Chandler Park, MD: Great to be here back on Target Oncology. We have Treating Together podcast here and, we have some great friends, Ben and Manoj, can you tell us a little bit about yourself and your practice and what you do? Benjamin Garmezy, MD: So, I'm a GU medical oncologist in Nashville, Tennessee, here at a practice called SCRI Oncology Partners, kind of right in the heart of, near downtown. And I'm a GU investigator, and I also do a bunch of clinical trials, and I'm heavily involved in helping run the research program for Sarah Cannon Research Institute's national network Manoj Bupathi, MD: IÕm Manoj Bupathi. Chandler, thank you so much for having me on this podcast with you. I am a medical oncologist in Denver, Colorado, at Rocky Mountain Cancer Center. And I also work with Ben very closely at SCRI, and we co-lead the GU research program, from phase 1 to phase 3 research studies. Park: You know, I think one of the things that we think about is 85% of cancer patients are treated in the community setting. And so in terms of clinical trials, we want to be there for the community oncologists. And I feel like if you listen to the Oncology Decoded podcast, it's specifically for GU cancer. And some of the challenges that that that we all go through as not just as clinicians, but researchers and also to help our patients. So, we're going to be talking about real world challenges and practical applications of clinical data and clinical research. So, my name is Dr Chandler Park. I'm here in Louisville, Kentucky, co-director of clinical trials. And we do a lot of bladder, prostate, and kidney research. So, I want to kind of start off with the first question, importance of emerging clinical data and research in oncology. You know, the novel biomarkers, immunotherapy, targeted therapies, and AI in pathology, the gap between clinical trial findings and real-world clinical practice. There are challenges in staying updated with rapidly evolving data. So, what are some of the things that you guys do? Because I know you guys do a great job on your podcast to kind of share with everybody. What are some of the things that you two do to keep up with all the information? Garmezy: Yeah, I think, I think that's a great question and an impossible question to answer because it is complex. And even for some of us who have specialties, specialties within the community, it's hard, right? Not to mention all the doctors that we actually support with the research mission at SCRI who are seeing maybe 5, 10 GU patients a year. Half the time they're seeing blood clots. They're the real heroes. They have to know everything, right? So, we just have a small focus there right now and hopefully eventually can expand our educational missions. But, you know, specifically thinking about all this new technology that's coming in, we'll just start with that little chunk first. I think the biggest one and the most apparent one is the ctDNA story within GU cancers. Obviously, that story is evolving very quickly in urothelial or bladder cancer, maybe a little bit behind in in kidney and prostate and testicular cancers. But those tumor types themselves are starting to generate data with circulating tumor DNA. And I think what we're going to see is right now, ctDNA is kind of icing on the cake in urothelial carcinoma, as in, you know, you're treating your patients based on pathologic features and other risk factors based on NCCN guidelines. But now I think we're going to start to see not just prognostic implications but predictive implications of ctDNA. I know Dr Bupathi, I mean, I'm sure you want to jump in here because you're kind of our ctDNA expert as well. Um, but I think that's the biggest challenge. And it's trying to educate providers about how to use that specific modality. And then AI is coming around the corner. Bupathi: Yeah. You know, you bring up a very valid point, which is how do we keep up with the data. So, you know, for us, I think we're fortunate enough where we can dedicate some time to go to some of these big conferences and understand the cutting edge things. And we're also scientific in the sense that we are very much focused in academics. And we try to lead the research as well. And I think where our podcast and where Ben and I kind of excel a little bit more is how do we take that data that's being presented at the podium and say, this is what we see? Well, I think using that to what we're practically doing in clinic, combining those two things and giving me some of these pearls to our colleagues that are, as Ben said, the real heroes. I think that helps them guide their therapy modalities as well as surveillance for recurrence or progression, change of therapies, management of toxicities and such like that. And, you know, again, we're also in a fortunate place where we can network with a lot of other people and we can understand the pearls that, you know, you have as well as, you know, some of the bigger institutions like the MD Andersons or the Dana-Farbers or anywhere else. And we can understand how are they actually doing it at the academic, true academic settings where everybody's under one place vs where we're all staggered. I mean, that's one of our biggest challenges. We coordinate care in silos, right? But at the end of the day, we're the true quarterbacks trying to figure out where do we actually go and how much do we need to do. And we have a lot more nuances that we have to deal with. Park: Outstanding points. I couldn't agree more. And I think one of the things that makes our three practices unique is, you know, on the one hand, we get a lot of second opinions from community oncologists. And I feel like they kind of relate to us better because when they see the patients, they realize that, you know, we have some of the same challenges that they do. Right? And so then the question is the difference between the patient population and clinical trials that, you know, that that we have as community oncologists, research leaders vs those in community settings where we also give second opinions and we kind of reach out to the community practice doctors and say, we might not have a trial here, but we maintain that relationship and give second opinions. So, what do you guys typically do in those practices, knd of advice in terms of the people that send you for second opinions and they may not qualify for clinical research. Bupathi: You know, generally, I just reach out to my colleagues. I'll just say, hey, this is what I'm thinking, and I'll just guide them through whatever, they want to, offer from a treatment standpoint. So either we'll talk about standard-of-care option that may be there. And if it's a new drug they're not very familiar with, I'll give them my pearls. Being like hey, this is what I would do. How frequently I would see the patient, or at least somebody on your team seeing the patient. This is how frequently I would check for labs. This is how frequently I would do imaging. And then, you know, I'll be in the background. If you ever need me to see the patient, just have them come back and see me, and then we'll walk through what it is now. And we may not have a trial now, but I'm sure we'll have a trial at some point where the patient can enroll onto another treatment modality should they need it. So, I think it's that partnership. It's more of like, I'll walk you through, like, kind of in the background if you need help. that's kind of how I've always done it. whether it be my urology colleagues or whether it be my other medical oncology colleagues, because some of our urology colleagues are very brilliant. Like, they know exactly what they're doing, what they're doing, and, you know, it's just a little bit of touch and feel of like, this is what I would do. And then it goes a long way, right? So at the end of the day, we're all caring for that patient and having that best outcome. Garmezy: Yeah. You know, I live in a little different of an island. We have we have over 200 clinical studies. So, we do have a trial for pretty much everyone. Park: It's like a Chinese buffet. You have like 200 items up there. Like we can't compete, man. Garmezy: It's a little bit of a unique spot, but not everybody wants to do a study. So, if they don't want to do a study then that's where that comes in. And sometimes it doesn't make sense to do a study. So, somebody coming over to try to talk about an option and, and maybe the best thing for that patient is going to be belzutifan. Or in RCC, just throwing it out there. Well, then you're going to send them back with instructions on how to take it. That's kind of what I used to do at MD Anderson. When we used to work there, we would have, you know, instructions and, you know, thinking about EPO, right? Something that maybe you're not thinking about giving in RCC, but with that drug, you kind of need to think about it, right? And thinking about it when it comes under 10, just those kind of things that to us seem so routine to you as well, Chandler, but if you've never given that drug before, it's not routine. So, I think if you're a community doctor listening right now and you're not getting that service when you send patients to either an academic or community referral center, you probably should start to think about sending them to somebody else. Because there are, if I think the least thing I mean, you really should be expecting not just, okay, is this patient eligible for my own research interest? But how can they help guide and support the journey, whether it's virtual check ins every 6 months, whether it's just by the phone with the provider, whatever it may be, you need to meet those referring physicians as well as the patients where they want to be met. Because at the end of the day, we are in health care, right? We need to care, make sure we elevate the care for the patients that come to seek us. Clinical trial enrollment is great, but that's not the goal. The goal is the treatment of the person in front of you. And I think that's something that we just have to always keep in mind, because we get so siloed in all of our own careers and academic goals and pursuits. So just something that I always, every single time, it's a phone call, it's an email, whatever it may be. And just going from there. Bupathi: I am curious to know when you guys make recommendations, right? Or even I make recommendations. One of the things I realized is I think it works for me. Like I'll use your example, right? So, I'll say, yeah, belzutifan give EPO. The challenge is the receiving end, right? So, it's like, well, yeah, the recommendation is great, but how am I going to get it approved? How am I going to get paid for? How am I going to how am I actually going to use this drug? And what do I do if the hemoglobin is like normal, right. Are you doing those tricks? You give them those tricks, right. Park: ChatGPT how to get approved. Is that the trick we're talking about? [laughter] Garmezy: He has a little CKD, Chandler. Everyone. Park: Everyone. Right. Just document that GFR is like 59. You know they have CKD. You know that's needs to I think I mean don't quote me on that but CKD 3, right. It's between 30 and 60. So, we'll have to kind of put down this is CKD stage 3. And then emphasize that you know we can't put down GFR 59. Garmezy: Yeah, I mean but you're right. You're right. Your point is well taken. But actually give those little tricks out there for ways to massage the system, not to break the system. But to massage it. Park: And yeah, like those are the barriers like, you know, cost and availability and the reimbursement, like we have a patient right now for prostate cancer. Like we have no funding. So, every year we have to switch, you know like one year they're on Apalutamide. Next year they're enzalutamide. Next is like off-label darolutamide. Then it's [abiraterone], and the patients love it because we fill these grants. But like situations like that, we have to do what's best for our patient care, you know, for prostate cancer. So, you raise a good point. Bupathi: So it poses a different challenge, right? Like, those are patients that could be excluded from a trial because they got exposed to too many things. Park: That's exactly right. But you know, some of the patients, they just don't want any trials. And even though we know it's best for them and, you know, I feel like the three of us were constantly trying to talk people into something, right. We have to talk to urologists to put a stent in right away. We have to talk to the pathologist and say, hey, what percentage of this is truly focal neuroendocrine? All right. Because we might not need like carbo etoposide. And so, it's also with the patients like I feel like there's a lot of stylistic stuff here, you know, and both of you guys are really good. It's like you have to be like, how do I customize? And I think Ben said it best, like in a way we're like in the Hilton Diamond program, right? We have to kind of like help our referring doctors. We also have to help our doc, you know, patients, but we have to do it in a very customer friendly way, you know? What do you think about that, Ben? Like Hilton Diamond, Marriott Bonvoy program. Garmezy: Yeah. No. Realistically though, that that's that's the industry we're in, right? Yes. You live and breathe by how patients put satisfaction scores online, and we comb through those with our team here to make sure that we don't see drops Because people Google our names and Google our clinic. And then the other thing is you live and die by if you're if you're a community specialist, you live and die by the referrals. Right? So at the end of the day, it is something a job that I think if any of the academic doctors are listening today, this is something unique about our three jobs. We didn't necessarily expect that. Maybe you two did. I was naive when I moved to Nashville from MD Anderson. At those places, patients just come through the doors based on the name of the institution. And when you're here, it is relationships and it's and it's experience. And if you've done well with the patients and they like you, and you provide a good service. And the other doctors think you provide a good service. You get more patients and that's how you continue to build a practice. This whole concept of how you were basically a solo businessperson, because even if you're at a large community practice, you are kind of a person of one, right? A business of one that you got to get that in. So, I think at the end of the day, that's a unique part of this job, which actually, I think elevates our care. Because we have to spend time with the patients. We have to make sure that they're happy. And we have to also, you know, make sure that the referring providers understand that we're providing that service. So, I think it actually elevates our care rather than being a downside of the job. Park: Great points. Bupathi: t also gives us a little bit more flexibility, right. Because we're really tailoring our recommendations based on data that exists with some extrapolation of where we think the data is going to go in terms of how we're fitting that patient in front of us. An example. The prostate cancer patients. Can you actually treat them with an ARPI alone and omit the ADT? Are there certain group of patients where you would do that for? Like we don't have strong evidence for it, but are there patients where you can do that? Yeah. There are and would you see a good enough response? Possibly. But knowing that you're adapting to the data that exists, the data where it's going to go and fitting the needs that's there. So, I think that that for us, we don't have to be we're purists in the sense that we understand what's actually out there, but we understand what the data will really look like in the community in the future. Park: And just kind of piggybacking on that, as you know, with the four A's. Like the aptitudeÑyou start writing bicalutamide, everybody will look at us and say you don't have aptitude. So, you have to have aptitude. And then with affability. Like, can I have a beer with Ben? Yes, I can have a beer with Ben. Maybe Sam Adams, I don't know, maybe Bass. I don't know what kind of beer he likes, but I can have a beer with this guy. So, he's got affability. Attitude and also availability. I feel like the three of us, like we're available for our referring base. You know, maybe they call and say, hey, can you see this patient right now? And Manoj is like in Italy right now, he's like, oh, yeah, I can see him next week. And then they're like, hey, your wife is saying, or your family member is like, aren't you in Italy right now? But like that availability piece, right? So I feel like those are the four A's. Now moving along. So in terms of the three of us, when we work with the urologists, right, a lot of these patients with AR pathway inhibitors, maybe they give us a second opinion. What are some of the challenges that you guys have in terms of working with the urologists? When they see the patient, do they automatically bring you on board? Do the patients request a second opinion? What's that relationship with urologists at your practices? Bupathi: I think that that's a that's a tough one to answer. I think it's very much geographic. So, the challenges and the relationships that I have with my urology colleagues is very different compared to you, Chandler, or Ben. And Ben and I have talked about this in the past, you know, when do we get involved? How much do we get involved? And how much do we do when we are involved? So sometimes it's as little as yeah, I agree with exactly what your urologist is saying or your physician saying. And see you later. Check in with me in 6 months. And if something changes, we'll figure out what to do vs the other extreme of, we need to be involved from the beginning, and we're going to do everything, and then it's the other way, right? You'll go check in with a urologist 6 months from now and then se. So, some of that is more disease type, stage, complications, medical complications, toxicity of the drugs that you're using. So, I think it's that really that that complexity goes a lot more into it. To answer your question though, I mean, I think from a prostate cancer standpoint, usually I'll be I'll see the patients up front and then I'll say, see me if you need me. Otherwise, you know, if something were to change, come back. But if they're the more resistant, more advanced prostate cancer patients, then we're looking at like clinical trials or we're looking at more novel therapeutics or newer drugs with toxicities that are not as familiar. Then I'll get more involved with that at that point. And then certainly for the bladder or the kidney cancer patients, then those patients were much more heavily involved because that's more the IV therapeutics. Now, that may change as we see a shifting landscape in more the PD-L1s in the nonÐmuscle invasive bladder cancers and things, as well as injectables for PD-1, for kidney cancer for PD-1 and things. We'll have to see where that goes, though. Park: Ben, what are your thoughts? Garmezy: You know, this is something that actually is near and dear to my heart, this conversation. And you know, with my job at Sarah Cannon, I schedule a lot of one-on-one calls with GU interested physicians that aren't pure GU oncologists at various practices across the country, all trying to get started. You know, they're out of fellowship. They had an interest. Now they're in community practice and they ask advice, right. How do you build your practice? I think it's exactly what Manoj said. Every geographical location is going to have a different level of, I guess, urology program. Right? There's anything from the community urologists, where they don't see a lot of cancer. They do a lot of stents and stones or the larger programs that maybe have some dedicated urologic oncology or oncologic surgeons, but not a lot of therapies. The therapies go to med onc. And then there's places like in Nashville where you have very advanced urology programs, very large practices giving all sorts of advanced therapeutics with an advanced prostate program and sometimes with research in other tumor types. And I think that's all fine. And the key, though, is meeting your urologist with what they need. So, it's developing that relationship, establishing that relationship and understanding the division of labor with that patient. Because we're across tax IDs, we're in different practices. Complex communication is essential. So, in my practice, the hormone drugs for sure are going to be given by the urology group. And they're going to order ADT. They're going to order darolutamide, apalutamide, enzalutamide, abiraterone, whichever one they want. And then potentially if they think they need chemo, they're going to send them over to myself or one of another talented medical oncologists that they're familiar with and ask for 6 cycles of chemo if we deem it appropriate. And then we're going to send them back to the urologist for years. And then maybe they'll give them radioligand, or maybe they'll do that after they, you know, because they have those options, then they'll send them back at some point. And, you know, coming out of academia, we're not used to that, right? Academia, everyone's under the same roof. And the medical oncologists get more of the therapies than the urologists in most centers. And here this works, right, because you have specialty care giving. Med oncs are involved in high-risk patients and in non-high risk patients. They are involved later down the line. But the key here for those listening, right, if you're a community oncologist and you want to build some GU referrals, it's going out to the urologists and not feeling like you're stealing their patients, right? It's meeting them, caring for the patients, providing services that they canÕt provide, providing recommendations when it's critical. Variant histology, higher risk situations. And then allowing the urologists to develop that relationship and then know that at some point that patient is going to need a medical oncologist. So, I think that is critical. That's my advice for all those young community oncologists out there that are trying to build their practices. This is how you can really elevate your practice and develop a little bit of a disease focus, because those physicians tend to like to work with one or two oncologists because they get that dynamic going, and that flow going can almost predict the conversation that you're going to have in a room with a patient. They kind of know what they get when they send a patient over. Park: I mean, you become like the right-hand person, but then you have to build that relationship, you know, and like you mentioned like when you mentor a lot of junior faculty or junior attendings, you know, there's already a process in place before you even showed up. There's already a referral base there already, companies like if you're like an academic institution, but community practice with a urology group, there's already relationships in place. So, you just have to kind of assimilate and then ask yourself, right, do you really want to bite the hand that feeds the referrals? I mean, I hate to say it like that, but like there's already referral in place, so you have to kind of nurture that relationship, so I couldn't agree more. Now what I want to do is I want to kind of switch gears. We want to kind of talk about emerging data and in terms of how does it apply in the real world. So, you know, a good example here is, you know, Oliver Sartor and Scott Tagawa. We got the PSMAddition. And you know some of the highlights is it's a positive study you know. So, first-line metastatic hormone sensitive prostate cancer. The three of us are like looking in the forward in the future. So, it's a strong rPFS, strong overall survival. Let's say that it's FDA approved. So, then the question is how what are the things in terms of the barrier to adopting a new medication, in terms of these breakthrough treatments, what are some of the challenges that you have for new, such as NIAGARA that just got approved in March? What are some of the barriers that you have in your practices? Garmezy: I think one of the, one of the big things is, trying to, get awareness for this, right? So, education is going to be one part. So, when you have a true community partner, a physician that's seeing breast cancer to iron deficiency, to myeloma, to a kidney cancer or prostate cancer and then circle all the way around, that's really hard because these updates that are practice changing are happening in every single field. So, I think one of the key things is education, or at least trying to figure out how do you get the message to those physicians that are seeing these patients day in, day out? But understand that now, the guideline is now changed, and you really need to think about radioligand therapy upfront, not just prechemotherapy. so that's number one. Number two, I think there's some institutional barriers in the sense of pathways, right? So even though we want to be cutting edge, we want to use the new, the latest and the best drugs that are available. There are some physicians who are somewhat limited because they're bound by specific pathway guidelines that they have to pass, or they have to get through. The third is an insurance barrier. So, the data may have been presented like if if the data is presented saying that now you're going to use Pluvicto in hormone-sensitive prostate cancer. And I come back the following day, and I say I'm going to use Pluvicto. I'm not going to be able to do it, because who's going to pay for it? So, there are delays in the system that prevent us from delivering the best care. So, I think one of the key things from our podcast is that exactly. So, we try to take what's the key things and then deliver them out at the much earlier rate so that we can say this is what we're doing to try to get the best for our patients. There's also a resource allocation issue here, not enough radiation oncologists that are authorized users on this drug, right, to service every man with metastatic hormone-sensitive prostate cancer. There is going to be a huge issue with a funnel here. With a limited number of centers providing radioligand and a limited number of slots available at centers that are providing radioligand. So that is just a big complex issue. There are VC firms out there that are trying to jump in seeing a potential market that's complex because that's not part of the practice. Bupathi: The next thing that's going to be that we're going to have to try to figure out is which patient we're just hitting on, then is which patients are going to be the ones that are going to get radioligand, which patients are the ones that are going to get triplet, which patients are the ones that are going to get doublet, and which patients are going to get the park right. So now you have many different options for hormone-sensitive metastatic prostate cancer as opposed to everybody gets an ARPI and everybody gets an ADT like. I think we're going to have to try to figure out or at least provide some guidance to our colleagues saying, how do we actually look at this or think about this, from which patient should get which type of therapy? Now that's the data that's not actually ever presented. No one talks about, you know, how you know, like how are you going to pick, right? Like how are you going to pick the triplet with docetaxel and darolutamide vs just ADT with darolutamide and without chemotherapy and then give them to us. That's not on any podium. Park: Yes, I agree. I think the liver mets subpopulation in the area kind of concerns me a little bit. But I mean to your point, like the SUV, if it's above 40 median for everybody, you know, maybe that would be a slam dunk, And then the question is if we give them, you know, Pluvicto and they have a BRCA1 and BRCA2, now you're giving two medications sequentially in whatever order you want that's going to cause bone marrow suppression. And so those are the things we talk about these long-term consequences of a combined shared toxicities that the patients might have. So, you guys raise a great point. So, any lasting thoughts on future directions? we'll have Ben go first. You know, he's like a Renaissance man. Like he can look into the future here. Tell us about future directions. Any closing thoughts? Garmezy: I think future direction is we're going to see more research, more drug development, moving away from academic centers to centers like all three of ours. Right? Norton, Sarah Cannon in Nashville, Rocky Mountain Cancer Center. And the reason for that is that's where 80% of patients are treated. Pharma is needing more and more FDA guidance that we need US accrual. And the way to get US accrual is to bring your trials out to the community. So, I think we're going to see that, which means all of us have to train our colleagues how to become subinvestigators and principal investigators. Park: I love that point. What about you, Manoj? Bupathi: I think a lot of our colleagues are going to look to us to help guide therapies and how we pick therapies, how we manage some of these toxicities. When do we think about a trial for some of these patients vs going with the standard of care, which may be a very good option because trials may not always be the best option. So, I think that's where we're going to be seeing and certainly very exciting to be in GU right now because of all the new therapies that are coming about so well. Park: I'd like to thank everybody for this discussion tonight. I love this discussion. So, you know, if you want to learn more, Oncology Decoded, Manoj and Ben really get into the data. I've listened to the podcast very engaging and very informative. So, all right, until next time. Thank you everybody.