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Hello and welcome. I am Denae Wells, the GPS Marketing Product Manager at MDX Health. As you guys all know, prostate cancer decisions are not one size fits all. Two men with the same risk score can face very different futures. And that's exactly what we're going to talk about in tonight's webinar. We'll explore how patients' tumor biology and their clinical risk assessment work together to help inform shared decision making for you and your patients. um to lead us through i'd like to introduce tonight's author and keynote speaker dr marcio muscovus he is a urologist a robotic surgeon and research coordinator at advent health global robotics institute he brings extensive expertise in telesurgery across multiple international platforms and he holds a phd in robotic surgery and has authored over 150 scientific publications earliest earlier this year in european urology oncology dr muscovis and his colleagues published integrating genomic prostate score with preoperative and postoperative cancer of the prostate risk assessment scores, or CAPRA, to predict biochemical recurrence after radical prostatectomy. This is the work at the heart of tonight's discussion. If you do have any questions during the presentation, please do submit them through the Q&A feature. They will be saved and answered during the panel discussion at the end. And to make things a little bit easier today, we did pre-record the publication overview, but when that concludes, Dr. Miskovis will formally introduce our other panel members tonight who will share their cross-institutional perspectives this evening. All right, without further ado, let's get started. So hello, everybody. I'm Dr. Marcia Moscovas. I am a urologist, uro-oncologist here in Celebration, Florida. And it's a great pleasure for the invitation. Thanks for inviting me. And I'm going to talk a little bit today of our recent work in European Neurology, our recent publication here, talking a little about the GPS, the association of the GPS with the CAPRA score, basically to predict biochemical recurrence. But I'm going to talk a bit more details about our main endpoints of this study. This is a nice study. It's an open axis. So if you guys are interested, you just take a look over there. I'm going to see this work a little bit deeper. And the main idea of the study was to associate the GPS score, the genetic score with the CAPRA and the CAPRG, the CAPA preoperative CAPRA, and the postoperative CAPRA score. I am going to talk a little about the CAPra as well. So that's the main goal that we have first starting with CAPRA. It's a very known tool here, validated tool, basically to estimate the risk of biochemical recurrence after reticuloprosetectomy. And this is a nice tool. If you guys don't use it, I recommend to start using it. It is very well known in all recent publications, especially. And it associates some scores, associates scores with the PSA, Gleason score, clinical T-stage, percentage of positive surgical margin, and age of the patient. This is the preoperative CAPRA and the CAPRA-S score, pretty much putting the PSAs, pathology, GLEASON score, surgical margin if it's positive or negative. And then overall, in both situations, we're going to have a grade for that. So grade, let's say over there, The first square over there that you see from 0 to 2, you have a 5-year biochemical risk, 3 to 5, and 6 to 10, and also in the postoperative score. And our main objective here is to show the importance now of the markers, the genetic markers, such as the GPS and the genetic tools that we have in prostate cancer. because only the clinical tools, they're good, but they still need some further improvements because now we know that the genetic value of the patient is very important as a prognosis, as a progression. So associating Kappa score or all these clinical tools with the genetic profile will be a better tool to stratify the best patients. Talking about the GPS a little bit, very well-known genomic assay that we have, and this is basically what we see here, right? What we see in a patient is a PSA, MRI, biopsy grade, and clinical stage, and et cetera. What the GPS does, it talks a little about the tumor characteristics, your tumor biology, aggressiveness, recurrence risk, and all the hidden genomic information. So it's a complementary tool that we're using, and it goes from 0 to 100. The core of the GPS basically works with 17 genes. We can see here prostate-specific genes and reference genes, androgens, signalized cellular organization, stroma response, cellular proliferation, and then at the end you have the GPS result, and this is how we're going to use. This is the typical report of the GPS. You're going to have the profile of the patient with the Gleason score, PSA, clinical stage, et cetera, prostate volume, and other parameters that we need to calculate the score. Once we have the score, we're going put the patient in low, moderate, or high likelihood. What is likelihood of what? Of adverse pathology at a radical prostatectomy. Okay, so after that, we're going to tell the chances of having a high-grade disease, which is a Gleason 4 higher than 4 plus 3, a non-Ordan-confined disease. You can see the percentage here, 10-year metastasis, and prostate cancer death in 10 years. We presented previously in our papers talking a little bit about the correlation of the GPS pathology. And after you have the GPS score, you can decide on active surveillance, definitive treatment, or informing the treatment intensity, etc. But now, not only the GPS, associating the GPS and the CAPRA score according to our paper, we could find a better tool to stratify. And this is exactly what we're doing. We're putting the CAPRA preoperative and postoperative score and showing a little bit of the molecular reality using the GPS score. Our study here, we got almost 1,000 patients, 955 patients with a median follow-up of 60 months. So we're a high-volume center here in celebration on prostate cancer and radical prostatectomy. we were doing around 1,200, now a little bit more, more cases. And we got a retrospective report. This is very important to say, this is one of the limitations of the article that I'm going to talk a littlebit later, but it's a retrospect of almost 1,000 patients that underwent a GPS with a nice follow-up, five years median follow-ups. And our primary outcome was biochemical recurrence, which is graded as a 0.2 in two consecutive measurements. And then it's a single surgeon with a dedicated uropathologist with a standardized approach. This is something that also it's an key point when you're evaluating such tests and such studies. Okay. So basically what we have, we had a beta coefficient here and we stratified this coefficients in preoperative and postoperative. And this is not something, this is not a measurement that came from our head. This is involving a very complex statistic method. So we found, according to our court, our experience of almost 1,000 patients, that one CAPRA point was pretty much equivalent of six GPS points there when we did the association between two. And when we're talking about post-operative scale, one CAPRAS point was pretty much the equivalent of 10 GPS points. This is how we calculated, just talking a little bit about the methods. And then you guys can take a look at the paper if you want to go deeper on that. So basically the Capra score plus GPS divided by six, we're going to have a final score over here. And in the post-operative settings, Capra Score plus the GPS divided by 10, you have another trend over there. Also, you guys can go to the paper. And what we found here is you can see the second bar over here, this is a C-index showing a performance of a predictive model, okay? So, if you take a look at the first example here, the CAPRA alone is showing us 0.67 percent, and the CAPNA plus the GPS, when we associated the CAPA with the GPS we could improve significantly over here from 0.67 to 0.76, so almost 10 points here. And a C-index of 0.66 means that the model will identify which patient will recur before another patient in about 76% of the time. So that's what we have. In the post-operative, it's not that significant compared to the pre-operatives. Also, it was statistically significant, but it's only added 0.003 from 0.81 to 0.84. But also in the postoperative we can say that we had an improvement here. So basically talking about these scores, a CAPRA preoperative plus a GPS of 26, we're going to have a score from 0 to 8 at the end. So those are the patients that are favorable according to the grading that we're doing in our study. So CAPRA score, the GPS divided by 6, if it's in the range from 0-8, those are favorable ones. and the CAPRA plus the GPS having a grade more than nine, those are the unfavorable, okay? So this is according to our findings. And these two graphs, you can see, you can take a look at the CAPRAScore and the Capra after using the GPS, the hazard ratio here, 1.54, and the second one, 1,31. you see the difference and also the statistic value of that and also in this one when you see that Capra post-operative Capra with the post operative cap associating with the GPS you see it has a ratio from 172 to 1.58 you see differences in the curves here that's a very interesting I'll suggest you guys to go there and take a look okay so the evolution of the prognosis here. We had a CAPRA, which is a great tool. CAPRA-S, also a great tool, but we could improve the prediction of those models, those clinical models using the GPS score in the way that I just showed, okay? So when we're talking about the clinical scenario here, those are real cases that I'm putting here. Those are real scenarios that I had. If you have the patient A here and the patient B, they're pretty similar, 62 versus 63, PSA very similar, great group, clinical staging. Okay, both are CAPRA score 4. If you put in a CAPRA score, it will be a CAPra score 4, but once we associated with the GPS, we had some differences there. We had one, we had a GPS of 15, the other one 65. And if you do the calculations, this patient here with the same caproscord are going to be in a worse prognosis compared to the first patient. The same happens with these two patients, almost pretty similar age, PSA, great group uh mri here uh positive course uh and etc when we put in the capra model both we have the same capra score but once we associate with the gps one patient had a gps of 18 the other one a gpso 52 and when you see the calculations the second patient will have a worse prognosis so this is showing that the clinical uh tools that we have they're great uh they're doing a much better job than the previous years that we didn't have them, but now associating with the GPS profile and all those genetic profiles, we're going to have a much better association. When we have those two patients, two young patients considering a focal therapy and et cetera, and we have two patients with a similar age, similar PSA, great group, clinical staging. Once we put in a CAPRA score, again, they're going to have similar CAPRA score. However, when we see the genomic profile, we're going to have one having a GPS of 22 and the other one in 34. So perhaps it's not established because this is only a suggestion that we give in the paper over there. This is not established, not even guidelines. You need external validation also. But this is something that we discussed in the article perhaps a guy that we think that are great candidates for the focal therapy they are not due to the genetic profiles they have better chances of having a more aggressive genetic profile over there when talking about after radical prostatectomy here two patients that under rent-righted copacitectomy, we have all the patterns here, which is extracurricular extension, margins, and et cetera, CAPRA postoperative, CAPRAS of three. And when we associate with the GPS score, we see that the second patient is a patient that we're going to need a closer look. We're going need to pay more attention at this patient. And also it's important to counsel telling that genetically he had a more aggressive cancer. So we need to have this closer follow-up with the patient. So the main question I already answered during the slides is why adding the genomics in there, right? The clinical dilemma. So I showed a lot of different cases, okay, that are associating the genomic with the CAPRA score. We're going to have a different plan on this patient, a different stratification and a different counseling, or even a different strategy of this patient when talking about the focal or surgery and etc. And limitations, it's important to talk a little bit about the limitation of the study. This is a single center study. Our experience, as I said in the previous slides, is something that we did here. This This is a retrospective study with 1,000 patients, single-surgeon center. It's very, very important to do external validation. So if you guys are planning to do some further studies, we're glad to collaborate as well. But I think it's important to have more literature talking about external validation and doing the replication of this study in other centers. We know now the path forward that the genetics, associating everything in genetics, will be the way to go. Not only prostate cancer, but bladders, kidneys, and other types of cancer. And we should always say that one size doesn't fit all. I showed a lot of different examples over there of patients that look like similar, but the genetic profile of the patient can tell us something more than most likely going to benefit during the treatment, during the follow-up, and during the plans for these patients. And thank you very much for the opportunity. I'm going to open now for the panelists and for discussions and further questions. Thank you very Much. But before we start, I just want to introduce both panelists here. They are very well known, but I just want to introduce Andrew Weiner. He's Chief of Urology and NYH Health, plus Hospital Kings County and Associate Professor, Programming Director of Urology Residency, Clinical Advisory Dean for Medical Students in NCUNI, Downstate and Director of Robotic Surgery in Kings County. And James Kearns, Jamie, is a board-certified urology graduating Columbia University, Vagelos College of Physicians and Surgeons, and he's a high-volume surgeon in prostates and prostate cancer, BPH, and all those surgeries. So let's start a little bit. Let's start, Andrew and Jamie. what you guys have to discuss here, if you guys have anything to share about your practice and what you saw in the slides. I have a few questions already, but I just want to open for you guys to introduce a little bit to us as well. First of all, congratulations. I think this is a really nice manuscript paper showing what a lot of us are seeing in our day-to-day clinical practice. We have so many patients with very similar favorable intermediate type of risk profiles. I think that's the gray zone in prostate cancer decision-making these days. And to really rigorously take a look at your data and see how genomic analyses can impact and really give us more data to sink our teeth in with our patients is really exciting to see. And it really falls in line with a lot of what we're seeing in our clinical practice and is encouraging going forward. andrew yeah i mean i couldn't agree more i think that to put some data to you know what we're seeing clinically is is really valuable um you know i love using genomic biomarkers and i get you know some feedback that not everybody does and you know the reality is what we are facing these days is like a puzzle and we're trying to put together the pieces and figure out what's ultimately best for patients. And we know that age and PSA and gray group and T-stage, MRI, they're all very, very important variables that we take into consideration, but they're puzzle pieces. And they don't tell us anything about the behavior or the biology of that patient's disease. And you guys showed this really nicely that you can take these clinical factors, but that the biology actually adds significant value. And so for me, these genomic class classifiers like GPS, they don't replace the clinical pathologic variables, but they help us unmask, I think, potentially aggressive biology. And so, you know, if I were to say where I find the greatest need or value in these tests, it's really to be able to transform this uncertain moment where you're sitting together with a patient and their family And you say, well, I'm pretty sure it's this because my pathologist called it that. But you can actually personalize a discussion of risk for that individual and ultimately allow them to make an educated decision based on how they want to proceed. Yeah, I totally agree. And I think now with those genomic profiles, we're having some questions that we used to have like 10 years ago when you see like two patients in clinic, you say this patient went so good in the post-op and the follow-up and the PSA recurrence and this patient was so bad and they were so similar. I think now the genomic profiles, they're giving us more tools and understanding why this is happening. I think that's a great point here. I just want to make one more comment about that. So to your point, Marcio, not every GG1 is the same. And you mentioned this in your prelude here. Dan Lin, Neil Patel published in 2025, this beautiful paper, JAMA, I think, that showed that you can actually stratify GG1 alone into low intermediate, unfavorable intermediate, and high risk disease. And we're all seeing this. Jamie, I know you're seeing this, you can see explosive GG1. And, you know, what I want to know is what's happening under the hood. And that's where these tests really shine. exactly i couldn't agree more and you know that the gg1 is interesting i mean it's so almost dogmatic at this point that people want to say it's gg one do we even call it cancer yeah ignore it go away um and and i think that for most patients sure we we should be watching it and keeping an eye but you think of these guys with the strong family histories the high volume disease the PSA that's out of concordance. And you're like, look, I just need to continue to convince you that this is real. And I think that this helps with that overall picture. I mean, it's like a Polaroid picture. How much more can you add in to clarify what's coming in and bring it into focus? Yeah. And that's a great point. And I think something that I tell all of my fellows and the students that those, now the genomic profiles the genomic testing they made the scientific community think a little bit better about the gg1 because we had a trend five six years ago in some conferences no this is not even cancer guys don't worry about it and etc and we as a high volume centers we were seeing several of those patients having recurrence having problems having metastasis and nobody could explain why right and that's with that's with a trained geopathologist you know I've heard people say oh it's not it's because you don't have a trained geopathology you have an excellent yeah exactly so it's not that it's the biology of the disease that's discordant yeah and I think this is the first take home message that we have here you know never underestimate the tumors you have the profiles you have unless you have all those genomic identities to tell us a little bit more Of course, the vast majority, the GG1s, they won't give us problems. But some of them, when they do, we've seen some patients with some bad diseases after. And for both of you, just a few questions that we have here from the audience. And in our practice, where do we find the greatest incremental value for GPS beyond the traditional clinical value? So, guys, basically, where Do you guys use or who are the patients that you look and say, this is the guy that I need a GPS or this is something that we need to look a little bit further or you do for everybody? How do you guys do in your practice? Jeremy, you want to take it? Yeah, sure. I mean, honestly, I can think of two from today, just in clinic, my clinic this morning, it's my favorite thing of the week, right? But, you know, I had one guy this morning who was grade group one, PSA of 19.5, big prostate, it was, you Know, 90, 100 grams. And, but low volume grade group 1, T1C, we do a lot of prostate health index here is our secondary serum biomarker. And that was also favorable. It was in the lower risk, like 43, which for PHI is pretty low. And, you know, we see these patients a couple, I see these patients a few times a year where we see this really high PSA values. It's uncomfortable to watch him. His GPS is 13. And it was a really interesting conversation because I said, look, I don't like your PSA, but everything else here looks really good. Your GPS is excellent. I was actually referencing your data in the office. I brought up some of the prompt data as well. I think not for tonight, but I think that's also compelling in this conversation and was basically like, look, I don't like your PSA, but everything else is telling me this is low risk. And we made the decision that we're going to keep an eye on it. We're going do another biopsy in six months. And biologically, based on everything we can see, this tumor is very unlikely to do anything really aggressive. Um, similarly toward the end of the day, I saw another patient who was by all accounts, favorable intermediate, um, low volume, three plus four, a couple of cores of three plus three, one of a pattern four, I think it was 15, 20% pattern for distribution, but his GPS came back at, I Think it was 38. And so again, you add that picture in and you can say, well, this really influences the picture and we're setting them up for surgery. Um. And I think without the GPS, this is somebody who probably would have ended up watching his cancer. We would have done some biopsies in the future, but this is less comfortable to watch it. And given those advances in information, the tumor biology, seeing what you're showing right here with this information that plays very much into, he's probably more unfavorable intermediate and benefits from treatment. I mean, Andrew, it's funny because I, I have the same exact patients And from within the last two to three weeks, you know, I would say the sweet spot, if you were to ask me for this test, is high volume, you know, more than four cores of GG1, or low volume favorable intermediate wrist disease, less than two cores of grade group two, with less than 15 to 20% of pattern four, exactly what you mentioned, Jamie. me. For these, I think that you, you know, you have this tool in your toolbox that is covered by insurance, and it's readily available. And, you Know, for me, I can't understand why you wouldn't add that to be able to have the conversation with the patient to allow them to ultimately decide. You know, people ask me all the time, what's your cutoff for intervening? and you mentioned a gps of 38 well i use you know 30 as my cutoff for reassuring versus non-reassuring and i don't say treatment versus not treatment because it's a conversation this whole thing is a conversation about their disease and risk and what they're able to tolerate and then ultimately they decide and i think that that's where this test really shines is the higher volume grade group one and the low volume grade grade twos great guys yeah i have the same I have the same sensation in all of you guys. And the more we use, the more we understand about it, and the more we see the benefits, right? And as you said, Andrew, as soon as it's covered now by insurance and everything, I mean, this is something that I strongly believe that there's no way of coming back, right, to our previous practice without the genomic profiles. to improve fast. And I think to dovetail a little bit into that coverage and economic standpoint, I mean, I know you guys talked about the cost in the paper. In our current world of patient-centered medicine, and I think it's really important that we're looking at the patients at the center of this, the out-of-pocket is nowhere near the published price. And, I think we need to keep that in mind as well. Most patients are paying quite a bit less, even when they don't have full insurance coverage, but the ceiling on the test is under $300. And while that's a different amount of money to every single patient, I would never presume to say that that's insignificant or significant to any given patient. I do think we need to keep that in mind of, you know, when we're talking about healthcare costs, yes, there's the abstract, what does this cost the system? But very concretely, we know that we're not costing our patient an inordinate amount of money out of pocket with these tests as well. And that I think plays into it significantly too. And Jamie, for me, when you talk about healthcare costs to the system, you can actually make a very significant argument. And they actually have a few papers within the company and published in the medical literature showing that these tests save money in the long run. Because I use my GPS results to help tailor my active surveillance strategy. So if you have a low risk patient and a very low GPS, I'm holding off on restaging biopsy for indefinitely, actually. If there's no MRI lesion and there's not reason to be concerned about any PSA bumps, I am watching that patient. So if I can save the healthcare system, you know, MRI, biopzy dollars, we're actually saving money in the long run. I agree 100% and very similarly. I mean, that's still somewhat of an unanswered question, but if that negative predictive value is so high and we can save patients the cost and the inconvenience and the risk, that is a win for everyone involved. Yeah. No, I strongly agree. We put in the paper, if you guys take a look, we put this financial discussion more because um here in the u.s we have a different reality right we get we have like covered and everything some places they don't have too much access but um as you said it's already well established in the literature with some papers telling that how much we can save uh money uh using those tests to avoid further treatments further tests further exams so we definitely have advantages over there And I know that you guys are using a lot, but one of the questions we have here is that is there any point that you guys don't use or you feel comfortable, what kind of patients you feel uncomfortable of not using it or you use for all your patients? How do you usually apply that to your clinical practice? How do your guys usually tackle this part in your clinic? Andrew why don't you take this one first yeah I mean I would say that if you have grade group one and five percent of one core and a very modest PSA somewhere between four and ten I don't think you necessarily need a genomic classifier to tell you that that's low risk and so that's a patient that you could very comfortably say you know we're just going to repeat the PSA and go down our active surveillance protocol. But, you know, for multiple cores for me, you Know, again, I think that this is equally if not more important than the MRI. I think the MRI helps target our biopsy. But I can't tell you how many PI-RADS fours have come back as grade group one. And I'm left scratching my head wondering, you is this real? Is this not? And it's the biological piece, the genomic component that really can answer that question. So I would say that aside from a very, very low risk, again, tiny little core, that's probably going to be insufficient for analysis. I'm going to get a GPS. Yeah, I totally agree on those really low risk patients. And I would see on the converse side, If somebody has a set of clinical factors between higher grade group, higher PSA, higher disease volume, that I'm going to recommend treatment one way or another, I don't know that I'd need to get a GPS in those patients as well. I mean, somebody's got a Gleason 8, 9, 10 prostate cancer, we're going to treat it. And so adding that additional test at this point in the treatment probably is not going to be a significant add for those patients either. So it's either a low risk or really high risk. I agree. And I'll put a scenario here. I didn't put in my lecture, but this is something that happens to us. And it's very usual, to be honest, very common to us, we receive patients from all over the state and even some other countries here in our center. And the biopsies done outside, they're not as accurate as the ones done in our Center, Of course, because you guys also as a high volume centers and high volume surgeons, you know that that your pathologist, you basically trust what they he or she is doing because of so many biopsies that they see. But in the community is not like this. So we sometimes change a lot our plans when we receive these patients with a biopsy. And for instance, you get a GPS that is sky high. A guy has one core of those biopsies that are like six cores, those not standard biopsys. So one core, a Gleason 6. And you say, no, how come this is a GLEASON 6? This genetic profile here is kind of sky high. So in some of these cases, those are key or red lights to us to do a new biopsy based on the genetic profile. I don't know how you guys deal with that. I believe you guys also have similar situations. but this is something that happens with us kind of usually yeah for sure that can happen and and um i think it also saves the patient another biopsy right you can run this test and it's going to take the index lesion which you're concerned about and and run and run an analysis but you know to jamie's point i think if i have a grade group three patient who's a you know few comorbidities i'm going to take him to surgery i don't necessarily need you know additional testing on that. But, you know, if I'm up in the air about treatment versus active surveillance or even intensification or de-intensification of ADT for my unfavorable and high risk patients who are going to undergo radiation, I'll run a genomic biomarker. So GPS can help clarify that scenario as well. And, you Know, I'm also increasingly in these, you know, great group one patients really tailoring my active surveillance strategies, not just avoiding the biopsy completely, but you know, let's take the patient with three quarters of grade group one, you know probably 30-40%, PSA of seven, they're in their 50s. By our institutional active surveillance protocol, once they get through their first two biopsies, we're doing them every two years across the board. But when you add in the GPS, if that patient's got a GPS in the 20s or maybe even low 30s, I'm not going to wait two years. I'm going to be doing that sooner in those patients. And whether they came from outside or inside, that's another place where it really tailors the protocol short of necessarily taking them to treatment, but can still have a significant impact on their care. Oh, yeah, absolutely. Could not agree more. I would even urge you to go so far as to push your institutional protocol on the opposite end, which is that to de-escalate some of this surveillance based on the genomic profile you know i put so much stock in this that i think in combination with path with genomics and all the other clinical feature clinical features i think you could make the argument to de- escalate that protocol yes and this is what it was exactly what i was going to and to the opposite also is the as you just said the opposite is also like you're doing the real protocol every two years a new biopsy You have a low profile, low genomic profile over there. You can wait a little bit more. You can counsel the patients because the genomic component of the tumor most likely won't be aggressive that you're going to need to do a biopsy every two or even three years. And I want to plug Dan Lin here because we invoked him. Dan Lin was my fellowship director and one of my key mentors in fellowship. And one of the things we published was the implication of negative biopsies on active surveillance and how, if you don't see cancer on a subsequent biopsy, that your likelihood of upgraded need for treatment down the road is exceptionally low. I would extrapolate that to say, if your tumor biology is demonstrated through one of these genomic tests is incredibly low as well, then perhaps those patients also don't need additional biopsies until we have some other signal, whether it be, you know, a serum biomarker, whether it be an MRI, I'm going to throw exo out there, you know, whether that changes and see if any of those things make us decide to do a biopsy in the future. Perfect. And how you guys usually counsel your patients, for instance, you have your patient in your clinic and then you're going to order a GPS test or any genomic test over there. How do you guys counsel for doing the test? This is the first question that we have here. And then after having the results, how are you going to say this by the spatial? Well, let's say it's a high GPS over there, a score. Do you have a genetic counselor to talk to them or you do it by yourself or you do both? I'll wait for you guys and then I'll talk how we're doing in our center. but there's some curiosity that people put over here. Yeah. I mean, I do think of genomics and genetics very separately for our patients. I mean, the number of patients with the, you know, RPMs, the rare pathogenic mutations are going to be pretty uncommon, especially in the low risk and even intermediate risk patient population. And for those patients, we have a robust genetics program. We get them intergenetic counselors. We'll look at polygenic risk scores and things along those lines. But I think with the genomics, I'm not necessarily getting them plugged in with those extra ancillary services, but more using that as one of those many multi-parametric factors in helping to talk about their specific cancers. Yeah, I agree with that. I mean, our genetic counselor is in such high demand from all of the different services that, you know, first of all, I think it would overwhelm them. And second of all, I don't think that that's their realm, to be honest. I think that these genomic classifiers help us make decisions as urologic oncologists or urologists, because, you know, all of us are taking care of prostate cancer. I actually would say that the low and favorable intermediate risk space is one of the hardest conversations and negotiations that we have in urology. If you have high risk disease, well, it's a hard conversation because they have aggressive disease, but we know what the treatment strategy is going to be. For this one, the number of options that are out there are plenty, and there's a ton of decisional regret and psychological burden that takes place with all this testing, plus the diagnosis of cancer. So I think we're stuck in this situation where we have to really understand what we're dealing with before we make our recommendation. And that's where this really comes into play. And the way I explain it to them is, you know, that exactly as Marcio in the video that you put forth, how I explain is basically two men can have cancers that look identical under the microscope. But, you Know, one tumor is biologically quiet, and the other one can be more aggressive. So in other words, you Now, genomic tests tell us how a cancer behaves. And, you know, genetic testing is more the inherited risk. And I think that's somewhat of a misconception for a number of my patients, at least. Yeah. AndI like to explain to patients a lot of times, cancer is you outliving your mutations. And so every, you knocancer is obviously a disease of somatic mutations for us when we're talking with patients. But I tell patients, it's outlaving your mutations and different mutations that have different levels of aggressiveness can look the same under the microscope. And this helps us get at the underlying biology and the underlying set of mutations and how those might influence the risk independent of what we're seeing under the microscope. Perfect. I agree again with you guys, but I'm very particular in talking to the patients about it Because my experience, I see the patients, they're very excited and with a big anxiety also when they have those tests and telling, oh, yeah, my GPS was 39. And they don't know basically what is that. So I think it's very important to us to sit down together. I usually try to print the whole thing and show them. So this is the prediction. That's what I told in the video. This is the predicton of metastasis. It's not that you're going to have the metastasis, but based on a court and a study, I don't know, 10% of those patients had metastases. So that's basically what you have now. And also, I strongly believe that usually the wives of the patients, they have more questions and they're more concerned about those tests. So I usually try to put both together. So the take-home message here is to explain well, sit down, because this can produce a high level of anxiety in the patients. We have patients that are calling all the time. Yeah, I have my GPS ready, but nobody's telling me what, you know what I mean? And so I think just sitting down and explaining what we need here. We have another question here. if the patient lacks surgery does gps change the surgery protocol um i'm gonna have my answers here but i'll i'll wait for you guys because what i will tell this is based on on a previous paper that we we did with gps comparing the final pathology but what do you guys think the gps will change the surgical protocol or the way you're doing how do you guy's tackle that so um there's actually i love the study that you guys put together uh in your group marcio you know about the you know every quartile uh that you increase it increases your risk of extra prosthetic extension seminal vesicle invasion and positive surgical margins um and i quote it all the time um but i would say that still for me the gold standard for surgical planning is the mri and so that's really helpful the two in conjunction but i will say there was a study at a ucla that looked at multiple variables including mri grade group psa and the gps score and the only one that stayed in the only two that stayed In the model were grade group and the GPS score so in a multivariate model only gps and grade group were significant for um, you know, basically adverse pathology at the time of prostatectomy. So for me, you know, the MRI is important. There's been many studies that show that for surgical planning, it's important. Um, and GPS is, is one of those factors that will also help me decide, but I wouldn't say I'm going to, you Know, nurse bear on a side or not side based on the GPS score. Uh, I'm actually being a little more provocative here. Um. I think virtually every patient you take for robotic prostatectomy is a candidate for nerve sparing until they're not. And so I can see a patient that I'm concerned about seminal vesicle invasion. I'm concerned about broad prostatic abutment of the capsule, what have you. And I absolutely am taking that into account. AndI think GPS is in line with those clinical factors of saying, hey, these are more aggressive diseases. And if I have any issues, stickiness, what have you in the OR, I'm going to bias toward getting outside a lot quicker. But I think that I give most of my patients the benefit of the doubt in terms of if those planes are coming off the prostate nicely, I think you can take them. And I think he can very reasonably be comfortable with that. But, you know higher gps um mri what have you i'm not going to be hugging the capsule quite as closely i'm certainly not goingto be risking a capsular incision in the same way i might um with somebody with a lower risk uh profile yeah i i i totally agree andrew uh our in our center and my practice as well. All patients undergo MRIs to do their prostatectomy. I think that's the best exam to do anatomy study and everything. And I don't, in some, we did this study with 720 something patients and we divided by a quart and then basically we kind of discovered that the GPS more than 29, the patient had a higher chances of extra prostatic extension as well but i as you said as well i don't change my approach there based on those values like oh yeah gps of 30 or 35 but i know that on that side most likely i'm gonna have something as extra i have a higher chance so i go with more cautious i won't change because i also like to do nerve sparing all in all patients unless you go in there and you see that it's very stuck. Even Gleason 9 is all very stuck, and then you go outside of the prostate and take the whole thing out. But I won't change that much based on the value, like 29, 30, 35, et cetera. But I'll be more cautious. That's the only thing that I would do if these patients, they have the GPS doing. Okay, we have a poll here. GPS plus Capra poll. 65-year-old patient, capital low risk, GPS returns higher than expected genomic risk. What is your management inclination? Active surveillance, definitive therapy, treatment intensification, and other. Okay, let's go on this one. We will wait a little bit, and then I'm going to read the second one, and then we can see what's happening there. In your practice, what is the biggest challenge to overcome? Patient understanding, workflow, reimbursement, interpreting discordant results, and other. So wait like two minutes, I'd say like this. I think two minutes is too much, right? People, it's like two questions. One minute per question is too many. Too much here, okay? We'll get you guys some responses. All right, let's see responses. All right. So it looks like on that first question, 65-year-old patient, about a third of the respondents chose definitive therapy. 22% chose treatment intensification and 44% chose other. Let's talk. What would you guys do in that situation? 65 years old, low-risk CAPRA, higher than expected genomics. i'm so excited right now i love this this whole pole thing is so cool um and and this is like this is real life patient i mean i can't tell you how many of these i see so you know i'm envisioning a 65 year old relatively healthy person who's got uh you know five cores of grade group one, and then his GPS comes back, let's say it's 35. Okay, because if you take the extreme, like 55, that's no question they're going for definitive therapy. But I would make the argument that 65, even with a GPS of 32 to 35, I think that patient is still an active surveillance candidate. But i'm going to tailor my active surveillance strategy and bump up that restaging biopsy much sooner. So I'm going to do it at six months rather than at one year or 18 months. So I am not going to another MRI. I am just going to go straight for, I will probably get a PSA at three months. And then, you know, if that PSA is rising significantly, then maybe we will pull the trigger. But if the PSA ist reasonable, then I will re-biopsy him at six month. No, I think that is great. I had a slightly different but still low-risk patient in my head. So I was going to go with a 62-year-old, so early 60s, Graker 2. So that's their two points to keep them in low-risk CAPRA. So PSA less than 6, T1C patient, low volume, whose GPS comes back at, say, 35, which would definitely kick them up in the CAPRA score. And I agree with you completely. I would not necessarily push that patient for surgery at this point, but I would do our next biopsy at six months, or let's say this is on the, um, confirmatory biopzy. And I would normally wait a couple of years. This is a patient in whom I'd bring back in a year rather than two years to do a repeat biopsych. But I don't necessarily think I'd recommend taking to surgery at this point okay so but what about you marcio yeah oh my opinion okay first i will put i will post decisions on the table right usually those younger guys let's say younger 62 to 65 they're not the the candidates that want to operate but depending some guys are very particular with that with cancer and etc i totally agree i will do a biopsy with him six months to one year, not more than that, not passing one year. But I would offer the treatment. I would tell him, look, this is what we have, your profile, your genetic profile is not as good as your CAPRA score or your GG1 there, but you have a chance over there to have a surgery, and then I will share the decision according to what they want to do. but definitely if I will keep them in an active surrounding cell we'll do a biopsy within six to one year not more than that yeah those are great perspectives um and then this one we've only got a cold minutes left so speed speed round of answers on this last one um in your practice what's the biggest challenge to overcome uh 33 said patient understanding 33 said interpreting discordant results which is great with the topic of this presentation today um workflow at 11 percent and reimbursement at 22 percent. You know, what's your guys' take? What's the single biggest challenge to overcome in your practice? Lightning round. You can take it, Jamie. I'm going with discordant results. I think workflow and reimbursements we figured out really well in our practice. And, you know, patient understanding, that's why we set up these long appointments to sit down face to face with patients and their wives. I say married men live longer all the time for a reason. And that's on us to really talk to those patients. But I think the interpreting discordant results is probably the biggest challenge I face. I think that interpreting discord results is challenging, but it's actually the equivocal results for me. So the ones, so I would put other in that category. It would click other on this poll. The ones that live at 28, you know, a GPS of 28 and have high volume grade group one or low volume grade two, 28, 29, 30, like hover right in that median of the bell curve. That can be a little bit confusing to discuss with patients and kind of prohibits me from making a strong recommendation. Yeah. Yeah, I think that's important. We still have an area there around the 20s that we have some sometimes even us we some questions there we intensify or not but to me i think um patient understanding um in terms of doing the treatment or not some of the patients there they go straight with the guidelines telling for instance gg1 with a high gps there you're telling them look it would be better if you operate if you do any uh if you do a treatment there but they get this information of the gg1 yeah but it really isn't grade one am i i'm i'm active surveillance candidate so sometimes they come with this information from shot to bt from something extra there and we have the genomic thing that they don't they don' understand yet so we kind of need to discuss okay we understand however now you have a complementary data from your genomic profile that perhaps you're not a good candidate over there there's not too many studies outside. So that, that conversation to me, sometimes it can take a little bit more time there. Great perspectives, everybody. Thank you. Okay. We have one question that came in from the chat. It's we'll do it as a quick yes or no answer. I'm sure we could get into a great discussion as well on this, but final one, and then we'll close for the evening. Are you guys getting GPS on the original path and confirmatory biopsy or just the original Pathology? We can do a yes or no on this one original and confirmatory or just original original and confirmatory i do serial gps because i find that the biology changes oh dr you're on you're unmute sorry about that if they go from grade group one to grade group two i get it on both if they stick at grade group when i use the original path alone yeah yeah that's also my my i would go with jamie also if we have a changing over there something different than the first one i would i would do that i would go for a for a confirmatory okay wonderful well we are at time this evening i would like to extend my gratitude to our panelists dr muscovist thank you for moderating today dr kearns and dr weiner thank you for participating. Absolutely enjoyed the discussion this evening. I think you offered some really great and unique perspectives, and I love that you all apply everything slightly different. It's great to see the differences. I'd also like to thank our audience for joining us this evening, if you have any questions, please feel free to reach out to marketing at mdxhealth.com. Otherwise, I hope everyone has a fantastic rest of your week, and have a great night thank you very much thank you jamie thank you andrew see you guys on the next one thank you everybody have a great night thank your evening take care