Eric Kim: Hello, everybody. Eric Kim here, chief of urology at University of Nevada, Reno. And we're lucky enough to have Dr. Aaron Berger, who's the CMO of Associated Urological Specialists. And that's in Chicagoland, I believe.

Aaron Berger: That's correct. We cover the south-southwest suburbs of Chicago. Good morning, everyone. Thanks for the invitation to be here today.

Eric Kim: Today, we're going to talk about treatment intensification for high-risk disease as well as biochemical recurrence. So, Aaron, for high-risk disease, just to start off with something very straightforward that probably everybody has dealt with, is there a way that you decide between surgery, radiation for the high-risk patient?

Aaron Berger: Yeah, that's a great question. Obviously, it's always a patient to patient decision. I think for those high-risk patients that maybe are younger or have other voiding dysfunction, other issues that where maybe their prostate just being removed is the right option, certainly, it's always an option, I guess is the right answer.

But I think that with a lot of data out there for high-risk patients in terms of the radiation literature comparing it to surgery, I think it's-- the argument to say you have to have surgery has become a little less compelling.

Maybe for those fairly younger patients, I think it's certainly still beneficial to have that discussion. But most of these patients we're seeing are in their 60s or 70s. So I just I don't know if kind of pushing surgery as much as maybe we used to is really the right answer. But having a balanced approach, saying here's the options, potential side effects, risks, all that kind of stuff is obviously important for all patients.

Eric Kim: Yeah, no, I think you're absolutely right. I think you hate to be the one that thinks that cutting is the only answer. And then you also hate to be the one that almost like a nihilist, you say, well, you have such high-risk disease, you're going to end up with radiation anyway. You may as well just get radiation. You kind of hate both answers because it's not very nuanced. Like you said, it's a patient to patient decision. And we should try personalize our treatment when we can.

Aaron Berger: Yeah, and unfortunately, sometimes patients will say, well, what would you do? And that's always-- I'm sure you get that, too. That's always the worst question because--

Eric Kim: I always tell them, if you were my good-looking uncle, this is what we would do. So for those patients that go to radiation, is there anything you do or how do you decide who needs to get ADT and what the duration of ADT is? Is that a shared decision with your radiation oncologist? Are there any tools that you use to help parse that out?

Aaron Berger: Yeah, I mean, our protocol typically for any patients being referred to radiation or really even those patients with lower risk disease considering surveillance is we'll typically get a biomarker. We typically use the Decipher genomic classifier test more widely than others.

Obviously, there's some new technology out there, AI-based, things like that. That certainly may play a role in the future. But we've been using the Decipher test pretty regularly. And I really think it's been helping to inform those treatment decisions. So if we order it when we have that initial discussion with patients saying, yes, your biopsy was positive, this is-- kind of lay out the potential options.

I'm a believer that even if patients are leaning towards surgery, I think it's always good to have them discuss with radiation oncology to at least understand all the options. I don't want people to have buyer's remorse and have surgery and then say, oh, my friend had radiation, I wish I would have done that or vice versa.

I think if they say, no, I don't want surgery, I think it's always good to discuss all the options so they can make an informed decision. But we try to order the Decipher test at that time. So then by the time they see our radiation oncologist two or three weeks later, that information is there and ready for them to review with the patient, and we work closely to make sure we're on the same page with that information in terms of ADT, yes or no, duration of ADT.

And obviously, for them, there's some benefit to that to say, OK, do we need to potentially treat a wider field? Do we need to include lymph nodes if they're very high risk? Do we need to intensify further with additional medications? So all those things play a part. But that certainly is kind of our first step, as far as when we refer that patient to our radiation oncologist that that Decipher test is kind of waiting-- waiting for them to review when they get there.

Eric Kim: Yeah, I think that's really well said. It's nice to get that out of the way because it takes a week or two to cook, and it's probably going to take two or three weeks to see the radiation oncologist. And at least for the patient that shores up the timelines, that way, they're not seeing radiation, have an incomplete discussion. It muddies the waters, unfortunately, if you delay the ordering. So that's a nice workflow.

Do you guys-- again, in your practice or in your group, do you guys dispense the systemic therapy yourselves? That's something I'm not used to doing personally because we've always had a little bit of a political battle with the medical oncologists to not touch that space. I'm curious for you guys if you're dispensing yourselves, and therefore, you could maybe even act on the Decipher result yourself.

Aaron Berger: Yeah, absolutely. I think that's definitely an interesting dichotomy between independent practice and academic centers in general. I know a lot of academic centers like yourself, it sounds like where the ADT portion is really not even handled by urology.

So very different for us. We do in-office dispensing, and certainly, if they do need injection or prefer injection, we do that as well. But our current protocol for patients with unfavorable intermediate high-risk disease, very high-risk disease where if they are leaning toward radiation, they are very likely going to need some duration of ADT. Now that duration may be still up for debate, depending on some of those other-- some of those other results.

But so our current protocol would be to send a prescription in for the oral ADT, Orgovyx. We dispense that from our dispensary. And our patients can normally get first month, regardless of insurance coverage with start program they have.

And then we'll check benefits. For some patients, it may end up getting more expensive. But we really like that, number one, because there's no surge effect with the antagonist. So once they start that, we know their prostate's going to start shrinking. Their cancer is going to start shrinking.

So if they do-- when they do see the radiation oncologist, they want to proceed, they're then kind of ready to go after that first few weeks because they can move on, get their rectal spacing, if you're doing that. They can get their CT simulation, get their treatment plan going, and they're kind of ready to go.

And then we can have a discussion with our radiation oncologist to decide, OK, how long do they really need to be on this for? And that's something that, again, the biomarkers and other testing can help determine the length of treatment or if any additional treatment is needed. So it's very different, obviously, in place to place.

But it is something, the ADT is something we certainly handle ourselves. Pretty much anything short of chemotherapy, we try to handle ourselves in our practice. I know that's pretty common, a lot of big, independent groups, but definitely very different in the academic world where you partner with the oncologist to take over all the systemic therapy. So it's just a very-- gets the job done either way, and obviously, just takes one more person to be involved to discuss pros and cons of ADT and all that kind of stuff. But as long as the patient's getting their optimal treatment, it works either way.

Eric Kim: Yeah, again, the grass is always greener. So it's hard to-- you always wonder what the other world would be like. But yeah, definitely a benefit, in my mind, to having the patient-- and I don't want to say it negatively, but having the patient see one less provider, just to streamline the workflow.

I think these patients, like you've said, they're anxious to get started. It's one less barrier or perceived hurdle to just say, hey, we're going to start you today. And then you're going to be ready to go with the radiation oncologist once you see them.

Aaron Berger: And what we've also done recently is I think that with a lot of patients now with PET scans having what we would think would be non-metastatic disease ending up to have positive scan and a PSMA PET scan, we've actually told our providers, if you order that first month of Orgovyx, just tell them to hang on to it, but don't actually start it until they get their scan because even after a week or two, if you have small areas of metastasis, they could really shrink and may not be visible.

Now, you can certainly make the argument that those aren't clinically significant anyways if they shrunk that quickly. But I think certainly having proper staging up front as well, so ordering that Decipher test, getting that referral to radiation oncology, and ordering your staging imaging all at that first visit is really important. So by the time they see radiation oncology, they have all the information they need to come up with a plan.

Eric Kim: And like you said, with Orgovyx having such a quick onset, that's a really nice way to, again, streamline care for the patient, not to mention the quick offset in testosterone recovery for those short-term ADT patients.

Well, if we can, let's jump to a different topic. Let's cover post-prostatectomy biochemical recurrence. For you guys, do you have anybody that you're doing adjuvant for anymore? I know after RADICALS-RT and RAVES, yeah, adjuvant radiation kind of disappeared pretty abruptly.

But everyone talks about early salvage and early, early salvage. But do you guys do any true adjuvant anymore? Are there patients that that may be appropriate for?

Aaron Berger: Honestly, we really don't. That seems to be kind of the trend. I mean, as you just mentioned, there's multiple trials that show that early salvage is basically equivalent. And obviously, with anything, we don't want to overtreat patients. I think that's where we got into trouble 15 years ago with overtreatment of low-grade disease, which probably prompted some of the US task force discussion on PSA, which is where we're at now with a lot of people diagnosed with metastatic disease. That's a whole separate discussion, obviously.

But we don't want to overtreat patients. And there certainly will be some that you think may need radiation at some point, and they turn out to be fine. And again, that's another area where I think the biomarker testing and Decipher specifically in this post-RP space has been well-studied and really can inform that decision in terms of do they need-- do they need early salvage?

There's been some studies showing what those Decipher high-risk patients and getting them started at 0.2 or less, it can have some overall benefit, whereas patients with a lower Decipher score, maybe you can wait and do that more delayed salvage. So that really can help.

And then other trials have really looked at do they need to be intensified on the radiation side with adding pelvic nodes? And then, of course, the adding ADT or not to add ADT and that biochemical recurrent setting along with salvage radiation. So again, we don't want to overtreat patients. Lots of discussion of late as far as potential toxicities of ADT. Certainly, patients don't like the side effects of ADT.

So if you can use the tools we have available, like Decipher, and say, OK, this patient is a low Decipher score. We do think they need salvage radiation. But based on their low Decipher score, we're not going to give ADT. And they may actually do just as well. And in some cases, in the trials, they had poorer outcomes if they were given ADT for low Decipher scores. So we obviously don't want to hurt the patient, number one, let alone, overtreat.

So I think that really helps to inform the treatment decision and then, of course, have that discussion with your radiation oncology colleagues to-- and the patient, of course, and have that shared decision making in terms of what's best for them in their post-RP BCR space.

Eric Kim: Yeah, no, I think that's really well said. For me, we use a lot of ultra sensitive PSA. And if it starts to uptrend, that'll be our trigger to send a Decipher genomic classifier on the RP specimen. And again, you're right. I mean, time will tell. Time explains the biology better than any other marker that we have.

So it is a better world, I think, that we're in where we can monitor PSA closely and not pull the trigger so fast. And then yeah, it is remarkable seeing some of that data showing that for the low Decipher patient, if they get ADT in the salvage setting, we're actually killing them. I mean, we're actually harming the patient. Maybe that makes cancer specific survival look good but doesn't make us feel good and doesn't make us good doctors, which is really--

Aaron Berger: No, I mean, I think that data was probably surprising to a lot of people that there actually can be some worse overall survival. We don't think about ADT having-- I mean, we know about the side effects that it certainly has, as far as hot flashes and energy levels and the weight gain, all that kind of stuff. But you wouldn't think it would actually have a negative survival benefit, especially in a BCR setting.

But that's what the trial showed. So I think it is an interesting thing that some people may not really even be aware of. And the other factors, as far as we have our disposal certainly in germline genetic testing and other types of testing, which a lot of these higher risk patients who may have recurrence should be-- should be getting anyways, which is still probably underutilized overall. But if they do have a BRCA mutation or something like that, I mean, those are going to behave worse and probably need to be intensified. So I think it's important to use all the tools at our disposal to really optimize treatment for an individual patient. We talk about precision medicine. So I think we really need to use everything we can to make sure that patients are being treated properly but not overtreated.

Eric Kim: Yeah, I think hopefully, sooner than later, personalized medicine is here, but I think these are the steps to get there, right? Imaging in the right patient, biomarkers, and further testing in the right patient, and then deciding upon treatment based on additional data, not just sticking with PSA and Gleason score, which we've had for a long time.

Now, so again, I don't know if you've seen this. I know they were talking about it at AUA, but Decipher is now going to have a metastatic test. I think really just showing that that Decipher very high-risk patient, both in the high-risk space and in the BCR space, has a lot of shared biology to the metastatic patient, which makes sense. I don't know if you saw that. And maybe tell us, how are you plan on using it? I mean, is it for the newly diagnosed metastatic patient? How does that change your guys' workflows?

Aaron Berger: Yeah, I think that's a great question. I think it's really interesting advancement for the Decipher test. Basically, they're going to have a new test using a cutoff level of 0.85. We're all familiar, I'm sure they've used it where it's zero to one is the-- zero to 0.4 is low risk, 0.4 to 0.6 is that intermediate, and then 0.6 and above is high risk.

But in a few trials, 0.85 was that inflection point, especially in the very high-risk metastatic space where people did worse or develop more metastasis. So I think-- and statistically, if you look nationwide, even though we have multiple large trials showing that adding an ARPI to ADT for metastatic patients is the right choice or even triple therapy with chemo in some patients, it still is vastly underutilized. And ADT monotherapy is still used way more than it should be.

The most recent guidelines have now basically discouraged ADT monotherapy based on all those trials. But it's still done statistically, if you look at claims data, a lot. So I guess, for me, I think using that Decipher metastatic test may help decide which patients potentially need triple therapy up front. I think that's probably maybe what I'll use it the most.

I'm a strong believer that doublet therapy for pretty much all these mCSPC patients should be what's at least offered. Now, patients may refuse. They say, I don't want more pills. I'm worried about toxicity, whatever. But we certainly offer it to all our patients. But for those patients where you're maybe on the fence, do they need triple therapy or not if they don't have liver mets, lung mets, they're older, is chemotherapy really needed, that may be a great way to use this.

And then for those folks that for whatever reason just are not on board with giving an ARPI upfront, maybe this will be one more reason to say, hey, their Decipher metastatic test is 0.95. You're really doing them a disservice and you're impairing their survival by not offering them additional intensification of therapy.

So I think it's very-- it's the next step, the next evolution of how this Decipher test can be used, similar to how it's helping us determine for those high-end, very high-risk patients, do we need to intensify with abiraterone? There's been several studies looking at that.

So I think that's a similar way, we can-- it's really about intensifying or de-intensifying therapy for these mCSPC patients. So that'll be kind of on the horizon very soon. And it'll be one more tool we have to help really be precise and treat these patients appropriately.

Eric Kim: Yeah, absolutely. It's an exciting time for, I think, exactly that reason. There's more tools in the toolkit and then more tests to help rationally decide which tools to use, which--

Aaron Berger: Yeah, absolutely.

Eric Kim: Well, great. Well, thank you so much for taking the time this morning to talk, and hopefully, I'll see you at GU-ASCO or maybe next year's AUAs.

Aaron Berger: Sounds good. Thank you.