Charles Ryan: Hello and welcome. Today we're going to talk about the Coffey-Holden meeting, which is really one of the most special events that's held by the Prostate Cancer Foundation every year. And as you'll see in here, it's an amazing opportunity for young scientists to get engaged with their colleagues, get mentorship, and share very early results. The three organizers of the meeting are joining me today. The first is Howard Soule, who's the Chief Science Officer of the Prostate Cancer Foundation. Second is Ken Pienta, who is a Professor of Urology and Oncology at Johns Hopkins University, and Andrea Miyahira, who is the senior director for global research at the Prostate Cancer Foundation. Thanks to all three of you for joining us. What a great event that you've put on every year, and I look forward to hearing more about it.

Ken, I'm going to start with you. Tell us a little bit about the origins of this meeting and why it's called Coffey-Holden.

Kenneth Pienta: Thanks, Chuck. It's always exciting for me to talk about this subject. The origins run back to the 1980s when there was still an organ systems branch for the National Cancer Institutes and Andrew Chiarodo, who ran the organ systems branch, got together with Don Coffey, the former director of research here at the Brady Urological Institute, and really the father of prostate cancer research in this country. I think I can say that unabashedly. And they put together this idea that once a year they would go to Prouts Neck, Maine and have a meeting of about 75 people that would address a major question in prostate cancer that they chose.

And they put together those 75 people. About 25 of them would be young investigators, young folks in the field, 25 folks that were experts, and then they would have a collection of other folks who might be from outside of prostate cancer, but were experts around that question. And they would have a think tank for basically three days out in Prouts Neck, middle of nowhere. Everybody had to come for the whole time. And it was a great camaraderie-building exercise because we all had meals together, we launched rockets together, had morning prayer services together. It was just an amazing conference.

And they also, Don, and made the rule that basically every time they had this at least half the people had to turn over, had to be new. So there was always this idea that you would be getting new ideas. We didn't want to form a club, so to speak. But those were the Prouts Neck meetings.

Those went away when the organ system branch of the NCI went away, as well as funding for meetings went away, and there was no way to have them anymore. And it was a great loss to the field. So I think we decided to try to bring those back. I think Howard can talk about that a little bit. But we really wanted, in bringing those ideas back, we really wanted to name this meeting going forward after really two giants in the field, Don Coffey on the science side, and Skip Holden as the clinical urologist who's driven so much thinking also. So that's the history, and I'm just very excited that we've continued that in this new format.

Charles Ryan: It is a really interesting history and it's a really important format. And so one of the things that sets this meeting aside is this is not something that people put on their calendar every year to go and to get the latest updates. It's really a think tank. A couple of words you used there, think tank, you described recycling of individuals who are there, a way to keep the ideas fresh and moving forward. So, Howard, you might want to comment on this, and then we'll talk about the 2022 meeting, which has just been published. But you might want to comment on how one gets invited to become part of the Coffey-Holden meeting.

Howard Soule: Thanks, Chuck. Well, I have to give great praise to Ken Pienta, who called me in 2012 and said, "We used to do this Prouts Neck conference, which predated me in this field, and I'd like to do it again, and we'd like to do it with PCF." So we did in 2013, we had our first, what we called, still called Prouts Neck, but we actually convened in Incline Village, Nevada. And to kept the tenents of Don, who we affectionately called the Yoda of prostate cancer research. We've maintained a fresh outlook on the science. People should recognize that no talk is longer than 10 minutes, followed by 20 minutes of questions. So the immersive, scientific event that Don Coffey started back in the mid 1980s in Prouts Neck has been maintained throughout.

Charles Ryan: Great. And, Andrea, so we're going to shift to you now. Talk a little bit about the past year's meeting. You are the first author of this paper that was published in The Prostate in November of 2022 that highlights the discussion items from the meeting. Tell us a little bit about what were the highlights.

Andrea Miyahira: Sure, Chuck. Happy to. So our paper titled Exploring New Frontiers in Prostate Cancer Research, Report from the 2022 Coffey-Holden Prostate Cancer Academy Meeting, was published in the journal The Prostate Online in November, 2022. This was a summary report put out by the organizing committee to disseminate the science that we discussed at the meeting.

The report starts out by reviewing the history, format, and purpose of this conference as Ken and Howard just described. And after that, we provide a pretty in-depth review of the presentations from the meeting. At the top with the focus on prostate cancer health disparities. And people of African ancestry in particular have a significantly higher risk for prostate cancer incidents and mortality compared with people of European ancestry. So to advance health equity, we do need to better understand the socioeconomic and biological determinants of prostate cancer disparities and achieve better representation of minorities in research.

So in this report, we detail studies on key contributors and determinants of prostate cancer disparities as well as possible solutions. For instance, we discussed how socioeconomic inequities resulting from structural racism appear to be key drivers in prostate cancer health disparities and strategies for studying these. We also discussed studies on possible biological contributors, including genomic ancestry and immune and metabolic factors. We highlighted strategies to advance health equity and address social and structural inequities, including novel healthcare system approaches, improving diversity in clinical trials, developing trust between patients and doctors, and developing racially and ethnically diverse preclinical prostate cancer models, which are currently really limited in our field.

A second major topic area was on the responsible use of real world data to accelerate research and trials. So there are many large data sets from clinical trials including real world data sets, some of which include biorepositories that are being used for biomarker discovery, discover possible surrogate clinical trial endpoints, and novel usage such as virtual clinical trial arms are to stimulate clinical trials and make go/no-go decisions in clinical development. So we discussed the strengths and caveats for using each of these approaches.

The application of artificial intelligence and biomarker approaches in radiology, pathology, and genomics was another focus area. AI approaches discussed including using AI to improve the accuracy of multi-parametric MRI and prostate cancer detection and treatment planning. Applications in pathology to better predict outcomes such as metastasis and the creation of AI tools that are combining clinical and pathology data to improve diagnosis and clinical decision making.

We also went deep into prostate cancer biology in several topic areas. One of those was on DNA repair defects, which are common genomic alterations that are seen particularly in advanced prostate cancer, and importantly they serve as biomarkers for PARP inhibitor therapy of which there are already two approved therapies. Unfortunately, there is variability in response, it is not well understood, and that may be due to differences in the specific gene alteration, or the chosen PARP inhibitor, or other unknown mechanisms. And so we discussed new biomarker approaches for identifying patients most likely to respond to PARP inhibitors as well as additional biology around DNA repair defects.

The androgen receptor, or AR, remains the primary therapeutic target in prostate cancer. However, as patients progress, AR ulcerations and dependence of tumors on the AR pathway becomes more heterogeneous. So we had talks on the 3D structure of AR, which will allow us to better understand the molecular biology of AR and design improved targeting agents. AR does not work alone, and so we have discussed approaches for targeting AR co-factors and regulators such as the SWI/SNF complex and the role of epigenetic alterations in AR expression heterogeneity.

And then finally, PSMA theranostics have recently been one of the most exciting new areas in the field with the recent approvals of several PSMA PET imaging agents, and the PSMA radionuclide therapy, Lutetium-PSMA-617. Unfortunately, resistance to PSMA-targeted molecular radiotherapy is inevitable, and studies to understand the mechanisms of resistance were a point of discussion.

We also discussed the role of FTT PET, particularly for its uses of potential imaging agent in advanced prostate cancer, and as a treatment selection biomarker for PSMA-targeted therapy and AR-targeted therapy. In addition, we had theranostics experts from thyroid, neuroendocrine cancer, lymphoma, and other malignancies there to discuss the progress in their fields and how to apply those lessons to prostate cancer.

Charles Ryan: So yes, a broad diversity of topics ranging from structural components of the androgen receptor to disparities in the care delivery. What are some of the newer concepts that you're seeing emerge in the context of this meeting over time?

Andrea Miyahira: Well, I think bringing in different new, young investigators each year shows us where the field is evolving, really at the leading edge. And so it's exciting to see, for instance, nuclear theranostics. Where are we going after PSMA? Where are we going after Lutetium? And so some of the new radioligands, and some of the new targets, and some of the new agents that are being developed, it's really an exciting area. And also there's been really a focus on disparities, at this last meeting in particular, and especially after COVID. People really see that as a problem, and how to address that in their research specifically, I think, was another big topic that was focused on this last year.

Charles Ryan: Terrific. So let me focus a little bit on the article that's just been published in The Prostate, Andrea. Could you walk us through the components of this, and what might readers want to pick up from this publication?

Andrea Miyahira: Right. So the article really goes through the sessions, and the speakers, and just highlights the topics that each speaker talked about. And so there's a big section that focuses on prostate cancer disparities and diversity. How can we better understand biology and social determinants to advance healthcare and outcomes? For instance, bridging the gap between different biologic individual and macro environmental factors, strategies to increase clinical trial equity, as well as strategies to increase representation in research samples. So there are a number of topics, also different biologies that have been researched, as well as studies into the biology that underlies some of the racial and ethnic disparities that we see in prostate cancer.

In addition to that, we had a session focusing on 21st century-responsible speeding of new treatment to the patients. This is focused on different types of surrogate endpoints, and how do we use real world data. For instance, there are many large biorepositories that are available, and how can we really use this data to understand which treatments are working, which biomarkers are working, and which populations should be treated with which treatments? And for instance, the VA has a really large data set that a lot of studies are using to really understand how treatments are being applied and how they're working in different populations. And that is a good data set to use to look at different patient types. It's well represented with African American and other minority populations.

Another session focused on AI and biomarkers in prostate cancer. Where are we going with that? Particularly, radiology and pathology are two of the leading fields where AI is being implemented. What does that mean for research and what does that mean for people that are in that field? How can we use this to really better understand biology and develop better biomarkers for patients? Another focus of the paper was studies looking at single cell analysis to identify prostate cancer heterogeneity and identifying new therapeutic targets. These as well as how to identify homologous combination disparate defects in patients with prostate cancer.

Another session focused on how to target inhibit AR. So we had a talk on AR structure. There are also talks on targeting the SWI/SNF ATPases and enhancer addicted prostate cancer. And so where can we really leverage the data, the new data that's coming out, to target AR, target other factors that are involved with AR? And then which populations or which patients would this even be effective in? We know that CRPC is driven by AR in most patients, but not always, and this is changing. And so how do we understand which patients, and also the heterogeneity of prostate cancer?

Another major topic area was immunotherapy and where are we going with that. Immunotherapy has not yet been highly successful in prostate cancer, and so we consistently see new approaches to try to turn the prostate cancer microenvironment from cold to hot. And so some of the topics that we talked about during the meeting were using radiotherapy to enhance abscopal effects. Will that even work? And how do we get it to work? The role of the myeloid compartment in suppressing prostate cancer immune responses.

And then we also had a major session focused on nuclear theranostics. So we had speakers coming in from other fields, including neuroendocrine cancers and thyroid cancers, lymphoma, and other malignancies, where some of these therapies were developed early on. And how can we learn from those fields and really forward the field in prostate cancer?

Charles Ryan: Well, that's a pretty comprehensive review of all the topics discussed, and really interesting and diverse biological and even societal topics that impact prostate cancer.

Howard, I want you to comment a little bit about the unique structure of how people give a talk. It's a relatively short talk followed by literally a long line of questioners, and that's been one of the real points of pride to engage in dialogue. And that's one of the things that makes us different from other meetings. Tell us a little bit about how you structure that.

Howard Soule: Thank you, Chuck. Great question. This is one of the most important events that our science team puts on each year. It is entirely unique in that we create a safe environment for young investigators to present unpublished data. That is the credo of PCF, and this meeting exemplifies it. So we consult the presenters that you do not have to any background slides, you don't have to give what Andrea Miyahira and I call the ditto slide, which is number of cases per year, number of deaths in the United States. That's not what you have to do here. You have 10 minutes to present your thesis, and as the clock winds down ... And Dr. Pienta keeps track of the time. He's tough, he's a tough moderator. We see a line of people begin to form in back of the two microphones in the aisles of the seating area of the event. And the 10-minute talk is followed by 20 minutes of really intense questions, and gloves off.

These people know that if they stand even a 10% chance of coming back a second time to a Coffey-Holden meeting, they need to be prolifically involved with the conference. They need to ask questions, they need to engage speakers, at all levels of their career. So that's really what sets this meeting apart from the endless number of scientific conferences, medical conferences, biomedical research conferences that people can attend every year. We are all about immersion. And every one of the topics that Andrea just reviewed is organically a life of its own. And it's just so much ... To be able to have ... It's a privilege to be able to have four days of just immersion in people in their science. That's what sets it apart.

Charles Ryan: You also used some really key words there, such as a safe space. It's spirited conversation and discussion. It's not confrontational in a way where young scientists are felt to feel inferior or belittled. And I think you both, all of you, deserve congratulations for helping to make that environment cultivated in such a way.

Ken, perhaps you want to give us a comment on that aspect of the spirited conversation without necessarily ad hominem confrontation that sometimes happens at scientific meetings.

Kenneth Pienta: Yeah. I think that Howard got exactly right. This is a safe, but not only safe, but fun activity where we go in to challenge each other. And there's almost a little competition of who can ask the most questions. Literally we have 400 questions asked over the space of two and a half days. We've never ended a 20-minute question period early because there were no questions. It's an unbelievable phenomenon to watch this happen. And that free-flowing intellectual event leads to conversations, collaborations. I can't think of how many grants got started based on conversations from a question that started at Coffey-Holden, to a conversation at dinner, to all of a sudden we're seeing a Challenge Award. It's Amazing.

Charles Ryan: It should be stated that we all stay at the same facility. All the meals are shared. You have to exercise together sometimes. No, you don't have to, but there's a strong encouragement for group exercise. Again, speaking to the nature of the community that's being built.

In contrast to the scientific retreat where we do engage with many corporate partners and sponsors, the Coffey-Holden meeting is funded entirely through our philanthropic efforts. Howard, I wonder if you could comment on that.

Howard Soule: All right, well, you're absolutely correct. The reason that we don't seek corporate sponsorship for this event is based on a limited number of seats that we have. It would be great to have drug company scientists there, and we welcome those people to our scientific retreat every October in Carlsbad, California. But this meeting is smaller, more compact, and it just doesn't work to have a lot of industry invitees present at the conference.

Which makes it difficult to sustain. We funded right now out of general contributions to the foundation, but we sure would like to see an individual or a group of individuals step up and become donors to this really important event for us. This is not just to build careers or to enrich people's science knowledge, which it does, and it does it very well and in very unique ways. But this is a meeting that PCF uses to put two fingers on the pulse of what's going on in the field. Who are the new people that we should know? What are the new ideas that we should address to bring an end to this disease? So having a donor or a group of donors from the public would be extremely ideal.

Charles Ryan: Howard, let's talk about the future moving forward, your hopes for this. Continue it? Grow it? Keep it as exactly how it is? What do you see coming?

Howard Soule: Yeah, thank you for that question, Chuck. Come hell or high water, we want to continue this meeting. We've done this through pandemics in a virtual setting. We thought about actually doing two of these a year. That's how valuable we believe this conference actually is. To even broaden further the topics that we have and to engage two cohorts of young people instead of just one. So we see a bright future with sponsorship. It always takes some money to put these on, but this meeting has just become a part of our DNA, and we can't be successful without it.

Kenneth Pienta: I have two comments. One of the issues that we have with the meeting as we try to contain expenses is that we've made this a US-only invite meeting, which of course works, but it also, sometimes we can't invite some folks that we really would love to have just because of the cost of bringing them from overseas. And that's why we talked about having a second meeting, even in Europe, because there's so many great investigators across the pond, so to speak. So that's one of the issues of why we need some sponsorship, quite frankly.

I think one of the great strengths of the whole Coffey-Holden experience is that we really emphasize the interdisciplinary science that we all celebrate and use. This is not a siloed meeting. If you look at who we invite, it's across a broad spectrum of expertise, both at the level of the young investigator as well as the seasoned investigator, including folks from outside the field. And that's how discovery happens. That's how good science happens. And then this era of team science and interdisciplinary team science, convergent science, I dare say mayonnaise science, the Coffey-Holden is teaching these young people the importance of that and how to do it.

Charles Ryan: Andrea, can you comment a little bit on the multidisciplinary nature of the author list on this paper?

Andrea Miyahira: Sorry. Yeah, that's one of the things that we consider each year is how to create a committee that's actually multidisciplinary. We usually have representatives from basic science, medical oncology, and then other fields including radiation oncology, urology, nuclear medicine, etc. We try to make sure that our committee is multidisciplinary so that our agenda will also reflect that.