Alicia Morgans: Hi, I'm so excited to be at ASCO 2022 with Dr. Ashley Ross of Northwestern University, where we have the opportunity to speak about Decipher testing, both Decipher Biopsy, and Decipher for prostatectomy specimens and how we integrate that into standard clinical practice. Thank you so much for being here.

Ashley Ross: Thank you for having me.

Alicia Morgans: Wonderful. So Ash, I know you've been involved with Decipher for a long time, using it in clinical practice and actually working on a lot of trials and investigations to better understand how we use the data from the Decipher test to really inform our practice. Decipher's actually used in another setting though. Decipher Biopsy is something that you can use even before a prostatectomy. How are you using that test?

Ashley Ross: Yeah, so traditionally, the next thing that they moved into was a big decision making about who should we do active surveillance or not. And a lot of us were using genomic tests, and there was multiple tests in this category, Decipher, Prolaris, Oncotype DX Prostate, that was helping us decide who with higher volume, low-risk disease or with favorable intermediate-risk disease was an appropriate candidate for surveillance. For all of those, if the genomics were in the higher risk category, so the RNA expression of the cancer was showing metastatic potential or potential for adverse pathology, they probably should not be on surveillance.

More recently, particularly with the genomic classifier and Decipher, there's been intense investigation into intermediate-risk prostate cancer. And there, if we're going to treat someone with unfavorable intermediate-risk disease, or even with high-risk disease, for surgery, our treatment doesn't really modulate much. We're going to do surgery. And if you're taking someone in the operating room because the disease has risk, in most cases, we're going to perform a lymph node dissection.

So the question is, well, what if you don't do a mechanical therapy? I often tell my patients, surgery is like a weed in your garden. You're going to pluck the prostate cancer out like pulling a weed out. But radiation is like you're going to spray it with weed killer. And we're really good at targeting the radiation. We can spray it in the right place, but will that weed die with that weed killer? Is it going to be sensitive to the radiation? Does it need more to kind of sensitize it? And androgen deprivation therapy may be sensitizing to that radiation, but it has morbidities even with the newer androgen deprivation therapies that are out there like relugolix, it still can have lingering effects. It can affect bone health, sexual function, metabolic health, obviously.

So the idea is what if we have another tool like genomics, with Decipher, for example, and we can risk stratify men even more and decide who's going to do well with radiation alone, who's going to need the androgen deprivation therapy. And there's been studies, both retrospective series from databases and also now evaluation of prospectively collected data in clinical trials that have shown that if you have a low Decipher score and you have unfavorable intermediate-risk disease, if you get radiation by itself to that patient, they do quite well, good metastasis-free survival, good overall survival from the RTOG 0126 trial. And so that actually means two things. Right now in my practice, I'm a little bit ahead of the curve in the sense of I'm using it to decide, do I add the ADT or not? Index patient would be the 70 year old, maybe with a little bit of cardiovascular history, has four plus three equals seven cancer, but maybe in a few cores, PSA is under 10, T1c exam.

And the question is, do I add on androgen deprivation therapy for six months or just give them radiation alone? And then I'll get the Decipher. If Decipher's low risk, I think they do quite well with just the radiation. If the Decipher's high risk, I think they really need the ADT to do well. And there was almost a fivefold difference in metastasis-free survival from Decipher low risk to high risk in that context, if you didn't give the ADT. Now, some people say, "Well, I think that that's okay in certain cases. I really want to see that in randomized perspective data." And the National Radiation Oncology Group has been very proactive in that way. They've just opened, at multiple sites across the US, the GUIDANCE trial. And that's actually saying two things. One, stratify unfavorable intermediate-risk by Decipher. If you're Decipher low-risk, you can get ADT for six months or randomized to just radiation alone.

And also importantly, there's some data from Paul Nguyen and others that shows that for some of these guys who in favorable intermediate-risk with high Decipher, they have poor outcomes even with the six months of ADT. And so the other arm is if you're high Decipher, ADT for six months plus the radiation, which is now standard of care, or six months of ADT plus darolutamide. And that would be interesting to see if that improves outcomes like metastasis-free survival.

On the higher risk case, there the question is, do we really need 24 months of ADT? If the Decipher is low, can you get away with less, 12 months? And I have to say, in my patients, I really do see a difference between 12 months and 24, particularly some of the cognitive and psychological effects of the ADT. I see that as a point. And then for the high Decipher risk, high-risk guys, is that enough? Do they need intensification with something like abiraterone or apalutamide? And that's being studied perspectively in the PREDICT-RT trial, also opened at multiple centers. And so it's really becoming a big part of my practice across spectrum. And I think that as those trials evolve as more data develops, I think... A lot of us are using it routinely. I think it's going to become, quite frankly, a needed standard of care, but we'll see how those trials shake out.

Alicia Morgans: Well. That's wonderful. And we'll have to make sure that we have links to those trials available for folks and the clinicaltrials.gov information because the NRG is really doing all that they can to help us answer these questions of how we can apply the treatments in a way that's not one size fits all. Because even though we try, as you said, to talk about favorable or unfavorable intermediate-risk, and then of course, high-risk, we know that these patients don't have disease biology that puts them in such sort of large buckets. So this is fantastic.

Ashley Ross: Absolutely. And there's always a question I ask myself sometimes, and sometimes I talk to colleagues about, which is, if you look at those trials, and thank you for putting the links in for the audience, they're really pragmatic trials. They're things that we're doing right now, but they want to make sure we're doing it the right way, and so they're studying it. And the question is, do we pull the trigger on these things in our practices? And I think that what the index patient I was talking about maybe demonstrates is, for a lot of us, we're not ready to routinely use it on all patients until the trials come out. But there's certainly patients, and it might be even a quarter of our patients or more, where we really are at a crossroads of what exactly do we want to do to them.

And like you said, having more personalized medicine allows us to make the decision. Feel free to comment as well, that in my practice, it's like, where are you practicing? Are you reactive to the data that's coming out and waiting until it's fully finalized, or do you think that there are places that you can be a little bit ahead of it and use the tools that we have because they're available before you know the full answer? I think that the latter is what I do, particularly with the patients where I'm struggling a little bit. I'm not sure how you approach it, but...

Alicia Morgans: Yeah, I think the same exact way. In my current practice, I actually see a fair amount of patients with localized disease, and we're using these kinds of tools all the time to try to make those decisions, and of course, to enroll patients in those NRG trials, because those are so important as well. So if you're in your practice and you don't feel comfortable making the choice based on the score alone, it's really, really helpful to know, hey, right down the street I can send patients who are going to get radiation to this trial. You may be able to even be a site to provide the ADT, if that's possible within the trial context. But really giving patients the opportunity to enroll in those trials is wonderful, so I appreciate you raising them. And I also appreciate you talking us through these really nuts-and-bolts, concrete examples of how we can use these tests to do the right thing for our patients. It's extremely helpful.

Ashley Ross: Thank you.