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Dr Alicia Morgans: Hi, and welcome to ASCO 2018. I am very excited to have with me here today, Dr. Phil Koo, who is the Division Chief of Diagnostic Imaging at the Banner MD Anderson Cancer Center in Phoenix, Arizona. Thanks so much for being here with us today.

Dr Phil Koo: Great, thank you for having me. I'm very excited to be here.

Dr Alicia Morgans: Great. So, just especially thrilled to have someone speak to us about the new RADAR III. The guidelines that are coming out, the recommendations that are coming out, consensus panel, can you share a little information about those? 

Dr Phil Koo: Sure. RADAR first started in 2012. It was chaired by Dave Crawford. In 2012, I think he and many others saw a need for recommendations with regards to imaging and detecting metastatic disease. There really wasn't clear guidelines with regards to how you image these patients, and with the development of a lot of new therapies for M1 CRPC patients, I think there was clearly a need for something like this.

That was published in 2014, and then that was followed up two to three years later with the RADAR II, which introduces this idea of therapeutic layering in prostate cancer. What's most exciting right now is RADAR III was just accepted by The Journal of Urology. The title of that article is “The Clinicians Guide to Next Generation Imaging in Advanced Prostate Cancer." It's a multidisciplinary group of authors that provides recommendations with regards to how we integrate all these new tools into our clinical practice.

We break it down into those three different buckets again, that we did in RADAR I. We have the patients who are newly diagnosed with prostate cancer. We have those patients with biochemical recurrence, and then we have those patients with M0 CRPC. I think when we hear about all these new imaging techniques, I think it gets really confusing, and  there's no real consensus with regards to how we do things. There are a lot of geographic differences across the world, and I think that's confusing for a lot of our practitioners out in the community.

To me, this level sets. This provides distillation of all the different data that's available. It provides, just sort of, expert recommendations with regards to how you should image.

Dr Alicia Morgans: I think that's exactly what we need. We need to get everybody back to a level baseline so we know where to start, particularly as we're trying to interpret clinical trial data that's based on standard bone scan, CT scan imaging. It's really complicated for us, in clinical practice, to think about how to integrate the PSMA PET that we might have on our patient who happened to travel here, who knows where, and get this scan. So, what kind of recommendations or guidance does RADAR III give on that? How do we think about imaging in that situation? 

Dr Phil Koo: Sure, so you bring up a great point about clinical trial data. The clinical trial data, with regards to Next Generation Imaging, currently is focused more on detection, and change and management. Clearly, based on a lot of different studies, there is a significant change in management. When you look at Axumin fluciclovine, you have the LOCATE trial and the FALCON trial, which show 50%-60% significant change in management. We see similar data with the PSMA. So, you know, that's great, but again, what we really need to shoot for is changes in outcomes.

Dr Alicia Morgans: Yes.

Dr Phil Koo: But, we're not there yet. For the time being, our recommendations are for patients who are newly diagnosed with prostate cancer. Low-risk disease, obviously you're not going to image those patients. Patients with intermediate to high-risk disease, that have negative standard imaging, maybe you'd want to consider Next Generation Imaging, if you as a clinician, have a continued high suspicion for metastatic disease. I think there's so much value in the physician/patient relationship, and knowing when something's wrong. There are things that you're going to know based on the path or the presentation that really just makes you wonder that this patient really does have that MET that we're not detecting somewhere. In those cases, I think it might be worthwhile to pursue Next Generation Imaging. 

Biochemical recurrence is sort of where the money is, currently. You know, whether it's Axumin, PSMA, that's where we have the most data, and that's where I think, if you haven't used these Next Generation Imaging tools, this is where you should start. For biochemical recurrence, we recommend considering Next Generation Imaging when the PSA level is greater than 0.5. A lot of data shows detection rates with the PSA level is greater than 0.5 or greater than 1, to be actually pretty good, maybe in the 60%-70% range. Some would argue maybe you could even do it at lower PSA values. There are some data out there that shows that even at lower PSA values, PSMA can detect disease. So again, we sort of leave that up to the individual, with regards to their own practices. 

For M0 CRPC, that's an interesting topic right now. At GU ASCO, obviously we heard about PROSPER and SPARTAN, and that sort of through a change in a lot of the way that we had to think about imaging in that space. In the past, when we had nothing for M0 CRPC, it made sense to do bone scans and CTs, or even Next Generation Imaging, to detect that metastatic lesion, to get them approved for some of these newer therapies. With PROSPER and SPARTAN, I think, I would argue that Next Generation Imaging probably doesn't have a role, now that we have these therapies, at least Apalutamide, that is approved for this space.

So, for advanced disease, there really is no role for Next Generation Imaging because the role of Axumin or PSMA, with regards to treatment response, hasn't been established. That being said, in RADAR III, we do introduce the idea of using some of these Next Generation Imaging tools, if you want to know if they've really grossly progressed. If something's wrong, and the other imaging tools aren't documenting this, this might be able to help detect new osseous metastases and whatnot, that will help prove that this patient is progressing. There's limitations with that because you're comparing Next Generation Imaging tools to traditional tools, but I think, you know, we're going to need to learn more about this. We sort of put it out there as an area that I think we should explore in the future.

Dr Alicia Morgans: I completely agree, and I appreciate that you and the team took the time to write these recommendations down. I think with the new drugs available, particularly in the M0 CRPC space, there's, I think, probably an eagerness to use these drugs, and also an eagerness to use these really novel, exciting imaging techniques. It doesn't make sense if you have a patient with M0 CRPC to do things like a PSMA PET to find metastatic disease, if the studies weren't really designed with that imaging in mind. I particularly appreciate that, that the team was able to address that as that is really cutting edge, and incredibly timely information. Of course, the use in biochemical recurrence hormone sensitive setting is really useful, and thanks for the comments in the advanced disease.

So, I think in addition to that, one of the things that we struggle with in clinical practice is our understanding of these PET probes. So, PSMA, we use it sort of as a basket or a catch all, but there are different types of PSMA targeted agents. Some are therapeutic and some are diagnostic, and I'd love to hear more on that, and I'm sure the listeners would like to hear more, too.

Dr Phil Koo: So, early on when we talk about these PSMA probes, I think the biggest thing is just increasing awareness about these new imaging agents that are available. Behind the scenes, from the imaging perspective, we know that it's just a class of a drug. It's a class of a radiopharmaceutical, and within that class, there are many different subtypes that have very subtle chemical differences that can change the physiology and the output of these tests. Take, for example, PSMA that's been studied, Gallium-68, for biochemical recurrence. That's something that we've heard a lot about, but for primary disease, there's actually an F-18, a fluoride compound, that has a longer half-life, that's been studied more in the primary setting. 

There are subtle differences. That difference between fluoride versus Gallium, really impacts the deliverability of these radiopharmaceuticals. Gallium has a half-life of roughly one hour. Fluoride had a half-life of roughly two hours. That changes the commercial aspects to these drugs as well. Moving forward, we're going to need to think of these different radiopharmaceuticals as drugs, and we're going to need to be ordering specific drugs for specific clinical situations. It's no longer going to be this idea of, let's get a PET CT, let's get a CT, let's get an MRI. It's, let's get a PET CT with a specific drug to answer a specific question. I think we need to be very smart about this.

I agree with you completely that we cannot just be imaging patients, willy-nilly, left and right, without really having a purpose in mind. So, just going back to RADAR III, that's another important point that I want to make is, whenever we order these tests, we need to be prepared to take action based on these results. So, our recommendation to the readership is, before you order this test, make sure you understand that what you're going to do with the output of these tests. If you see oligometastatic disease, what are your plans? If you see nothing, what are your plans? If you see diffuse metastatic disease, what are your plans? If you have indeterminate findings, what are your plans? The last thing we want is for people to get these exams, and for it not to impact what they're going to do for our patients. 

It's a very exciting time. I think there's lots of confusion. Moving forward, you're going to see more discussions about what each individual PSMA subtype is, and what it does well. That's going to lead into this idea of therapy. That introduces the field of theranostics, where you can buy therapy with diagnostics.

So, if you have a PSMA agent that can confirm that the patient's prostate cancer is PSMA expressing, then it gives you some reassurance that if you do put a therapeutic radiopharmaceutical onto that, that it will kill those cells that are expressing the PSMA. I think this important because what we know is that maybe 10%, or maybe even 20% of patients with prostate cancer don't express the PSMA receptor. So again, that theranostics approach will help us be a little more selective with what patients we treat. 

Dr Alicia Morgans: Absolutely. Thanks so much for reiterating. As a radiologist, it's great to hear someone say that we don't order scans just to order scans. We order scans because we're going to make a therapeutic decision or help understand a patient's prognosis and counsel the patient, or whatever our reasoning is. We have to act upon the results of that scan. We're not just ordering a scan to see a pretty picture. I think that's really important to drive home. 

At some point in the near future, I hope we can talk more about the theranostics, and about ways that we're using PSMA targeted therapeutics, like Lutetium and others, to potentially really alter disease course, and treat some patients who have incredibly refractory disease. That's a really exciting area, too. 

What is your take home message for the listeners? 

Dr Phil Koo: My take home message is, if you're practicing in the United States, and you haven't used these advanced imaging tools, most likely Axumin, because that's the only one that's FDA approved currently in the U.S., I recommend that you try it. It's here and it's here to stay. These new tests aren't going away, so we need to figure out how we incorporate it into our practice. I recommend that you reach out to your radiology group, find your go-to person for nuclear medicine, find your go-to person for therapies, find your go-to person for prostate MR, and really build your own, sort of, internal network of experts, so you can really advance the care for these prostate cancer patients.

I think there's a lot of new advancements on the diagnostic side. There's advancements on the therapeutic side. We had Radium 223 over the past few years. That's going to continue to grow. We have new therapeutic radiopharmaceuticals coming down the pike, so I think that's going to be a huge part. I encourage people to just figure out ways to make this work. I do strongly believe that this will improve the care. All the data that we have so far is showing that, but we need more data that shows that it will change outcomes. That's where my other request is, I think we all need to continue to work together to design those trials, design those registries, that really capture that data that shows the impact of these radiopharmaceuticals on outcomes.

Dr Alicia Morgans: Absolutely. So, I appreciate talking with you, and it's quite a time of hope with a lot of advances, and a lot of work to do, but we're really making some progress. I appreciate you helping walk us through some of these things.

Dr Phil Koo: My pleasure.

Dr Alicia Morgans: Thanks so much for your time.

Dr Phil Koo: Yeah, thank you very much. Glad to be here.