Paul Nguyen: Thanks so much for having me, Zach. I'm really excited to be here.
Zachary Klaassen: Always good chatting with you. Today we're going to be discussing the Artera AI prostate test specifically for post-radical-prostatectomy BCR. So, before we get your thoughts on this, maybe just level set for our listeners, what exactly is the Artera AI prostate test? What is involved in coming up with the score that we've become very familiar with over the last couple of years?
Paul Nguyen: Yeah, thanks, Zach. It's a very poignant time to be talking about the Artera test. It was founded by all of our dear friends, Felix Feng, UCSF, radiation oncologist extraordinaire who passed away almost exactly a year ago to this day. He passed away December 10th, 2024, way too young. And so we miss him so much. But what a gift he's left us in terms of a legacy of this incredible test, the Artera test. And it was Felix who had the vision to put together clinical factors that we all know about, PSA, T category, Gleason score with digital pathology images. And what they do is they take a picture of your biopsy, or in this case to take a picture of your prostatectomy sample, and they digitize it, and they run it through their AI algorithm. They've created a score that predicts for outcome, and they put that together with the clinical variables, which makes the score even more robust. And then that's the Artera classifier. And it's a combination of clinical factors, and AI applied to digital pathology slides.
Zachary Klaassen: Yeah. And it's really taken us by storm over the last couple of years, as I mentioned. And the data we're going to talk about today is basically from 18 months ago, AUA 2024, Todd Morgan presented the first data. Now it's available commercially. Maybe just pull up a couple slides. You going to show us basically the high level results which Todd presented to AUA.
Paul Nguyen: Yeah, sounds great. So, yeah, I'll pull up the slides, and while I'm getting that up, I'll just say what the study was. But we already have, Zach, as you well know, the Artera tests for biopsies where they looked at patients with intermediate-risk prostate cancer, and they could tell who needs hormones, who doesn't, and who's going to do well, and who won't. And so here the test is trying to look at the post-op space. And just like the initial test, they developed it in the exact same way. They looked at samples from the RTOG/NRG cooperative group, and there were two post-op trials. One of them was RTOG 9601. This was a study of post-op salvage radiation with, or without two years of bicalutamide. And then they looked at RTOG 0534. This was also a post-op study looking at salvage radiation where either you radiated the prostate bed, or you had prostate bed radiation with hormones, or you did prostate bed radiation, hormones, and pelvis. And they used these, they divided it into a 70% derivation cohort, and a 30% validation cohort.
They combined the clinical factors in the derivation cohort. They came up with their model, they locked it, and they aimed that model to have the biggest split in the survival curves predicting for distant metastasis. And basically they had 40% of the patients in the high-risk group, 60% of the patients in the lower-risk group. And what they found is what I'm going to show here on the screen, which is really an excellent discrimination in terms of outcomes between the low-risk, and the high-risk patients. So, what you can see on these slides is when they compared MMAI high versus low, it was very prognostic for distant metastasis. So, here you see in blue, the MMAI low. And these patients, as you can see at five years, they had a 4.1% risk of distant metastasis compared to 10.8% for the MMAI high. And when you went out to 10 years, it was even much more of a separation in the curves, 8.7% versus 27%. So, this was fantastic at differentiating less-risk patients versus higher-risk patients.
But here was the other thing that was really cool, and this was the same thing that was cool about their intermediate-risk test, was that they found that when you applied it to the question of did these patients benefit the same from hormones, it was very different, meaning that if you were MMAI high, it appeared to make a big difference if you got hormones, or if you didn't with your radiation, these were the estimates of distant metastases. You can see it's much higher if you didn't get hormones than if you did. Whereas if you were MMAI low, they couldn't really see much of a difference. I don't mean to say there was no difference. If you look at the numbers, there was still a little bit of a benefit, 10.3 versus 7.8% here. And I think what they said in the paper was there was a big difference in the number needed to treat, that with the MMAI high, the number you needed to treat was something like five to prevent the distant metastasis, whereas in the MMAI low, it was something much higher like something in the 20 to 40 range. So, big differential in terms of the benefit for hormones. So, yeah, those were the two findings in the study.
Zachary Klaassen: No, that's fantastic. And I think when we look at the conversations we have with patients, and you, and I both talked to localized patients, whether they're in the primary setting, whether they're in the recurrent setting, these can be long, and challenging conversations of time, because we want to make sure we're giving our patients the full shared decision-making when we're discussing options. So, I'm going to put you on the spot a little bit. Let's take the patient, they're coming to you for salvage radiotherapy, we've sent them over to you. They're an MMAI low-risk patient. How are you having that conversation as to what to expect, and maybe what their options are?
Paul Nguyen: Yeah, it's such a tough situation, Zach. And I say, I feel it in my heart because for some of these guys, some of these guys are young, and we all know this is going to be their last chance at cure. And so on the one hand, for sure, we want to think about, okay, what can we do to maximize the chance of cure? But on the other hand, as we all know, man, these hormones can really affect their quality of life. And I would say for some patients, they come to me, and they're going to be like, "You know what, doc, I just want the hormones. I don't care. Just give me the hormones." But for some patients, they really want to know, "Do I really need these?" And I think this is where this test is really going to come in handy because here we can quantify it for them. We can say, "Hey, maybe you'll benefit, but this is probably the magnitude of that benefit, and is this worth it for you?" And I think for these MMAI low patients, that's going to give you a reason to think about omitting the hormones, and maybe still be able to sleep at night as a provider that you're not doing the wrong thing for your patients.
Zachary Klaassen: No, absolutely. And we'll flip the script. Let's say somebody comes in, whether they're for, or against hormones again the MMAI test, post-radical-prostatectomy, BCR, talking about salvage radiotherapy, but they have a high-risk test. So, now how does that conversation go? Are you able to not sell it, but position the hormones as we probably should do this?
Paul Nguyen: Yeah, I think, and I've had this experience with my most reluctant patients. When they see data that shows a gap this big in outcome, it's really hard to argue against that. And you know what? It gives them peace, too, because they're like, okay, this is going to stink in terms of quality of life, but if it's going to make that much of a difference in my survival, or my metastasis rate, I'll do it.
Zachary Klaassen: No, absolutely. I think we talk a lot about precision medicine, and this really is sort of helping us in this disease space, which has really had... These are difficult conversations, as I mentioned. I mean, I think starting someone in hormones, they don't know what they're like till they're on them. I think this can really sort of rationalize why we're deciding one approach versus the other. Paul, I want to ask you about, from a radiation oncology standpoint, this is going to be huge for you guys, I'd imagine. How is this going to fit into your workflow? How do you anticipate ordering the test, talking to the patients, how long is it going to take to get the data back, et cetera?
Paul Nguyen: Yeah. I mean, what I've found with the MMAI in the intermediate-risk space, it's really fast. I mean, the rate-limiting step is getting the tissue to Artera, but once they get it, they turn it around super fast. They have a portal, that part is super easy. So, I've found it can be as little as 10 days if everything works out fine. And most patients for an important decision like this, they're happy to wait for that test to come back. And so I definitely see myself ordering this test quite a bit for my patients I'm going to be seeing for salvage radiation.
Zachary Klaassen: Awesome. This has been a great discussion, Paul. As always, good chatting with you. Anything we haven't hit on, anything coming down the pipeline, take-home messages for our listeners?
Paul Nguyen: Yeah, I mean, I think we talked about a lot of the practical aspects. I do want to make a plug for a trial that I'm very excited about, and I'm just going to share the slide if you give me one second.
Zachary Klaassen: Yeah, absolutely.
Paul Nguyen: Okay. So, I want to make a plug for the Prostate IQ trial, which is the first trial that's coming out, randomized trial using this exact Artera post-op classifier. And it's led by Dr. Karen Hoffman at MD Anderson, as well as Dr. Marisa Kollmeier at Memorial Sloan Kettering, and we're participating as well as a few other sites. And the idea is in the post-op setting, the patients are going to get stratified by the Artera test. If they're Artera low, then they get randomized to six months of traditional hormone therapy versus six months of apalutamide. And the hypothesis here is that maybe the six months of apalutamide monotherapy is going to reduce the side effects. And on the Artera high side, or patients that have a PSA greater than 0.5, or who are really aggressive clinical node positive, or pathologic node positive, arguably the standard for those patients has moved to 24 months of traditional ADT with salvage radiation.
That was what was shown in the RADICALS HD trial. And so they're getting randomized to that versus a shorter, more intense regimen, which was very similar to what was used in the FORMULA 509 trial, which is six months of ADT plus apalutamide, hoping that maybe you can use a shorter regimen, but more intense in order to reduce side effects. So, pretty excited about the study. It's a way to use the test to try to risk stratify patients into different arms. Now, obviously everybody on this study is getting hormones, and we know that for some patients with Artera low, they're going to use that to choose not to get hormones. And I think that's totally reasonable. And this study is really for patients where they're going to want the hormones anyway, and how do we risk stratify them a little bit better? So, look out for this trial, and the results in a few years.
Zachary Klaassen: No, absolutely. And I think we're seeing so much more of these biomarker-driven trials in terms of stratification, so this definitely fits into that. So, we'll definitely have you on when these results come out. And certainly the last call that I'll make is the paper, the data you were citing for the prostate post-radical-prostatectomy with BCR is going to be in European Urology. It's in press now, so we'll look for that to be published shortly. And Paul, always enjoy chatting with you. Thanks so much for your time.
Paul Nguyen: Thanks so much, Zach. Yeah, shout out to Todd Morgan, the first author, and Dan Spratt, the senior author on that paper, and really appreciate your time.
Zachary Klaassen: Always. Thanks, Paul. Paul Nguyen: Take care, Zach.