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I'm really excited to be joined here with Doctor Andy Lase and we're gonna be talking about advanced prostate cancer in the context of multidisciplinary teams. Um Doctor Lasse, thank you so much for, for joining us and I'm really looking forward to this discussion. Yeah, happy to have the opportunity to speak with you all today. Uh So at the start of these sessions, we like to uh put everything that we're doing in the context of a patient. And what what we've done is we've written a little er patient vignette which will help to frame the conversation we're about to have so that we are always bringing it back to the context of a patient. And the little vignette is, is this John, a 68 year old retired engineer was diagnosed with advanced prostate cancer after after experiencing persistent lower back pain and fatigue upon receiving his diagnosis at a community hospital. John and his family were understandably overwhelmed by the complexity of the treatment options and the daunting path ahead. So recognizing the necessity of a comprehensive approach, John's primary oncologist referred him to a multidisciplinary team at a larger specialized cancer treatment center. It MDT comprised experts including oncologists, radiologists, pathologists, urologists, palliative care specialists. And the team faced several challenges, complex treatment decisions, resource limitations at the community Hospital and ensuring John's quality of life throughout the process. So as we, as we delve into this discussion about the MDT, we want to keep the patient who faces that type of scenario at the front of our minds because that's the most important thing that uh that we're all dealing with. So uh in saying that doctor Lati, we're really um excited to kind of chat to you about um your experience and your approach in this area. I wanted to ask, can you elaborate on um the relationship with patients? Can you elaborate on how this translates into fostering effective collaboration within a multidisciplinary team for advanced prostate cancer, particularly when there are complex treatment decisions to be made. So, uh yeah, I'm, I'm very happy that you framed the discussion um as such, you know, patients really are at the center of what we do as healthcare providers and approaching problems and you know, formulating um strategies we really need to be mindful of the fact that that, that, you know, the patient is at the center. So when I meet with patients, I think the biggest approach and the most important um the function I serve is to be an educator and be an advocate and as you said, cancer in general, um prostate cancer probably even more. So, um we really need to leverage the expertise and the specialization of various people, whether it be surgeons, radiation, doctors, medical oncologists, and oncologist, a sound communication and um coordination of these services is is is very important to um excellent patient care. So first and foremost, II inform patients as to my role amongst the greater multi disciplinary team as a medical oncologist, I also informed them that I will serve as their um care coordinator and as their center point of contact to help guide them amongst the services and the teams that they need to gain access to a lot of what I do has to do. Um revolves around providing education and comfort and a realization that that patients have a partner in um what, you know, the care and the journey that they're about to embark upon and um you know, serving as a compassionate and um you know, willing, a willing aid in that process is what I pride myself in. And um how would I approach my, my patients? Really interesting and, and, and it is all about that patient and, and collaboration amongst amongst a team, you kind of touched on the strength of some um some different health care settings. II wonder whether you might be able to chat about how tertiary or quaternary level centers best collaborate with community hospitals to begin to optimize the treatment plans for patients with advanced prostate cancer, especially considering resource limitations and all of the all of the challenges. Yeah, it's, it's a, it's a very challenging um topic. So, uh you know, I have the, you know, the, the benefit of practicing at a tertiary center. And um my expertise is in prostate cancer and that's the field in which I II deal with day in and day out. And I have the luxury of being able to, you know, dedicate my time, my effort and my educational and, and research endeavors into that one focused area. I am in awe of community oncologists and community subspecialists understanding their responsibilities and their focus is more broad and diverse. And the challenge in that capacity is to be an expert as much as one can be in multiple things. And that's a very big ask and a and a very um tall order that uh it is is is asked upon those working in the community. Similarly, um access to specialized uh treatments may be more limited, which is understandable, understanding the facts. Um Community centers are responsible for such a wide array of disease types and scenarios. So, orchestrating a si a situation through which uh a patient can benefit from the expertise and the focus of a tertiary center while being able to receive care um through i in through the um execution of a local team and the convenience that that provides is really the best of both worlds. So, you know, at our center, we pride ourselves in our ability to engage and interact with our community liaisons. Um And that's a, a first and foremost, a recognition of the skill sets and the benefits um uh provided at each center. So, m my approach is to again provide um you know, expert counseling and guidance for, for um folks that are working within the community and, and allowing for an, an, an understanding of the resources they have and the comfort level through which they're able to execute care. So the best approach is to be in uh avid communicator and one that's able to be um y you know, malleable and uh adaptable to various circumstances because no one situation is the same and um you know, doing your best to accommodate that diversity is the best strategy. In my opinion, I wanna dive into a little bit of the, the science of it. OK. Doctor Li. So emerging therapies have pretty intricate inclusion and exclusion criteria um that poses a challenge for MDT S. But um uh what do we need to do? What, what, what uh what can a community team tee up so that when patients are um being seen by you, that they are identified in the most efficient way as to whether they are suitable for participation in some of the most promising clinical trials, what, what that do you need? Maybe touch on some of those inclusion exclusion criteria so that we can begin to uh tee tee patients up. So that, so that they get decisions as, as fast as they possibly can. So it's a great question. And I think um the best counselor I can provide is to be comprehensive in the workup and uh fastidious in trying to follow guidelines for the best practice and care um in the vein of pro you know, in, in the world of prostate cancer um following the NCCN. So National Cancer Consortium Network Guidelines or the American Society of Clinical Oncology um Guidelines uh is a good place to start and information pertained within, you know, that guideline infrastructures that will um you know, uh allow for about 90% of the information necessary to evaluate for clinical trials a little more granularly. We're looking to ensure that patients have a tissue diagnosis, which is a necessity for most clinical trials. So a biopsy will have been performed and then relatively up to date imaging in the world of prostate cancer, CT Scan and bone scan still dominate the research landscape as our primary tools for uh imaging. Although we are entering an era of ps ma pet scans. So prostate specific membrane antigen, pet scans, which are more so being incorporated in uh disease classification. So, beyond tissue and imaging and understanding of a patient's fitness level is really important. Um One of the more common exclusion criteria in clinical trials is if patients aren't healthy enough to um you know, meet candidacy for the study and generally, we will determine that based on performance status or whether cards performance status or uh ec performance status. Uh So, having an understanding of how fit the patient is, is important. Um lastly, um a very solid understanding of, of how patients have been cared for in the past is really critical to determine whether they're a candidate for a select study. It's common for certain treatments um as prior therapies to be included within inclusion and exclusion criteria and having a detailed map of the, the the care journey and treatment history is very important. You've touched on something though, that's quite important that um not all patients are suitable for. Um uh either latest therapy or even latest clinical trials. Uh and palliative care is often underutilized. Um Do you share your insights a little bit on how MDT S can better integrate palliative care specialists from the outset to improve not only quality of life but potentially patient tolerance and treatment adherence for advanced prostate cancer. It's a, it's a really important topic um in the in prostate cancer. Even in the advanced and metastatic setting, patients live typically for many years with their disease. The latest evidence suggests that newly diagnosed metastatic prostate cancer uh demonstrates a media and survival time of, of, of close to seven years and for the duration of that time, patients are often on treatments that poses side effects um that can potentially detract from quality of life. So both of the situation where patients are healthy at the offset uh onset or coming in a little sicker utilization of palliative care and support services to best address symptoms and side effects is critical. There, there have been several studies published to suggest that the earlier implementation of palliative services um best benefits patients in terms of quality of life. Um and there is some data to suggest that maybe your outcomes can, it can improve um through, you know, expanded access to drugs, better tolerance, et cetera. So I do think that the incorporation of palliative care um early is, is, is a very important element, whether that's done at a, at a um tertiary care center or within a community palliative care group. Um I think it is, is on a case by case basis. Um but really addressing the symptomatic needs of patients aggressively is uh you know, critical and that can be done through, you know, uh uh uh in the care of a, a medical oncologist, but in an ideal world, partnering with a palliative care expert um where this is their primary focus is um what should be done, you know, in the vast majority of cases. So, Lati thank you so much for uh joining us and we really appreciate your time. Thank you very much and I'm just gonna pause for a second. I'm gonna keep the recording. Thank you. Is that OK? And don't be afraid to get into some of the science as well. And it's like kind of relatively high level questions, but um we will, we will have oncologists joining us. We've got um really broad audience. So there are some conditions as well. So um feel free to dive into, to some of the science as well. You're the expert on this space, not, not me. So, um so I need to kind of follow your lead a little bit on that, but um but yeah, really good and uh really, really nice natural conversation. So um so that's great. Um OK. Are you happy to dive straight in? So that's, that's fine. I think this one, I can be more data centered. Uh Sure, some of those questions are hard with like the D MT and they're there but I can't say data to support them. But right. So questions I get it. They're really so questions. So um but yeah, I've, and I've tweaked this one a little bit so that we can kind of almost gee geek out a little bit on uh on some of the data stuff. So that's good. Um All right. Nice. Uh OK. Um So I'm really excited to have er Doctor Lati joining us again uh to talk about advanced prostate cancer and this time talking about evaluating emerging therapies in advanced prostate cancer. As you know, we like to frame our conversations around a patient so that we can take everything that we're saying back to the context of the clinic and more importantly, the patient's life. So what we've got is a little fictional vignette that we've written and we hope to use that to frame our conversation in your mind about how this applies to patients. And the vignette is this mark, a 70 year old retired teacher was diagnosed with advanced prostate cancer. Initially, he responded well to standard treatments but his cancer eventually progressed, necessitating consideration of new therapeutic options. Mark's case exemplifies the challenges and opportunities in staying current with evolving clinical trials, integrating emerging therapies and balancing cost with clinical benefit to provide Mark with the best possible care. His medical team decided to navigate the complexities of new treatment protocols, assessing the risks and benefits of novel therapies like parp inhibitors and incorporating innovative remote monitoring and exercise interventions to enhance treatment outcomes and patient compliance. So, as we explore Mark's journey, uh it's really important that we begin to think about uh the latest clinical data and that's what our conversation is gonna be about this evening. So, clinical trials are constantly evolving doctor from the latest clinical trial results in advanced prostate cancer. What are the key changes and updates in the evidence that colleagues need to be aware of in terms of changes in accepted clinical practice? Mhm So um thank you so much. Um I am, you know, happy to speak on this topic and it's a very exciting one and this is a a very uh unique time period in uh prostate cancer evolution. Um in that we have new treatment modalities emerging, what seems like yearly and new treatment strategies that are changing the standard of care, um you know, periodically uh and, and to a degree that the, the standards are shifting, um you know, very, very frequently and, and requiring us to uh maintain a very um firm understanding of, of the literature and that evolving data. So I'll start off um you know, taking a step back from Mark's circumstance, uh you know, with him presenting as a um castration resistant prostate cancer through through which that has progressed on first line therapy. A lot of what is done in the castration resistance setting is contingent upon how we manage castration sensitive prostate cancer, which you know, is, is defined essentially as treatment naive metastatic prostate cancer that which responds to some of our hormonally based therapies in the metastatic castration sensitive setting. There have been two landmark clinical trials published over the last 2 to 3 years evaluating the value of triple therapy. So triple therapy referring to a DT androgen deprivation therapy in combination with um an oral novel hormonal therapy, specifically abiraterone or dalamide. And, and then in combination with DOCEtaxel chemotherapy. So these two clinical trials, one was called the A SN study and the other one was called the P three trial. We randomizing patients to receive uh the three drug combination or a two drug combination inclusive of of A DT with chemotherapy. The only difference between the two clinical trials was the oral hormonal therapy agent that was selective in P three, it was uh abiraterone and ariens. It was dalamide. And essentially these two studies have um been reported in support that the use of a triple therapy strategy is superior to that of a double edge strategy including chemotherapy and injectable GNR agist antagonist, uh hormone therapy. The benefits have been demonstrated with respect to overall survival and progression free survival. And um triple therapy has emerged as a new option for the management of metastatic castration, sensitive prostate cancer. Now, an important topic to um pay attention to is the fact that both of these studies were performed using chemotherapy and A DT as the comparator arm. No studies to date have demonstrated the superiority of a triple therapy regimen compared to an injectable hormonal therapy, GNRH agonist antagonist and one of the novel oral hormonal therapies. So we are left with somewhat of a dilemma understanding that triple therapy is not yet um the proven standard of care for all patients given this comparative um design. So, I it's a nuanced decision through which, you know, medical oncologist needs to navigate. Um The data currently supports the higher volume or higher risk prostate cancers and particularly those involving visceral organ metastasis, probably benefit from the triple therapy strategy the most. But there still should be a, you know, significant number of patients that are receiving double it hormonal therapy, GNR H agonist with one of the horrible therapies. So it, it's a challenge that we are up against, but this late breaking um evidence does support triple therapy is a good option for many patients. Um So I'll pause here for a second to see if there's questions regarding this clinical trial. I guess what, what I'd love to um dive into doctor LTI is the kind of identified uh risks and side effects, I guess with some of the more promising new therapy. So thinking about ARP inhibitors, for instance, um what can you can you maybe elaborate a little bit on that? Yeah, of course. And um you know, more broadly speaks to some of the newer agents that have been approved in castration resistant prostate cancer. So, um you know, uh most patients having received hormonal therapy and now often chemotherapy in the castration sensitive setting, we are in dire need of newer and unique treatments for later line castration resistant prostate cancer. Um You know, as mentioned, parp inhibitors have emerged as a uh viable option for patients that have candidate genetic mutations. Uh in particular DNA damage repair mutations such as BRCA 12 and ATM. So Olaparib and um uh Luca and most recently, Tzar are parp inhibitors that have been approved in the castration resistant prostate cancer setting. Again, for patients with these candidate DNA damage repair mutations, this was based upon several clinical trials. Um and Um Even more recently, we are now given the option of combining parp inhibitors with novel hormonal therapies, specifically enzalutamide with Talib and um uh olaparib with abiraterone. The application of this combination strategy is again a little more tricky because the studies were done at inclusive only of patients that had never received an oral hormonal therapy. And as I mentioned, most patients are now currently receiving an oral hormonal therapy in the castration since you've said it. So it is a little bit of AAA data challenge for selection of the uh single uh single therapy option versus this double therapy option. Uh But we are gaining more insight day to day to which strategy makes sense. You know, to go back to the initial question and answer side effect are really a critical concern. Um As we talk about any new novel um kind of treatment um in prostate cancer parp inhibitors have several AKI class side effects including tiredness. Uh In addition to uh low blood cell counts, we can also see issues with uh altered taste and diarrhea. Um anemia becomes a critical issue. Um Also un under the understanding that many patients with prostate cancer have preexisting anemia. And looking at um you know, the registry trial for Talazoparib and Enzalutamide. In particular, many patients do require blood transfusions. So navigating these side effects requires, you know, close attention to detail, um frequent blood checks and touch points with patients to assess for symptoms but in general, they're pretty manageable. Like the, the, the field of precision medicine is like rapidly advancing. And um I'd love to hear your thoughts on um how you envision the role of genetic and molecular profiling uh changing in, in, in the guidance and selection of emerging therapies so that we can begin to increase the way in which we tailor our treatments for individual patients with advanced prostate cancer. Mhm. No, it's a really excellent question and that can you know, address it in, in several themes. So when one conventionally thinks of um uh personalized medicine in the in the cancer world, genetic testing is is front of mind. So we've already alluded to the fact that we have one genetically um guided medication option through parp inhibitors. Um There are others that are currently under development. Um One of which is uh immunotherapy. So specifically keytruda pembrolizumab has been approved for essentially all solid tumors that demonstrate microsatellite instability, which is a a feature that we will see on next generation sequencing. Uh Additionally, high tumor mutational burden on genetic testing can convey candidacy for pembrolizumab. Now, this is an important criteria. Understanding that immunotherapy for most men with, with advanced prostate cancer has not demonstrated benefit. But with these select mutations, we are finding candidates for the treatment to receive. Um uh you know, both palliative and um survival advantages. Um There are other mutations that are currently being considered. Uh There is a splice variant known as A RV seven, which is appreciated to be uh one of the trial mutations for hormone therapy resistance clinical studies are underway to help guide both existing and novel hormonal therapies using a RV seven as a um AAA directory test um for the use or um uh omission of these treatments. We're also entering an era beyond genetic testing through which we're able to look for uh candidate proteins in the prostate cancer that allow for um your molecular targeting pluvicto or lutetium 177. PS MA has recently been approved for the the treatment of advanced prostate cancer. After patients receive chemotherapy and use of this drug is guided by a compendium pet scan. Diagnostic patients undergo PS ma pet scan which labels um prostate cancer for the candidate drug target prostate specific membrane antigen. And we're rationally selecting patients that have high expression of this target uh to receive the drug. We're poised to enter an era in which you know, histologic and and pet modalities are best selecting patients for various treatments. Um There are explanation uh ee you know, exploratory clinical trials, looking at antibody drug conjugates and novel radio ligans directed towards PSN A for patients that have neuroendocrine type prostate cancers, which is unfortunately a an a not uncommon evolution of the cancer. Uh There is a tracer called DLL three for which um pet scans are, are under development and novel drugs including Bispecific antibodies and potentially radio likings. So, you know, as mentioned, personalized care of of advanced prostate cancer patients are really um is really developing well um and drawing everything back to, you know, the, you know, the initially um mentioned this patient um who is in dire need of newer treatments. II suspect that these tools um are on the horizon um to help benefit patients like him and others. I really love bringing you back to that, that patient, right? And uh and as you said, it, it's quite a promising time for uh for patients with advanced prostate cancer like Mark and, and that's what this is all about. So, uh we're really grateful um Doctor Li for, for your time today and uh thanks for giving us such a comprehensive um update on some of the latest evidence and accepted practice. Thank you, my pleasure. Thank you very much.