The Use of Genomics in Unfavorable Intermediate-risk Prostate Cancer - David Morris

December 20, 2022

David Morris joins Ashley Ross in a conversation on genomics in prostate cancer specifically, in the unfavorable intermediate-risk patient. Drs Morris and Ross highlight the use of genomics in decision-making when considering what the best treatment option is for this group of individuals. They are particularly interested in determining if any of these intermediate-risk patients might actually be higher risk or lower risk than expected. 


David Morris, MD, FACS, President, Urology Associates, PC, Nashville, TN

Ashley Ross, MD, Ph.D., Associate Professor, Department of Urology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois

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Ashley Ross: Hi and welcome everyone. I'm Dr. Ashley Ross. I'm a urologist at Northwestern Feinberg School of Medicine. I'm really glad to be here with a friend and colleague, Dr. David Morris. He's the President of Urology Associates in Tennessee, and an expert in prostate cancer.

What we're going to talk about tonight is, genomics in prostate cancer. Specifically, in the unfavorable intermediate-risk patient. Welcome Dr. Morris. Thanks for being here tonight.

David Morris: Thank you.

Ashley Ross: Genomics have become a bigger and bigger part of our routine use and practice, certainly in the guidelines, certainly in my practice. When you think about localized prostate cancer in your practice, how are you using genomics for your decision making?

David Morris: Sure. I think that the earliest kind of low hanging fruit was active surveillance patient identification. But I think we've hopefully moved, maybe not as far as we should go, but certainly, the people that are going to take it up have taken it up to help identify AS candidates. And I think, the next frontier for most of us is, trying to really pick out the medium-risk patient if they're kind of a wolf in sheep's clothing, higher risk or lower risk in the intermediate range. I think the high-risk patients, there's some potential benefits down the road with predictive markers, but I don't think we're really there yet. I think the bread and butter sweet spot right now for most of us, is choosing who intensify therapy and who to withhold therapy.

Ashley Ross: I think, most of our listeners would know, but for the man with unfavorable intermediate-risk cancer and about a 10 year survival, what are the different treatment options that they are typically looking at?

David Morris: Even just today, I think the standard conversation with a patient with that is, "You have a real cancer. You very likely need therapy." Surgery and radiation, it's a personal choice. A side effect management, and potentially their history may push you one way or the other, with avoiding symptoms, or something along those lines. But I think, the real question for me is, if someone is leaning towards radiation therapy, is it somebody that we need combination or multimodal approach? I think with surgery patients, the answer's fairly easy. If you have surgery and have a recurrence, you're probably getting something else. But for radiation, it's more of an upfront question of, can I identify somebody that needs extra hormone therapy? Can I identify somebody who may be able to forego hormone therapy and the side effects of hormone therapy? And radiation may be enough.

Ashley Ross: Yeah. And to your point, I think that, what the man needs to be thinking about, is it surgery versus radiation, or is it surgery versus radiation plus androgen deprivation therapy, as you mentioned? And as you said, the genomics before were telling us, well, who's at risk of reclassification for surveillance? And if they're at high-risk, we wouldn't survey them. Now we've seen some data over the last few years, looking at genomic scores, particularly the Decipher score, in unfavorable intermediate-risk patients.

Recently, there was a clinical trial that they did a retrospective evaluation of, and that looked at people in different buckets. It was like, either you have a low Decipher risk and you do pretty well with just radiation alone. And then, or you have an intermediate or high Decipher risk, and it showed that all the events of metastasis and stuff, if you've got radiation alone, that's where they were occurring. And so, I'm not sure.

In my practice, I've started to use the Decipher in that way. That was the RTOG 0126 study. I've started to use Decipher in that way. There is a national NRG trial perspectively going on, that's actually testing, do these decisions, are they the right decisions that you're making. But how have you used it in your practice? Have you started to look at your unfavorable intermediate-risk patients, and use it on all of them selectively? How do you go about doing that?

David Morris: That's a great question. I think what we're doing is, using the Decipher postop tests for prostatectomy specimens, and just moving it more into the front-line biopsy situation, where the postop test is very good at helping to identify, potentially, patients that may benefit from additional hormone therapy with their radiation, or more intensification. And so I think, that idea on the front end is now, can we identify patients who may need additional hormone therapy along with their definitive radiation? And so, it's certainly something very lowest for prostate cancer. I very rarely order, or would not encourage my partners to order a genomic test. I think the answer with clinical factors is probably enough. And you could probably make the argument for very high-risk patients, that they very often do not need anything up front to help them guide their treatment decisions.

But in the middle, there's just a lot of gray area on, no hormones, six months of hormones, 18 months of hormones. Is hormones with ADT monotherapy enough? Do we need to be doing even more if somebody really has high-risk features? So I think, that's probably the area that's seen the fastest growth in the intermediate-risk, is trying to answer a different question than just surveillance or not. It's really just, if we are going to treat you with radiation, how much hormones is the right answer.

Ashley Ross: Yeah. And right now, what I tend to do, and I was a little bit of an early adopter, but I tend to hedge a little bit. So for example, if I have an older patient who I've diagnosed with unfavorable intermediate-risk prostate cancer. They have a 10 year survival, but just that, and maybe they have some cardiovascular risk factors and some other factors, and I worry a little bit about the ADT. That's an ideal patient, where if you have a little bit more prognostic information, you can tease it out.

Obviously, I think until the prospective trial is complete, for the 61 year old patient, who just never wants to be in incontinent, doesn't want to do surgery, but has 4-3-7 in four cores, even if their Decipher looks okay, I lean a little bit towards the radiation. So it's a little bit of a hard choice.

Now, I've had a lot of different experiences. But in your experience, how does the workflow go? Are you usually making the decision about the hormonal therapy or not? Or are you sort of packaging and consulting the patient, and then sending them to the radonc with an idea of what they're going to get in their head?

David Morris: Academic centers are a little different than every private practice center. We are not an integrated network. I don't have a radiation oncologist within my group. Many large groups do have a radiation oncologist. But I'd say, the vast majority of urology happens outside the four walls of urology, that they're sent to the radiation oncologist. And honestly, I think we need to own this more than the radiation oncologist. If you ask them what a Decipher score is, most of the community radiation oncologists will say, "I have no idea what you're talking about." Unless they've dealt with a urologist who tends to order it and make sure that they're aware of the answers.

So I think that, I typically broach the topic of ADT and the duration of ADT with the patient on the front end, and actually put it in my note with the consult referral to the radiation oncologist of, I'm leaning towards definitive radiation with a short course of hormones, Decipher is pending, or Decipher is back. And therefore, we're thinking maybe, potentially avoid hormone use in this patient. I tend to at least suggest it, and then want their buy-ins, that we're getting two voices that are saying the same thing. And if they strongly outweigh me, then I'm willing to say, "Look, they're the experts of radiotherapy, and if they really feel like they need the definitive hormones on top of it, then I'm okay with that." But at least, I can provide some guidance to the radiation oncologist. Because I think they're not the ones typically ordering these sort of tests, they're ordered from us at the time of biopsy, or shortly after the result is back from the biopsy.

Ashley Ross: Yeah, I agree. And I think that there's, obviously, there's lots of radiation oncologists out there that do do that. And even the ones in the community practice I've had, there's a spectrum obviously. But like you mentioned, I think it's important to at least give your full thoughts on, do you think ADT is necessary or not? I even now, have started telling them what type of ADT I'm thinking about, and what duration. Some of the radoncs prefer, I'm sure you've seen this, prefer that we give the androgen deprivation. If it's necessary, some of them prefer to give it. And I do think it starts in the practice.

Now you lead a, I think it's a huge team. I don't know how many of you guys there are across your whole network. But how do you guys go about disseminating new knowledge? There's obviously, great podcasts like this that could help with that, but how do you counsel your team, or what do you guys do internally?

David Morris: Well, so a lot of it's internal email education. The days of having giant group get together dinners were certainly difficult for the last two years. And we're just now getting back to that sort of educational platform. We don't have a very formal like monthly grand rounds, but some of our best attended, and probably highest reviewed educational programs, have been when we've had a joint program with our local radiation oncologist, and our urologists who treat prostate cancer. We've also had some that are with our medical oncologists for more advanced disease, with some of the urologists that are making the referrals. Because that just irons out some of the referral processes, and makes it much more concrete about what are you looking for? What would you like? And then, they understand that we're not just ordering the test willy nilly, that there's a question that we're trying to answer. And that, if we send it to you, it's because we value that.

And then honestly, sometimes they're just not aware of the data. They know all the NRG and RTOG trials. They don't always know the genomic kind of analyses that go piggybacking on top of those trials. And so, sometimes when you say, "Look, you know this trial." This analysis basically allows us to try to pick out the best patients of that group who've got the most benefit, and those are the ones that we really want to target.

Ashley Ross: Yeah. And I think that, it was nice to see the NCCN really basically said that this is about risk stratification. There's independent prognostic information here. You could risk stratify, and that might help you make a decision. As you mentioned for, I think that the radoncs do tend to be very data driven. And the NRG trial that we were talking about, which is called the GUIDANCE trial, it's opened at multiple sites across the US, is basically taking unfavorable intermediate-risk prostate cancer, doing a Decipher. If your score is low, you get randomized to just radiation alone, or radiation plus hormones. If it's high, radiation plus six months of ADT, or radiation plus intensification of systemic therapy.

That trial's going to take a while to report out. You know? And like you were mentioning, right now, routinely you use the genomics in your clinical practice for surveillance. There, we're just seeing the music consortium give their data. We're just seeing some of the clinical trials with surveillance coming out. And so, the question is, how much, how free do people feel, to be a little bit ahead of the curve with it? And I'd be curious, as for you, how do you decide when you want to adopt something? Or do you see these things as tools? And if the tool has enough evidence, you'll use the tool with your clinical acumen until you get there.

David Morris: I think it tends to be the latter. Honestly, if you wait for the AUA or NCCN to have it fully written in the guidelines, you're going to be waiting forever. And if you've educated yourself on the data points, the trials that you value that accrued well, that seem to have good balance. And then, you can present that to the patient and make a shared decision, it's really kind of up to you and them to value, is that a test that sounds reasonable? It would be no different than saying, "There's inner observer variability on pathology, Gleason scoring. Do you want to trust this pathologist?" And having them say, "Well, that's the one you trust every time, then sure. I'm going to trust that pathologist." I don't have a problem pushing the curve, as long as you do it in a cost conscious manner.

I certainly don't want to order every test available. But if you have a good question, and you think that, that test is going to actually provide an actionable bit of information, I think you could support ordering. And the guidelines are moving in that direction. If you're really going to use it, order it. But if you certainly have had the conversation with the patient, and you can look at that patient, and they're barely at 10 year survival, and they're a cardiac cripple. And you're thinking, "I'm probably not going to put them on hormones no matter what." Then you probably don't need the test.

Ashley Ross: Yeah.

David Morris: So I think that, that's the clinician side of... The guidelines are guidelines. If you're 100% following guidelines, you're probably not practicing very good medicine. So there's a little bit of the art there, that allows you to order tests that have value in certain situations. And I put that in that, this test specifically, in that bucket.

Ashley Ross: And I think, one thing that I thought has been nice is, as we get more and more into precision medicine, using genomics across the spectrum, it does allow for, particularly where there are questions, not just implementation of more therapy, but deimplementation. And that's what I really like about, some of this risk class stratification is that like, it can save a lot of cost and morbidity to the patients. But if they need the extra treatment, then that obviously, also saves them long term morbidity from their cancer progression.

David Morris: There are multiple trials with lots of hormone use that show benefit. But then, when you get in the weeds, it's for a subset of patients. And you think, "If I just accept that for everyone, there's a lot of patients that I have on therapy, that probably are getting worse from the therapy, instead of better."

Ashley Ross: Absolutely. And I think, if you look at a lot of those trials, the absolute reduction in outcomes is often quite minor. And overall survival is often not met because of the nature, and that's probably where it's most important.

Well, thank you. It's a great discussion. Thank you very much for being here tonight. And hopefully, for our audience, I think that it's, as you get more used to more of these tools that are out there, very widely available, and hopefully you're looking at them, at least understanding what they are in your practice. And if not, maybe some of this discussion has helped you get further along with that.

Ashley Ross: Thanks again.

David Morris:
Thank you.