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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 gonna talk a bit more details about our main endpoints of this study this is a nice study it's an open access so if you if you guys are interested you just take a look over there you're 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 capro g the kappa preoperative capra in the post operative capro score i'm going to talk a little bit about this uh about the capra as well so that's the main the main uh goal that we have first starting with capra is a very known uh tool here validated to uh basically to estimate the risk of biochemical recurrence after radical prostatectomy and this is a nice uh uh tool if you guys don't use it i recommend it to start using it's very well known in all uh recent publications especially, and it associates some 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 PSa, 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 uh grade let's say over there the first square over there that you see from zero to two you have a five a year biochemical risk three to five and six to ten and also in the post-operative score and our main uh objective here is to show that now the importance now that 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 of the patient is very important as a prognosis as a progression so associating uh 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 uh um genomic assay that we have and this is basically what we see here right what we see in a patient the psa mri biopsy grade and clinical stage and etc what the gp talks a little bit about the tumor characteristics here, 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, androgen, cytolysis, cellular organization, stromal 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 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 to 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 gonna tell the chances of having a high grade disease which is a Gleason 4 higher than 4 plus 3 a non-organ confined disease you can see the percentage here 10-year metastasis and prostate cancer death in 10 years. We presented previously 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 reality using the the gps score our study here we got almost 1 000 patients 955 patients with a median follow-up of 16 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 quote. This is very important to say. This one of the limitations of the article that I'm going to talk a little 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, So, 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 1000 patients, that one capra point was pretty much equivalent of six gps points there when we did association between two and when we're talking about post operative scale one capra uh s point was pretty much the equivalent of 10 gps point this is how we calculated just talking a little bit about the methods and then you guys can take a look at the the paper if you want to go deeper on that so basically the capra score plus gps divided by six we're gonna have a final uh score over here and in the post-operative settings a copper score plus the gps divided by 10 you have another uh 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 uh it's showing it's pretty it's showing a performance of a predictive uh model okay so if you take a look at the first example here the capra alone is showing us 0.67 uh percent in the copper uh plus the gps when we associated the copper with the copper lift the gpx we could improve significantly over here from 0.67 to 0.76, so almost 10 points here. And a C-index of 0.7 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 is not uh uh that significant compared to the preoperative also it was statistically significant but it's only only added uh 0.003 from 0.81 to 0.84 but um also in the pose operative 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, okay? 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 to 8, those are the favorable ones. And the CAPRA plus the GPS, having a grade more than 9, those are unfavorable. So this is according to our findings. And these two graphs, you can see, you can take a look at the CAPRAS score and the CAPA after using the GPS. hazard ratio here 1.54 and the second one 1.31 you see the difference and also the statistic value of that um and also in this one when you see the capra post-operative capra with the post-opperative cap associated with the gps you see that has a ratio from 172 to 1.58 you see the differences in the curves here that's a very interesting i'll suggest you guys to go there and to 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 too but we could improve the prediction of those models those clinical models using the gps score in the way that i 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 four. If we put in a CAPRA square, it will be a CAPSA score four, But once we associated with the GPS, we had some differences there. 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, grade group, MRI here, positive course, and et cetera. When we put in the CAPRA model, both will have the same CAPRA score, but once we associate with the GPS, one patient had a GPS of 18, the other one a GPS for 52. and when you see the calculations, the second patient will have a worse prognosis. So this is showing that the clinical tools that we have, they're great, they are 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 gonna have a much better association when we have those two patients two young patients considering a focal therapy and etc and we have two patients with the similar age similar PSA grade group clinical staging once we put in a CAPRA score again they're gonna have similar CAPRA scores 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 a external validation also uh but this is something that we discussed in the article perhaps the guy that we think that our great candidate 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 underwent radical prostateectomy, we have all the patterns here, which is extracorporeal 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 the 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 et cetera. And limitations, it's important to talk a little bit about the limitation of the study. This is a single center study.This is our experience, as I said in the previous slides, is something that we did here. This was 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 replying 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 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 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 and now for the panelists and for discussions and further questions thank you very much but I before we start I just want to introduce both panelists here they're very well known but I just wanted to introduce Andrew Weiner he's chief of urology in NYH health plus Hospital Kings County and associate professor program and 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 graduate in Columbia University, Vagelos College of Physicians and Surgeons. And he has, he's a high volume surgeon in prostates in prostate cancer, BPH, and all those surgeries. So let's start a little bit. Let's start Andrew and Jamie. What do 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, 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, it 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. 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'RE 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 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 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 said 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 in your prelude here dan lynn uh neil patel published in 2025 this beautiful paper um 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 gg one and uh 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 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 that's a great that's a great point and i Think something that i tell all my fellows and the the students that those now the genomic profiles, the genomics 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 et cetera. 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 what the 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 pathologist yeah exactly so 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 uh 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 a problem. 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? Jamie, 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 the next year 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. Similarly, toward the end of the day, I saw another patient who was by all accounts favorable intermediate, low volume, three plus four, a couple of cores of three plus three, one of pattern four, I think it was 15, 20% pattern four 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 him up for surgery. 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 in 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 low volume favorable intermediate wrist disease less than two cores of gray group two with less than 15 to 20 percent of Pattern 4, exactly what you mentioned, Jamie. For these, I think that you have this tool in your toolbox that is covered by insurance and it's readily available. And 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. 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. And I think the 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 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 on the test is under $300. And while that's a different amount of money to every single patient, and 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 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. me, you know, 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, you Know, 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 reason to be concerned about any psa bumps i'm watching that patient so if i can save the healthcare system you know mri biopsi dollars we're actually saving money on in the long run no agree 100 and very similarly i mean that's still someone 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's a win for everyone involved yeah now i strongly i strongly agree we put them in the paper if you guys take a look we put this um financial discussion more because um here in the us 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 money 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 um one of the questions we have here is that is there any point that you guys don't use or if you comfortable what kind of patients you feel comfortable or not of not using it uh or you use for all your patients how do you usually uh apply that to your clinical practice how do you guys usually tackle uh this uh uh this part of the in your clinic andrew why don't you take this one first yeah i mean i i would say that if you have have gray group 1 and 5% of one core and very modest PSA, somewhere between 4 and 10, 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, 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 now, 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 say 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 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 they seen 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, Iglesias 6, and say, no, how come this Iglesial 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 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 uh clarify that scenario as well well. And, you know, I'm also increasingly in these, you know, grade 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 1, you know, probably 30, 40%, PSA of 7, 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 an 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 features, I think you could make the argument to deescalade that protocol. Yes, and this is what it was exactly what i was going to enter the opposite also is the as you just said the opposites also like you're doing the real protocol every two years a new biopsy you have a low profile low genomic uh profile over there you can wait a little bit more you can counsel the patients because the the the genomic component of the tumor most likely won't be aggressive that you're gonna need to do about every two or even three years and i want to plug dan lynn 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 upgrade and 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'd be an mri um i'm gonna throw exo out there you know whether that changes um and and see if any of those things um make us decide to do a biopsy in the future perfect and how you guys usually um counsel your patients for instance you have your patient in your clinic and then you're gonna order a gps test or any genomic uh test over there how do you guys counsel for doing the the test this is the first question the uh we have here and then after having the results how are you gonna say this by this patient well let's say it's a high gps over there score do you have a genetic counselor to talk to them or you do it uh by yourself or you do both uh i'll i'll wait for you guys and then i'll talk how we're doing in our center but uh uh 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 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 the with the genomics um i'm not necessarily getting them plugged in with those extra ancillary services um but more using that as one of those many multi-parametric factors in helping to 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 it, 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, you know 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, 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. And I like to explain to patients a lot of times, cancer is you outliving your mutations. And so every, you know, cancer's 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 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 prediction of metastasis not that you're gonna have the metastases but based on a court and a 30 I don't know 10% of those patients had metastasis so that's basically what you have now and also I strongly believe that usually the wives of the the patients they're more they have more questions and they're more concerned about those tests so I usually try to put both together and 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 and so i i think just sitting down and explaining what we need uh here um we have another question here if the patient elect 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 compared with the final pathology but what do you guys think the gps will change the surgery protocol or the way you're doing how do you guy tackle that so um there's actually i i love the study that you guys put together uh in your group marcio you know about the inc 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 model were grade group and the GPS score so in a multivariate model only GPS and grade group were significant for you know basically adverse pathology at the time of 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 prostatectomies 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. And i 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 higher GPS, MRI, what have you, I'm not going to be hugging the capsule quite as closely. I'm certainly not going be risking a capsular incision in the same way I might with somebody with a lower risk profile. Yeah, I totally agree, Andrew. 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 an 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 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 as you said as well. I don't change my approach there based on those values like, oh yeah, a GPS of 30 or 35, but I know that on that side, most likely I'm going to have something extra. I have a higher chance. So I go with more cautious. I won't change because I also like to do nerve sparing in all patients, unless you go in there and you see that it's very stuck, even in Gleason 9, it's all very stuck and then you go outside of the process and take the whole thing out but I won't I won' change that much based on the on the value like 29 30 35 etc but I'll be more cautious that's the only thing that I would do if these patients they have the bit that 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? Actors violence, 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 and we can see what what's happening there in your practice what is the biggest challenge to overcome patient understanding uh workflow reimbursement interpreting discordant results and other so wait like two minutes i'd say like this i think two minutes too much right people it's like two questions one minute per question is too much here okay we'll get you guys get you guys some responses uh 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 poll thing is so cool. 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 gg and then as gps comes back let's say it's 35 okay because if you take the extreme like 55 yeah 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'm not going to another MRI. I'm just going to go straight for, I'll probably get a PSA at three months. And then, you know, if that PSA is rising significantly, then maybe we'll pull the trigger. But if the PSA's reasonable, then I'll re-biopsy him at six months. No, I think that's 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, great group two. So that's their two points to keep them in low-risk CAPRA. So PSA less than six, 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 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 biopcy. But I don't necessarily think I'd recommend taking him to surgery at this point. Okay. So what about you, Marcio? Yeah. Oh, my opinion. Okay, first, I will put both decisions on the table, right? Usually those younger guys, let's say younger 62 to 65, they're not the candidates that want to operate, but depending. Some guys are very particular with that, with cancer and et cetera. I totally agree. I would do a biopsy within six months to one year, not more than that, not passing one year. But I would offer the treatment. I will 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'll 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 active surveillance, I will do a biopsy within six to one year, not more than that. Yeah, those are great perspectives. And in this one, we've only got a couple minutes left. So speed round of answers on this last one. In your practice, what's the biggest challenge to overcome? 33% said patient understanding, 33% set interpreting discordant results, which is great with the topic of this presentation today. Workflow at 11% and reimbursement at 22%. You know, what's your guys' take? What's the single biggest challenge to overcome in your practice? Lightning round. You dig it, Jamie. I'm going with discordant result. I think workflow and reimbursements 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 uh 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 that's important we still have an area there around the 20s that we have some sometimes even us with some questions there we intensify or not but to me I think patient understanding 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 a treatment there, but they get this information of the GG1, yeah, but Gleason Grade 1, I'm an active surveillance candidate, so sometimes they come with this information from Shatibiti, from something extra there, and we have the genomic thing that they don't 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 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. 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 conformatory. I do serial GPS because I find that the biology changes. Oh, you're on mute. Sorry about that. If they go from gray group one to gray group two i get it on both if they stick a gray 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 go for uh for a confirmatory okay wonderful well we are at time this evening i would like to extend my gratitude to our panelists. Dr. Moscovitz, thank you for moderating today. Dr Kearns and Dr. Weiner, thank 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 good night thank you good evening Take care.