15 years that I've treated and many of us do. But when you get to that point, we have some things to offer and it's getting better.

So those were the things that we came up with the whole new that we have these disease state diagrams where people start out with rising PSA, surgery, radiation, fail, metastatic disease. So we came up with us the concept of, "Hey, let's try to not have people transition into that thing. So let's do our best to do it." And then, as you know, we had some major advances with PSMA and other forms of PET imaging and you've been on the forefront of that and that led to RADAR VI and VII.

Phillip Koo: So before we get into VI and VII, just to summarize, I think looking back at RADAR, first off, congratulations. I think your vision and being able to see the future and really find ways to impact how people practice today, I think has been so important in how we manage our patients. I love the fact that with imaging, you really focused on appropriate use. How do we utilize these tools appropriately and also not overutilize them? And that was with conventional imaging because you saw a need where it was being overutilized in patients with low risk disease and underutilized in patients with advanced disease, which isn't good as well. And then we talked about implementation. I think that term therapeutic layering really was so important and really had a lot of implications I think, in how we thought about how we treated patients.

And then we sort of moved forward. And that concept of delaying castration resistance, I think is really important and profound and I think that was an important topic to dive into. And I love the fact that it was multidisciplinary. You really brought a group of experts of all different specialties to really discuss this and come up with the best answers we could given the data that was available. So you sort of gave a teaser into this RADAR VI and VII. And you're right, I think PSMA has clearly changed what we do today. And you recently published these, were the first author and two of these RADAR VI and VII that were just published in the Journal of Urology Open Plus, which we just interviewed [inaudible 00:08:03].

David Crawford: Right. We were one of the first articles.

Phillip Koo: Yeah. And is actually the most downloaded article.

David Crawford: I know, I just saw that.

Phillip Koo: Yeah, so congratulations on that. Can you just give us an overview of those two articles?

David Crawford: Well, yeah. One of the things you brought up is, are they called guidelines, pathways? That rings different bells with different people and say, "Well, who has that?" Guidelines are not mandates and there are guideline committees and different ways to do things. NCCN has them, AUA has some things like that. There's also the level one evidence, large trials and one thing after another. And we don't really call them guidelines or sort of pathways, we got a group of people together that know what's going on. And I think that carries a lot of weight. Sometimes you get criticism for that, well, you got a smoke filled room with a bunch of people. That's not the way it worked. These people worked hard. We looked at things, we talked about it, we crafted it and we tried to implement it.

And I think that the thing that really has sort of happened was we now have more tools. And there've been some real significant things happened the last 10 years in prostate cancer, last five years, last couple years. And the PMSA based scanning is clearly one of those. And then that's hooked up as you well know that there are theranostics. So there's another game changer. And that's when we, and again, credit to you, we had next generation imaging and said, "Hey, it's not next generation anymore, it's here." And so we came up with the whole idea, MTI, molecular targeted imaging is a new name for it. And I think that that's starting to catch on. And what is it?

Well, basically now we've got some really some fun things going on and some challenges. And there are really good studies that have been done with newly diagnosed disease and showing the value when we all see these people that have PSAs of 40 Gleason 9s and nothing there. Now we're doing scans and we find things, but I think the one thing that you said and everybody said is when you order these things, it should be actionable. You're just not ordering them to be ordering them. You're ordering them because it's going to make a difference.

And I think we're going to learn where it helps and where it doesn't. But clearly one of the big things is newly diagnosed disease and seeing lesions in the prostate, lymph nodes, all this other kind of stuff. We see it all the time. And the other biochemical failure is a game changer in a way. But of finding this and then being able to spot, radiate, remove whatever you're going to do, nodes and it changes, it sort of changes the direction around.
And then the big thing, and I'm not going to take deep dives into RADAR VI and VII, there are tables that are there, but basically they say, "Hey, we got to step cautiously." We just can't say, "Hey, this is the way it is." But we want more data. But we at the same time want to continue to move forward. Not to say we're going to put up a roadblock and we're not going to do imaging unless X, Y, or Z, but we're sort of pointing to the fact that, you need to document stuff with biopsies, a lot of this stuff to prove it. And again, you've been on the forefront of talking about false positives and [inaudible 00:11:46] and things like that and not making a mistake and knowing how to read these. I've seen people that have been say, "Oh, they got a lymph node there or something" and it turns out to be a ureter, things like that. So there's a lot of learning that needs to happen, but that's no reason to not move forward with this.

And so, as you know, one of the big things is we've got all these that we created this iatrogenic disease called non-metastatic castrate resistant prostate cancer from giving hormone therapy to men that have biochemical failure. And now we did all this scans and they were negative. We got drugs approved in that arena, and now we start doing the PSMA and fluciclovine scans and other undefined metastatic disease, what does that mean? And so is that going to change that around? Yeah, that again, those are the things that are discussed in the RADAR VII, which is sort of the implementation of the findings of VI.

Phillip Koo: That's wonderful. For those listeners out there, be sure to go to the Journal of Urology Open Access Plus website, download those two articles. I think a lot of great information there. And again, I agree there's a lot of questions that it brings up and obviously a lot of opportunities and areas that we need to address moving forward. So thank you very much, Dr. Crawford for your time, and we look forward to hearing from you soon.

David Crawford: Thank you, Phil.