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We are really honored to have Dr Jason join us today and we're going to be talking about advance of prostate cancer. And we're going to be covering one learning objective, which is appraise and apply clinical trial data to clinical practice. Doctor da Thank you so much for joining us today. My pleasure, great to be with you. Uh What we like to do in these um sessions is, is actually frame what we're doing around a patient. So we've got a little vignette of a case which is a fictional case at the start of this conversation and we're not going to dissect it line by line, but it, what we want to do is actually frame some of the conversation we're having today around how that applies to patients. And here's a little case that, that we've written, which will hopefully give some context to the questions that we're going to have today in, in our discussion. And the case is this James, a 65 year old former athlete was diagnosed with advanced prostate cancer that had metastasized to his bones and lymph nodes and given the aggressive nature of his disease, James sought the expertise of Dr Da, the leading urological oncologist reminded for his innovative approach to integrating emerging therapies and surgical techniques. As James and Doctor Da navigated the complexities of his treatment. They faced numerous decisions shaped by the latest clinical trial data and advancements in advanced prostate cancer therapies. And so what this case really highlights is the evolving landscape of prostate cancer treatment, encompassing integration of new therapies, multidisciplinary collaboration and the application of clinical trial findings to real world settings. And we're really excited to have a conversation with you today, Dr Deson about um applying and appraising clinical trial data in clinical practice. I guess what I'd love to chat um to start with is is about emerging therapies and surgical considerations. Um Doctor Gleason with the rapid pace of advancements in prostate cancer therapy, uh particularly with uh par I and T cell targeted immunotherapies. How is your surgical approach to patients with advanced prostate cancer evolving? Uh So just to start with um what I wanna make really um a point of saying is that we presently don't have a role for surgery in the standard of care in the patient with advanced prostate cancer. So, you know, I if this is um kind of a discussion about the present standard of care, I would say that it's something we really should undertake with caution. Now, that being said, there's a lot of enthusiasm for the role of surgery in the advanced setting and this is the subject of a number of different clinical trials. Um some of which we are participating in, some of which we eagerly await the report of. And I think we're going to see that this is a large component of the future in how we address prostate cancer. So um when it comes then to thinking about specifically integrating them with the treatments that you discussed, um again, I would say that really is in the realm of a clinical trial. Um There is a current um multiinstitutional clinical trial that we have open and it's probably open at the majority of academic centers in the US. Um which is a swab study focused on looking at the role of local therapy following the best standard of care, systemic therapy um for patients with newly diagnosed hormone sensitive metastatic prostate cancer. Now, in that setting, the current standard of care does not include either a parp inhibitor or treatment with um you know, any T cell directed therapy. However, that is potentially changing. Certainly in the second line option, especially if a patient has a germ line or somatic alteration in a DNA damage response gene. Um parp inhibitors are, you know, quite a standard T cell directed therapies are a little bit less commonly employed in prostate cancer in the clinical trial setting. Although I know of, you know, some emerging work in that area, I'm not aware of clear um availability or clinical data to support um the use of the T cell directed therapy. However, we've seen a marked um kind of surge in how important these are in the treatment of, for example, hematologic malignancies with both T and NK, you know, directed chimeric therapy. And so I'm really hopeful um for the promise of them being applied to the prostate cancer setting, but currently kind of in the realm of early phase studies. Um And so I think the, the, the parp inhibitors with our recognition of how important the DNA damage response mechanism is in prostate cancer is kind of rapidly becoming a standard of cure, but generally speaking in the second line or beyond setting and um that may change but is currently a little bit difficult to integrate with surgery just because of the slightly different phase at which he's just applied. And do you think we're at the point perhaps, perhaps not based on what you've just said? But are there any situations where you might consider delaying or modifying surgery based on any of the emerging clinical trial data for these new therapies? Well, you know, if somebody was, for example DNA damage response gene altered, whether that's in the somatic or the germ line, um I think that we know that they're gonna potentially have more options and some of those more options, you know, are gonna include parp inhibitors, but also potentially then um platinum based therapy down the line. And if it were the thought of enrollment in one of these trials where we're focused on local therapy and surgery where the local therapy, um, I would probably be a little bit more hesitant to enroll those patients for two reasons. One is that you have more systemic therapy options down the line. And so then we're adding treatment upon treatment and you wonder about, you know, um, how all of these treatments are going to then, uh, impact quality of life at the end of the day. And the second being that the DNA damage response gene alter tumors where these therapies are used, tend to have a slightly more aggressive course, tend to have a slightly um higher likelihood of having more metastatic disease than the illegal metastatic population. And so for that reason also, so I'd be a little bit hesitant to um pursue local therapy. So yeah, it, it would kind of be um perhaps an indication against rather than for, although this is a bit of a new landscape and understanding how we're going to properly integrate it. Um moving forward, it's, it's gonna be a, a kind of decision shaped by upcoming clinical trials. Sure. Um and with all of this, you know, this is a fairly rapidly moving space. Um from an integration perspective. What sort of barriers are there to implementation of, of these new treatments in uh prostate cancer? Are there issues of accessibility depending on the setting of the healthcare professional or patient, how can we overcome them. Do you have any examples, I guess, from your experience? Yeah, I mean, market, market barriers, um, you know, this is a real challenge with healthcare delivery, um, across the world. I mean, it's not just in the US but, but across the world for sure. But certainly in the US. Um, you know, the big thing I would, I would phrase it that there are a few different aspects to this. So I guess there's the patient aspect. Um and then perhaps there's the drug aspect and the actual medical aspects of it. And then maybe there's the, you know, healthcare provider, institutional aspect of, of these access barriers. So I guess from a patient perspective, I mean, prostate cancer, uh a affects the whole um spectrum of our population. Um you know, prostate cancer as, as you may know, is much more common in men that are black and they're much more likely to pass from prostate cancer. And that often correlates with um socioeconomic disparities also. And so um if you add socioeconomic disparities, you add racial disparities, you add insurance status which plays into that mix, you add financial burdens. Um That's a big factor here. You know, I was just reading um in the Wall Street Journal today. Actually, an article about the financial toxicity of cancer treatments and something like uh 50% or more uh cancer treatments that have been approved in the last five years are on the cost burden of about $200,000 or more per year. And if you look at $100,000 or more per year, that number is like 80% of all cancer treatments in the last, you know, five years or so. So, the vast majority of prostate cancer treatments would fall into these, you know, expensive medication category. And patients um you know, often have some form of insurance. Um, patients with prostate cancer tend to be above uh you know, 65 or so. So, so Medicare isn't, um you know, is a common insurance, but um we see a lot of patients that are under 65 with advanced prostate cancer and some of those patients may not have insurance. Some of them um may have uh you know, private insurance with a high deductible and the financial toxicities of some of these things are, are marked. Um And even though, you know, you say, well, the sticker price is $100,000 a year or $200,000 a year, um the out of pocket price may be much lower for a patient. But, you know, I I'm pretty sure there's data to say that the average American is essentially living paycheck to paycheck. And so when you throw on there, you know, a medication that might cost $500 or more a month, even if that's a marked reduction from the sticker price, you're gonna have huge um patient related financial barriers. Um So there's the financial aspect of it, there's the educational aspect of it. Um, just the idea to seek treatment for some of these things to pursue cancer screening, which might mitigate the advanced stage of diagnosis if it were diagnosed earlier. Um, the idea of, you know, pursuing care at a specialized center where you may have access to both the best standards of care and um you know, the best options to assist with achieving the medications, whether it's financial assistance, whether it's just navigating the complexities of the healthcare system. Um You know, those are other patient factors there too. Um from a medical end, I mean, these drugs, um they have toxicities and they have monitoring requirements and they have different routes of administration. Um you know, for example, there's been a move to move chemotherapy, um you know, to a larger proportion of the patients diagnosed with advanced prostate cancer. Um This originates um firstly from data stating that triple therapy, namely treatment with androgen deprivation therapy, a novel hormonal agent and DOCEtaxel is beneficial for patients um predominantly with the high volume uh synchronous metastatic disease state. Um That is a bit of a shift in that. Now, patients have to kind of firstly see multiple different specialists. Um namely oftentimes, it would be a urologist and a medical oncologist for the receipt of the DOCEtaxel. Um medical oncology is an uh a particularly difficult um kind of access issue in our communities, mainly because we are quite rural across at least the state of Ohio. But a lot of the US, um the medical oncologist is quite a specialized, um you know, resource and a lot of the time a medical oncologist working in a small community will have to navigate a large number of different types of cancers. Um A large number of different types of medications nowadays including chemotherapy, immunotherapy, hormonally related agents. Um And so that barrier there in moving the chemotherapy up to achieve the best standard of care is certainly another difficulty with access, especially because I think that the idea is patients will not just be getting a shot every three months as they might have, you know, 10 years ago. Um by the small town community urologist, um we're talking about a shot every three months, but now with the addition of cytotoxic chemotherapy in a large group of patients, which is certainly we know improving survival and good for patients but will be an access barrier. And additionally, these novel hormonal agents which again are not as simple as the shot in the mo you know, kind of every few months um are gonna require monitoring, for example, in the setting of abiraterone liver toxicity, uh electrolytes, use of the predniSONE and implications there. Um markedly increasing the medicalization of what is a very common new cancer diagnosis and for the patient without easy access to, you know, subspecialty providers, um that is gonna be a another issue there too. Um And then, you know, looking at like the provider and the institutional level uh keeping up to date is, is challenging. Um And that's going to mean reduced access um for patients because things are shifting so rapidly. Uh We're seeing, you know, every meeting now shift the standard of care slightly, let alone things that, you know, are outside of the standard of care, but will be coming into the standard of care such that, you know, one can stay up to date even beyond what the latest guidelines say. Um that rapidity of progress is really hard to keep up with because most people are not just seeing prostate cancer, this is happening across the board. It's happening in urothelial cancer, it's happening in renal cancer. And so, you know, for an individual, even genito urinary oncologist to stay up to date with the latest treatments um to be able to provide that, you know, optimal access to patients is is difficult. And so, you know, ii think wherever you hone down on it, we're seeing challenges and with challenge, you know, everybody wants to rise to the challenge. And so there's new and new solutions to come up with this um for how we can best approach it for the betterment of, of all patients. Um but um certainly it, it, it is a big access challenge with the progress of the field. Sure. Um and I guess in that seems sort of vain um in your experience when you're looking at clinical trials for advanced prostate cancer therapies, what are some of the most critical criteria you consider to ensure the generalisability and the applicability of the findings to your patients in a real world setting, right? Because we've got lots of different factors at play. Yeah, for sure. Um So the one thing I would say, y yy, you could, you could take a few different um tracks with this. So one big thing in prostate cancer is to make sure that the clinical trial population is representative of the population diagnosed with prostate cancer. And for this, I'll specifically speak about black men being under recruited to clinical trials. Um because again, we know that black men are about twice as likely to die from prostate cancer in the US. And um you know, about 60% more likely to be diagnosed with prostate cancer. Um It's really important that they're represented in the clinical trials. Um you know, for new treatments so that we can understand, is there anything different, is there anything you know that we have to consider specifically in those populations as well as just equol access to the latest um treatments? And so I think that that's been in the last few years, a big and important movement um to ensure representation. And so, you know, I I've seen a lot of recent data um emphasizing the diversity of the patient population. Um a and, and how that, you know, kind of uh played into both study design and reporting of results. And I'm glad to see that because again, um that is a large demographic of what prostate cancer afflicts in the US. Um And so that's one aspect of it, the other aspect of it is truly uh conducting trials and reporting trials in clinically important populations that are reflecting the current standards of care. So by that, I mean, um and this is not a fault or a flaw of the clinical trials that have been reported recently because they were designed, they were conducted with the best available understanding at that time, but we are limited in applying the findings of some of these clinical trials because the field has changed. And so I'll speak about a couple of specific examples. Um PS ma pet scans have markedly advanced our staging of prostate cancer. Um I suspect that across the US, across the globe because actually globally um there were numerous other leaders in PS ma pet scanning. Well before it was approved in the US, namely Europe, namely Australia, um you know, a all sorts of um great work that came out before we had access to it. But the point is that we were one of the last um developed nations to adopt PS ma pet scanning and it has been adopted and is currently quite a standard. The challenge is that when we look at clinical trials, when we look at definitions of how disease states are defined, when we look at maybe the populations um where benefits have been reported. These are all generally based on conventional imaging and we don't know if the increased sensitivity that is afforded to us by PS ma pet scans, um allow us the same generalisability of those clinical trials, for example, in non metastatic castration, resistant prostate cancer. Um we have evidence for the use of anti-androgen novel anti-androgen agents. Um you know, but those were studies conducted before ps ma pet scans. And so is that same data applicable when we stage patients with ps ma pet scans. For example, another great example would be we currently use very much. So a part of our decision making um the high and low volume definitions from the charted clinical trial to define how significant someone's prostate cancer is. And so if somebody has visceral metastases or they have bone metastases, at least four of them with one of them outside the axial skeleton, that patient is classified as high volume metastatic um prostate cancer. Now, um in that clinical trial, you know, they used that stratification, it was a little bit arbitrary. Um but that has been a stratification that's now been adopted, moving forwards in a number of other settings to allow us to understand how we should treat patients. But that was just generally based on conventional imaging, namely CT scans and bone scans and not the PS ma pet scan, which we use as a standard. Now. So how do we apply that definition? How do we apply those clinical trial data um with our modern imaging, for example. So you know, um I think that it's clear we're gonna update the clinical trial inclusion criteria to include modern imaging, et cetera. And so you know, the trials we report in 35, 10 years are going to be reflective of our current standards of practice. But the difficulty will be, where will we be then? Um and how you know, will kind of the future trial results apply to the standard of care then? So I think what's most critical is, I guess now to have fluid criteria to no longer use old criteria because if we use old criteria, we're already, you know, kind of burdened by the trials being not applicable now, right? Um I guess one of the other uh advances in recent years is the use of biomarker strategies. Um And recent clinical trials have explored the kind of optimal sequencing of systemic therapies for metastatic castration resistant prostate cancer. Can you discuss the challenges you might face in making these decisions? How do you see promising biomarker strategies evolving to personalized treatment um sequencing based on on recent clinical trial data? Yeah, I mean, prostate cancer has always had a really great association with the use of biomarkers, namely because we're talking about psa being, you know, kinda hand in hand with prostate cancer for the past few decades, whether it's the screening setting, whether it's the um posttreatment followup setting, whether it's the assessment of response in the advanced disease setting. P SA and prostate cancer go so well together. Now, um what I suspect you're talking about though are novel predictive biomarkers to indicate specific treatments. And in that setting too, at least amongst you, cancers. Prostate cancer is a real leader and prostate cancer researchers rather have been real leaders um in developing these treatments. Um And so at the present time, there are two critical predictive biomarkers that inform treatment decisions and are part of the standard of care. So the first one is part of a penance approval for immune checkpoint inhibition in patients with um basically mismatch repair deficiency, um MSI high status. Um you know, they don't all have Lynch Syndrome, but patients with Lynch syndrome will often have this status. Um and so effectively, if somebody has a tumor in any site with um mismatch repair deficiency, um it is known that there can be responses to immune checkpoint inhibition, namely with pembrolizumab. Um And so this is something that we use in the clinic in prostate cancer. If somebody's tumor has, you know, significant mismatch repair deficiency, one can detect that when you do um tumor related genomics and that can then indicate um response is is reasonable to um keytruda or pembrolizumab. And so, the challenge here though is that it's not a common um alteration. Uh I'm aware of data supportive of about 3% of prostate cancers having mismatch repair deficiency. But when you find it, it can provide a really important therapeutic opportunity because of the predictive biomarker there. So that's one uncommon but can be critical in some circumstances. Um The second one which is receiving a lot more but it is a lot more common um is really DNA damage response gene alterations, which we're speaking about a little bit earlier. So the specific, I guess best data is really for pathogenic alterations in BRCA two and BRCA one, like slightly less. So BRCA two being the more aggressive, more um likely to contribute to prostate cancer. Um but also across the whole spectrum. Um you know, there's something like 2530 DNA damage response genes um which can be altered in prostate cancer for which pathogenic mutations are known. The challenge of course is outside of the bra specifically BRCA two. We will not be as able to understand how truly important, you know, a less common gene alteration is as a predictive biomarker just due to limitations in data and numbers. Um But at this point, all DNA damage responses, gene alterations with pathogenic mutations are probably reasonable to be considered predictive biomarkers for response to a parp inhibitor. And so in the, you know, usually second line settings. So castration, resistant prostate cancer setting, um parp inhibition in the patient with either a germ line or somatic alteration in DDR is a really critical and important um option. So, um I would still say that those are, you know, relatively in their infancy compared to some other cancers like breast and lung where I feel following those fields, um predictive biomarkers, genomic biomarkers are even more developed than in prostate cancer. But I think that probably tells us, you know, the future is bright for further management in prostate cancer because a lot of interest is is underlying the development of these, right? Um Really hot topic. So um clinical trials often put focus on the efficacy in the short term, right? Um How do you factor in the potential for long term toxicities from particularly emerging therapies when evaluating the clinical trial data? But also in discussing treatment options with your patients, considering kind of their goals and preferences for advanced prostate cancer. Yeah. And you know, that's one of the difficulties in prostate cancer research and prostate cancer clinical trials that sometimes doesn't come to the forefront. Uh you know, of, of what we discussed because prostate cancer is a very, very um much longer course than many other cancers. Um The survivals we see in advanced prostate cancer, even in the metastatic setting where the latest studies will report median survival of five or more years. Um really eclipse many other cancers like lung cancer or pancreatic cancer or you know, other cancers where you are not gonna have a length of life long enough to see the long term toxicities of treatment. And so survivorship, I guess, you know, it, it's a bit of a definition matter as to whether you'd call it survivorship, given that patients are living, you know, potentially still with the cancer. But these quality of life issues in a sense, mirroring survivorship is an important part of any new treatment we apply. The other part of it is that patients with prostate cancer when they're in the advanced setting may often still have the lingering toxicities of treatment from their primary prostate cancer. Um, if they have, for example, a metachronous recurrence, and so, you know, men that had surgery for their prostate cancer are still gonna potentially be dealing with the urinary and sexual function issues originating from that surgery. Similarly, the radiation treatment that they might have perceived that was not successful might still have lingering effects. So you're kinda having then compounded effects of the systemic therapy and potentially their past history. Um And then you add to that, that the average age of prostate cancer patients with advanced prostate cancer is gonna be into their seventies. A lot of men are gonna have comorbidities and other things that are gonna interact with these treatments. So the best way I think to properly address this is really going to be with the right metrics and clinical trials. Um It's a fairly standard, you know, thing in in modern clinical trials, the quality of life and the patient perspective is is critical. Um patients often sit um on the design committees of most clinical trials that you know are are being conducted in in a multicenter fashion um to lead to approval of these new treatments. And so as a result, health-related quality of life metrics are often reported hand in hand in many large clinical trials and again, not exactly the advanced setting, but sometimes, for example, in the protect study, which is a large um localized prostate cancer study coming out of the UK. Um that has been reported a few times in the New England journal, you know, you'll have a partner study, the survival outcomes being reported in one big paper and the quality of life outcomes being reported in a second big paper. And so with these, you know, patient focused patient centric metrics, namely health related quality of life, we can properly assess what the value of these treatments truly is, not just length of life but quality of life. And then, you know, you can also assess potentially um the financial aspects of it as a third kind of pillar given the increasing costs of these treatments as to whether it's actually beneficial for, you know, a quality associated life here, for example. So um I think that yeah, clinical trials are increasingly comprehensive in assessing these things in that it's not just about median survival. Um and the Kaplan Meyer curve. It's about all of these health related quality of life metrics. Um prostate cancer being a big, big um I guess model for that, given that yes, patients live quite a while and um quality of life is as important sometimes as quantity. Sure. Um I'm gonna squeeze in uh one last question on visceral metastases. Um And recent clinical trials have yielded some of your insights on managing advanced prostate cancer with uh visceral mets. Can you elaborate on how this data has impacted your treatment selection for these patients? And are there any specific challenges that you encounter that require a little bit more research? Yeah, I mean, you know, before about five years ago, with the changing standards in metastatic hormone sensitive prostate cancer, you know, if you had metastatic um hormone sensitive prostate cancer, you were just basically put on a DT until you progressed on a DT. It was in a sense, very simple. Um But in another sense, a bit simplistic. Um what we really learned with the report of a couple of big clinical trials um namely charted and Stampede uh you know, kind of 67 years ago or so. Um was that yeah, these patients of de novo metastatic hormone sensitive prostate cancer are really um quite a diverse bunch. And so I think that the current way we stratify patients incorporates visceral metastases. Um quite uh uh kind of critically in that if a patient has either visceral metastases or um four or more bone metastases with one outside of the active skeleton. They're considered high volume by this charted definition that I think has become kind of a relatively standard definition, at least at this point in our field. Well, if they don't have visceral metastases or they have, you know, kind of n that negative bone metastases criteria, then um they would be considered low volume. And based upon that we actually apply quite a few clinically relevant treatment stratification. So for example, those with high volume receive often triple therapy that is at diagnosis, they receive a DT DOCEtaxel and a novel androgen axis, uh manipulator, the low volume. Meanwhile, often receive double therapy that is they receive a DT and a novel hormonal um manipulator but often don't receive DOCEtaxel upfront. Additionally, those with low volume metastatic hormone sensitive prostate cancer often will receive radiation treatment to the local area because there's data from Stampede to support a benefit in the low volume patient population. So, um yeah, the visceral metastases is one of the big factors playing into that. The other way that it plays into our management is if somebody is really progressing on treatment, especially with visceral metastases, new liver metastases, and especially if their radiologic progression is out of keeping with their P SA progression, we will often start to consider that they're developing a neuroendocrine phenotype and that may then lead to a biopsy of these visceral metastases and if you find the neuroendocrine phenotype, um we really will often wanna shift strategies. Um These phenotypes are kind of much more sensitive to chemotherapy than further hormonal manipulation or further um conventional prostate cancer directed therapies. And so that's another real arena where you know that visceral met that's progressing with P SA remaining stable, um plays into treatment planning and decision making. Doctor Dyson. Thank you so much for your time today. Um We've covered so much in such a short space of time and we're really grateful. Thank you. Yeah, it was my pleasure. Ok, I'm gonna do cut just there. Uh Sean. Um Thank you so much. That that's brilliant. Um We uh we have a little bit, um we have a little bit more to cover in terms of the second learning objective, but I realize we're um we're at six, we're, we're at 45 minutes past the hour. Um So I don't want to take up too much of your time, but if you've got a little bit more time, are you happy to, are you happy to do the second learning as well? Yeah, perfect. Um That's really brilliant. Some really great um um uh kind of topics there and um and yeah, covered, covered, I think you've covered it really well. Actually I think there's stuff there that if I'm in primary care I can dive into. If I'm a oncologist I can dive into and, you know, I think some of it will spark a little bit of debate and so on as well, which is great. So, um so that's, that's perfect. Um The second, the second learning objective um is a little bit um more about the kind of practical implication of um and the practical implementation of um kind of treatment regimens, we'll touch a little bit on um uh kind of implementation in diverse settings as well and strategies to do that. So it's uh I guess, slightly less uh trial and um research focused and more kind of implementation and the practicalities of that. So um what I'll do is I'm just gonna start again as if this is a whole new session, but we're, we'll talk this video into um and I'll do the same thing. So I'll talk to you a little case at the start and then we'll dive right in if that's OK. Yeah, sounds great. Super, we're really honored to have Doctor Jason join us again and uh we're really um grateful for your time. Uh Thank you so much for joining us. We're going to talk in this session about planning for clinical implementation of treatment regimens. And as we like to do, we like to frame things around a patient. We like to take this discussion and to give you a, a case vignette to really think about how we take this discussion and implement it into clinical practice. And we've got a little bit of a case scenario that we've written to kind of frame our conversation here today. And it's about Samuel. Samuel is a 72 year old retired farmer living in a rural community and he was diagnosed with advanced prostate cancer and his local healthcare facility lacked the resources and specialized expertise available in urban centers, presenting some unique challenges in managing his condition. So recognizing the need for comprehensive care, Samuel's primary care physician referred him to Doctor Da. Uh he was renowned for his innovative approach to implementing new treatment regimens across diverse health care settings. And that case vignette really is a bit of a springboard for our conversation today and how we implement changes and how we overcome barriers and how we use a multidisciplinary team to navigate some of the barriers in in health care and make sure that that patients receive the most critical therapies for their advanced prostate cancer. So, Doctor Deson, you've highlighted previously the importance of recognizing the diversity in healthcare settings and identifying some of the barriers that might exist. I really wanted to ask if you could share some potential strategies that you've employed to try to overcome some of these barriers. Yeah. Um you know, this, this is a really important topic that resonates closely with me because I feel like it in the vignette and in the description of what's going on is clearly a reflection of our patient population here in Central Ohio. Um You know, I'm located in a metropolitan area with about 2 to 3 million people in about a 45 minute radius. But we geographically cover um patients, you know, 23 hours south, 2 to 3 hours west. Um in, in a sense east also where they're coming from both a large distance, as well as a large gap in access to any other kind of ancillary services as well as sometimes also socioeconomic disparities that can exist in these rural settings. And so I see these challenges, I guess on a very regular basis, and I'm always um working on how we can kind of figure out maybe the best care for the patient in, in light of these challenges. So, um yeah, strategies to work on this. Well, I think one huge huge strategy has been telehealth. Um you know, before the COVID pandemic, um we very rarely did telehealth. In fact, I would say that there was essentially no telehealth as part of our practice. Um There are a few reasons for this. I think one of it really is cultural. Um It just wasn't part of the way that we practice medicine, you know, pre COVID. Uh The second really relating to reimbursement. Um There was no financially viable way to do that in our healthcare system um without the telehealth kind of being written off. And so, um that I guess shifted markedly with COVID. And so I think that was a really big step forward in cancer care that originated from, you know, a challenging situation, of course. And so, um, now I feel like it is the routine that, you know, a quarter of our clinics are done via telehealth at least a quarter. Um And so for patients without the ability to take the day off work and make the two-hour round trip, which means it's, you know, at least half the day traveling, um you know, to come into town to see us for a routine visit. This has really allowed um us to kind of deliver that care quite effectively at home. Now, um of course, that doesn't apply to every situation, but it can often be quite effective in the patient with prostate cancer where it's just a routine visit. They might need to just complete some labs locally and check in with you. Um This would allow for um real kind of uh access there in these rural settings. Now, not just that, but it also promotes a little bit the centralization of care because for the patient who is hesitant to pursue care um at a setting like ours where, you know, we do have access to some of the greatest and latest and greatest um options. Um The idea that they would have to travel very, very regularly um For that care is often a, a big turn off while the knowledge that hey, some of it could be delivered by telehealth where appropriate is a, is a huge potential benefit to this patient population that is hesitant on the travel. Um The other strategy that I think works really well is partnership with local healthcare providers. So it is very uncommon for a patient in a rural setting to have no healthcare provider um that can address their need. I think the bigger challenge that we see at least is that the healthcare provider locally may just not have the same familiarity, expertise and comfort with the advanced cancer setting that they may be experiencing. Um But of course, these are still often excellent healthcare providers located in a place that's much more convenient for the patient. And so I think that a partnership in some fashion is really the key to delivering the best care in these rural settings. Um as an example, um patients in our rural settings um will often have access to a local urologist or a local oncologist that might be, you know, two or three hours closer to them than coming to our center. But that local urologist, local oncologist may not be familiar um with some of the latest treatment, indications with some of the latest testing and maybe what the best first steps are. So what's very routine is for a patient to come to see us for an initial consultation. Um Often a multidisciplinary consultation um myself on the surgical end, um a colleague on the medical oncology and a colleague on the radiation oncology and um for recommendations and they may or may not then actually receive all of their care at our center depending on what they might have access to locally. So I feel like on the surgical end because it's often a one and done thing. Um, once they've recovered and a lot of the time, depending on the surgery being proposed in the cancer setting, the local urologist may be less able to deliver that locally. Um, the surgery will often say happen at our center, but then let's say they then need um postoperative systemic therapy or some other, you know, thing that pops up down the line while the consultations and recommendations may originate from, you know, a one time visit or uh back and forth a little bit after a bit of testing. Um They could often then follow up with a local medical oncologist um for receiving that ongoing treatment and perhaps revisit at the time of progression or revisit at the time of significant toxicity to figure out maybe how we can move forwards um in these selected settings. Sure. Um I guess the other, the other barrier that we've kind of discussed is resource allocation to um be able to afford some of these life prolonging treatments. Um How do we, how do we go about achieving that kind of long term sustainability? So that actually some of these life prolonging treatments for people with advanced prostate cancer are widely available? Um What, what can we do within our healthcare systems to begin to achieve that. Yeah, I mean, that's a real, real, um, big can of worms. And it's a challenge because it's something that we see on a day to day level in the oncology setting. Um, at this point in time, you know, most patients that are receiving cancer care will have some form of insurance. Um whether that's Medicare, Medicaid, private insurance, some sort of other governmental payer like the veterans system. Um And so the, I mean insurance, um, availability has markedly gone up in the past 10 years with shifts in the healthcare system. Those that are uninsured are certainly a target population. But the good thing is that with Medicaid expansion and with other options, at least that we have at our Center for Charity Care and Grants, um, that is increasingly a shrinking population which is at least one positive light for progress being made in access to cancer care. The challenge is that even with insurance, the sticker price on medications on other treatments is so high that a 10 or 15% coinsurance is a significant financial burden for people. And, you know, many Americans, um especially in rural settings and settings where, um, job access to high paying jobs is lower et cetera, uh, live paycheck to paycheck. And with uh, cancer treatment, it wouldn't be uncommon for there to be an out of pocket cost of 5 to $10,000 a year for patients to receive the best care. Um and that might be a low end estimate with reasonable insurance. And so if you think about it, you know, that is a marked financial burden for the average patient. Um Yes, there are gonna be some people that will not have financial stress, but there are gonna be many people for which that is a dealbreaker and they actually will then have to choose to prioritize that their spending be placed elsewhere and that they not receive the best standard of care because it's just too expensive even with insurance. And so I think that that's really an avenue for where we can make big inroads. Um You know, there are often granting or costing programs that companies have um where the drug cost will be reduced and the copay and the coinsurance cost will be reduced through a special application. Um But the problem is that those are not universally accessible. Um You know, it requires a little bit of insight, a little bit of navigating the system if you will to be able to access some of these things. Uh Additionally, there are other financial assistance programs and I'm fortunate to work in a center where, you know, we have good um facilitation of access to some of these things. But um that's uh again, it's a, a sense of navigating the system which can be quite difficult to navigate at times. And so I think it would ideally be, you know, if we had a um magic system where we could just fix it so that pe people don't have to navigate how to access financial assistance. So they don't have to navigate how to access cost reductions. That would be great. But um ii just don't know what the perfect solution is and I don't think we're anywhere close to figuring that out, especially with the increasing costs of the treatments in general. Um It's gonna be passed down in some fashion to patients and it's not like, you know, patients are having any easier time in affording these. So, um uh I think it's gotta be multifaceted. We're gonna need legislative work, we're gonna need medical system work, we're gonna need, you know, insurance system work um to really help with this issue, I guess, I mean, we've, we've chatted previously about the role of academia and clinical trials in prostate cancer. And this is an interesting area, right? Um Where do you see the role of academic research particularly in influencing practical clinical approaches in treating advanced prostate cancer, particularly in diverse settings? Should we do? We need to do some trials in this space? Yeah, I mean, I think that a lot of our trials are focusing on the latest and greatest agent they're focusing on, you know, we talked about earlier parp inhibition and T cell directed therapies and these medical advances are clearly remarkable. Um And they're clearly getting the press and the buy in that they should. But on a practical level, prostate cancer, it's the most common cancer in men. It's afflicting a lot of men across diverse settings. We're seeing an elevated risk of diagnosis and death amongst black men. We're seeing axis challenges in rural areas. We're seeing all sorts of disparities in care and that definitely does not get the press that it needs and definitely does not get the clinical trial attention that it needs. Um And we really don't know the answers to some of the questions that you've been asking me in that. How do we best care for patients in rural settings? How do we best minimize the financial toxicity and burdens that people have so that they can get the best access to care. How can we afford this all as a health care system? Um And I think that those are probably the best areas for us to conduct clinical trials and then for us to do future research in because they're really the most practical questions that need answering, you know, in advanced prostate cancer today because of every single advanced prostate cancer patient is on treatment with an A DT with something novel hormonal active agent and DOCEtaxel. And they're getting tumor and genetic uh germline testing, you know, a and then they're going on to get PS ma pet scan and then they're gonna go on to get, you know, luteum ps ma pet um agents and then they're gonna get maybe a parp inhibitor and this and that and you know, this is a marked advance for prostate cancer care from a scientific level in that we've got all these options for patients. But yes, how do people access it? How do people afford it? We can come up with these kind of back of the napkin ideas. But we really do need clinical trials in these settings. And uh kind of final, final kind of topic from my side is thinking about standardization and um variability and variability variability exists in how we all approach our patients, right? And how we approach treatment. And I guess how can we be leveraging some of the recent clinical trial data or should we be doing so to develop standardized protocols that maybe allow a little bit of flexibility for patient needs? But ensuring that we are delivering evidence based care for advanced prostate cancer particularly across those diverse settings. Should we be trying to put a push more on standardization or do you think we're about right, in terms of the amount of flexibility that we uh facilitate? I guess as a multidisciplinary team? Yeah, I mean, I think it's hard to say because on the one hand, flexibility is key because you know patients at the center of their cancer journey and you really need to focus on making sure that all of your care is patient centric and within what they would wish for their goals and their quality of life and you know, et cetera. On the other hand, we're probably seeing marked heterogeneity in how patients are cared for. Just because of limitations in knowledge, limitations in the dissemination of the latest research, limitations in access to, you know, to therapies that are not exactly the kind of flexibility that we want that guideline discordance per se. So the right, I guess ideal way that we would deliver care would be that it's patient centric and that there's flexibility to deviate from the guidelines, you know, when it's appropriate um to maximize the patient uh quality of life and experience, but also minimizes um these other aspects that are not the kind of variability and flexibility that we want. And in all honesty, I mean, I think that this is where A I in the next few years is really going to um allow for this because, you know, if you look at the latest NCCN prostate cancer guidelines, um and you weren't up to date. Uh Let's just say you were a prostate cancer specialist from four or five years ago, you wouldn't recognize them, you wouldn't have any idea what's going on because the field has just changed. It's so different. Now, um the way that one approaches anything is totally different, turned on its head than, you know, five or 10 years ago. Um you know, when I was in training in castration resistant prostate cancer, there was one, you know, chemotherapy option, DOCEtaxel and you know, two clinical trials we have to know about and you know, that, that single option, extended life by three months or so. And that was it for castration resistant prostate cancer. And otherwise it was just a DT and, you know, it, it, it's now, um, you can fill books with what has been developed since. Um, and so I think that that's where we can see these, um, a I options of really figuring out what's best for people, at least from a standard of care standpoint. And then the humanistic aspect of medicine will then be figuring out how to apply some of these things. Just because as we were talking about earlier in the rural setting in the nonspecialist setting, you know, keeping up to date with all of the latest clinical trial data and even how to read your National Comprehensive Cancer Network Guidelines and put a patient into the right algorithm is very difficult. And once you've got them into the right algorithm. A and you've, you know, figured out which of the 20 algorithms to follow. Um you now have four or five or eight drug options. Um uh you know, and some of them may be drug options uh with or without radiation added to it or, you know, so, so it's very difficult as a nonspecialist that might see a few cases of advanced prostate cancer here to figure out how to properly um figure out the best options for clinical trial and standard of care for a particular patient. But I think this is actually a very easy A I task. Um, now a lot of the commercially available A is that you can go on when you go and check GPT. I'm not gonna give you these medical answers yet. Um, because they're kinda told not to or they haven't been fed the right data to be able to do this, but the capabilities are clearly there. Um And in some of the custom A I work that I've seen, um, it, it's, it's certainly a very feasible thing to say. This is a patient's chart. These are the patient's standard of care options. Um And I think that once you get down to having access to that easy knowledge, you can then figure out, you know, what is, is within their goals and their interests and what they would like for their day to day life. And there's probably the potential for A I to help there too in that, you know, you could put some of these details in and understand how the treatments can affect that particular aspect of things, which doesn't then require the same level of expertise on the part of the clinician, which again, um if we're talking about delivering care for the most common cancer in men, um across a vast, um you know, geographic area, you're gonna have to have the nonspecialist oncologist, treating prostate cancer. It can't be that only prostate cancer oncologist, treat prostate cancer because it just isn't feasible. And so that's where, you know, some sort of assistance could really make it much more practical. And I think that making it much more practical is going to make it much better for patients. I think you've stimulated the future debate in uh advanced prostate cancer. And it's, it's really great to begin to touch on where we're gonna go with A I and, and how that's gonna change all of our lives. Um uh So really great to kind of see another potential application of it. Doctor Da Thank you so much for your time today and it's been great to kind of discuss with you how we begin to practically implement some of the latest uh research. We're, we're really grateful.