Luminaries in Prostate Cancer: How the Past Informs our Future
PANEL DISCUSSION: Luminaries in Prostate Cancer: How the Past Informs our Future
Moderator: Phillip Koo (Prostate Cancer Foundation)
Panelists:
Maha Hussain (Northwestern University)
Oliver Sartor (Tulane University)
Cora Sternberg (Weill Cornell Medicine; New York-Presbyterian)
- Look back on advanced prostate cancer and where we are headed from here
- Panel plus Jum Hu (Weill Cornell Medicine) – Future opportunities in urologic oncology
- Panel plus Neha Vapiwala (University of Pennsylvania) – Future opportunities in radiation oncology
- Panel plus Emmanuel Antonarakis (University of Minnesota) – Future opportunities in medical oncology
- Panel plus Michael Hofman (Peter MacCallum Cancer Centre) – Future opportunities in nuclear medicine
- Open Q&A
View the Transcript Below:
Luminaries in Prostate Cancer: How the Past Informs Our Future
Phillip Koo, MD [00:00:05] Good afternoon. So, thank you all for returning. Before I get started, I wanted to thank Howard, Andrea, and the entire PCF staff. Putting together this retreat is a colossal task. But what’s even more challenging, which they really do a wonderful job on, is maintaining that science program throughout the year and really building that community, which I think we all agree makes a huge difference. So, we wrapped up a pretty amazing morning, and we learned a lot about some of the history regarding PCF, regarding various opportunities. It was nice to hear Dr. Belldegrun’s story, Dr. Hussain’s story. So many different stories that should hopefully inspire us and give us a lot of optimism about what the future holds. So, we have three goals for this one-hour session. Number one, really helping to define what the unmet needs are. Clearly, we’ve made a lot of advances, but what are some of the unmet needs? And for that, we have a panel of three right now. We have Dr. Hussain, Dr. Sternberg, and Dr. Sartor. Maha made a comment last night that this was the gray hair panel. I don’t see many gray hairs. In fact, I think I have more gray hairs than all of them combined. But yeah, very much looking forward to that.
Maha Hussain, MD, FACP, FASCO [00:01:22] It’s the wisdom related.
Phillip Koo, MD [00:01:23] Exactly, there’s a wealth of wisdom and we’re gonna tap into that today. Number two, Dr. Belldegrun said it, we are gonna define the future, the collective future. So rather than following the future we have the best of the best minds here so hopefully we could have open discussions and help decide what the future’s gonna look like for our prostate cancer patients. And number three, I hope you all walk away motivated and inspired about what we can do together. And one thing I can attest to is that everyone on this panel is very approachable. They’re so motivated to help. If any of you feel intimidated, which I remember early in my career, I felt intimidated to approach any one of them, but please approach them, talk to them, get to know them. And I think you’ll build these long-lasting relationships and perhaps mentorships that can help you in your career, regardless of where you are on that journey. So, we’re gonna go ahead and get started. And first off, Maha, congratulations on your Lifetime Achievement Award. Very well deserved.
Maha Hussain, MD, FACP, FASCO [00:02:24] Thank you all. Thank you.
Phillip Koo, MD [00:02:27] So you sort of went through a lot of what happened in the prostate cancer space. To you, what are some of the gaps that still remain?
Maha Hussain, MD, FACP, FASCO [00:02:35] So I think there is the issue of what we have available, but there is everyday reality of access to care. And so, I will talk more about the medicine and biology, but I would say the hard part for me, and working in downtown Chicago, it’s a great area. When I see patients coming in, and this is a recurring theme from when I was also in Michigan, is the co-pay factor is a huge issue. So, you can come up with a greater treatment, but if patients can’t access it, it’s a big deal. Then those who are, let’s say Medicaid, it’s hard. Sometimes we go with compassionate use with pharma and they help with that. So, to me, I think if we wanna push something at the political level, I don’t mean like, but pushing in for advocacy for our patients, is access to care is gonna be the critical part. And then making sure that what we have available. In the sort of the major cities is also available in rural areas and smaller towns and things like that because that’s another issue that I see and this has been going on forever, it’s nothing new. However, when it comes to the medicine part and the science, I really think that it’s gonna be very critical to better understand the biology of the cancer, as I mentioned in my slide, as we’re moving all these treatments into the earlier phase of the disease. And earlier stages, the question comes up is, I know that we’re not curing patients yet. The question is gonna come up, what are the mechanisms of resistance? What are the progression mechanisms and things like that that would happen? Another thing that I would like to advocate for, and I’m hoping that maybe we can come up with a project that we can all work on. Several colleagues of mine here are involved in an abstract I just recently put, because all of a sudden, I’m beginning to see the last five years, or maybe four years, men who got doublet or triplet, more of the modern doublet and triplet, and then five minutes later, they developed disease progression in the visceral disease. And I usually biopsy it, and it turns out to be small cell. Or like an aggressive neuroendocrine variant that’s a small cell variant. And the question is biologically why this is happening, because I’ve never seen it before. So, there is a lot of things that I think we need to delve into. We’ve come a long way. I do think moving early treatment, the treatments, into the certain high-risk disease earlier on, if we can somehow have adjuvant trials designed to try to hopefully prevent relapse and metastatic disease, that would be another ideal situation.
Phillip Koo, MD [00:05:13] That’s great. You know, one thing I’ve always loved about Maha is she never is afraid to speak her mind. So, if you want to have follow-up discussions, find her afterwards and she’ll tell you the whole truth and nothing but the truth. So, we’re going to turn to Cora next, Cora from Weill Cornell. I’ve gotten to know Cora, wonderful person, clearly very, very successful career and part that early group of women GU oncologists. Cora is unique in the fact that she’s had so many leadership positions here in the United States and also outside the United States as well. So, what are your thoughts here from your lens?
Cora Sternberg, MD [00:05:48] From my lens, prostate cancer in the last 10 to 15, I’ve worked in Europe, I worked in the United States. I say in my career of at least 30 years taking care of patients with prostate cancer, we’ve made more remarkable achievements in the 10 to the 15 years than have been made in 50 years. I mean prostate cancer was considered just one disease, everybody got ADT, and then in 2004, miraculously, everybody got docetaxel. And what did we do? We did 10,000 patient trials with docetaxel plus drug A, B, C, D, whatever, off the shelf, not understanding that they were all negative trials, that prostate cancer is not just one disease. It’s many different diseases, and we need to understand the genetics, the genomics, the pathology of the different diseases. Now, we know about BRCA and HRR, and we can give olaparib. We know the MSI patients. We can give immunotherapy. We know about neuroendocrine differentiation. We need different treatment for those patients. And I think that with PSMA and PSMA imaging and theranostics, it’s another kind of imaging that is changing our field rapidly. So, one of the reasons I came to work in the United States is because I’m working in the Englander Institute of Precision Medicine. And we do genomics and genomic detailing, and I think what needs to be done is that all patients need to have a more precise diagnosis with precision medicine and genomics and to better understand what their tumor is, and to understand what kind of tumor they have, whether they could respond to any of these. Then studying this, we’ll understand what is the best sequencing of all of these different agents. And obviously, I think AI is going to play a big role in this. And help us to better understand the pathology, the genomics, putting it all together. We have so many different things that we need to converge to work together, and I agree also that the access is an important problem, that precision medicine needs to be brought to everyone, not just to a few selected patients and selected centers.
Phillip Koo, MD [00:08:02] You know, that’s a great point in getting that access to the community is a challenge that I think is not insurmountable. So, we’re gonna turn over to Oliver, and for those of you who probably don’t know, Oliver was at EANM two weeks ago, then ESMO, then AACR, and now PCF. So, I think he’s traveled more miles in that two and a half week period than has ever occurred.
Oliver Sartor, MD [00:08:23] It’s not a sign of intelligence
Phillip Koo, MD [00:08:26] It’s a sign of passion and commitment to prostate cancer. So, Oliver, for many of you who know, has been involved in radiopharmaceutical trials from decades ago when it was not so cool and actually sort of disappeared. Yet, you know, you’ve stuck by it and you’re seeing, thanks to a lot of your work, some amazing, amazing developments. So not just limited to radiopharmaceuticals, but what’s your perspective on some of the unmet needs?
Oliver Sartor, MD [00:08:50] One of the things, Phil, that still bothers me so much is everybody with metastatic disease is going to die. Here we are. We’re pushing out. We’re pushing’ the boundaries. We’re doing’ better and better, but these patients are gonna die. That’s an overwhelming reality, and I wish we could somehow change that in a substantial way. That’s number one. Number two, we do celebrate our victories, and we should. ADT from 1941 was an amazing advance. The ARPI, starting with Abiraterone in 2011, amazing, and really have shown a huge difference. But you know, there are a lot of men who don’t like to be castrated, there’s a lot of men that don’t want to get chemotherapy, and we’re still kind of forcing them down to kind of the chemotherapy and the castration path. I would love to be able to treat patients without castration and chemotherapy and have similar outcomes. That goal is probably too high right now, but I’m always looking for that opportunity. As we go forward, and again with what Maha and Cora both said. You know, understanding the heterogeneity of the disease is so valuable. And yes, we can have kind of a phenotypic, you know, high-volume, low-volume, but looking at genetically, or now we begin to do by Decipher, or maybe gonna do by the ArteraAI, these are incredibly valuable contributions to our understanding of the biology. And I didn’t know until relatively recently, the last ESMO, that the Decipher high group were the ones who really benefited from chemotherapy up front. That I’m perfectly willing to recommend, for those patients who have the Decipher high, they should get the chemotherapy because it really changes the hazard ratio. Anyway, oh my gosh, so much to learn and to keep learning.
Phillip Koo, MD [00:10:27] All right, that’s great. So, we’re gonna move forward and bring on some leaders in the very specialties that join us and sort of help us sort of chart what they see is the future and love to hear your thoughts on this. So next we’re going to invite Dr. Jim Hu to the podium, and you know, Skip said this earlier that we need more urologic oncologists, and I can’t think of someone better than Dr. Hu who is one of the world leaders from a clinical perspective, especially surgical techniques and is also a prolific researcher, which I learned as well. So, thank you very much, Jim, for joining us.
Jim Hu, MD, MPH [00:10:59] Oh, my pleasure. It’s wonderful to be here. Thank you.
Phillip Koo, MD [00:11:02] You’ve spent your career obviously dedicated to prostate cancer, urologic oncology is a huge part of what we need, and we need to help foster that involvement as we move forward. From your perspective, what does the future of urologic oncology look like?
Jim Hu, MD, MPH [00:11:17] Absolutely, so, you know, not to throw out some maxims, but I think about as a surgeon, as a urological oncologist, you know first do no harm, right? And so not to be redundant with what’s already been said for precision medicine biomarkers, but certainly better differentiating who has a potentially lethal prostate cancer versus an indolent prostate cancer. I think challenging paradigms, we heard that over and over again this morning, like Dr. Belldegrun who, you now, seeing his timeline of discovery and being a resident there with him in 1998 through 2004, I think many people, the young people here, don’t even know that he’s actually a world expert in kidney cancer, right? That’s where his academia was. And I remember him doing cryotherapy in a salvage fashion back then for prostate cancer, for radiation failures, and so forth. And so that’s come full circle around again, right, now that we see with focal therapy. And so, that’s just an antidote to say that sometimes you have to challenge conventional thinking and I think also Gina touched upon the USPSTF task force recommendations against PSA screening. So, we were fortunate to look at that data that PLCO put out there and say, look, there’s tremendous contamination in the contamination arm. Also looked this year to be the first to show that there is an increased risk of metastasis at diagnosis, which the New York Times just acknowledged in a front-page article last month. And so, I think the summary is that, you know, it’s just to challenge, conventional thinking, and listen to the patient, right? What are the elements that the patient has in terms of anxieties or survivorship issues from diagnosis to treatment of prostate cancer?
Phillip Koo, MD [00:12:51] That’s interesting you bring up a great point about screening and I think often times were so in the weeds with regards to these different treatments for these men with advanced disease that you know we forget that something like screening could have a huge impact on the trajectory of the disease you know just to be a little provocative. Sometimes I hear urologic oncologists of people say that maybe surgery becomes obsolete in the future you know what your thoughts on that are you going to be out of a job the I might be out of a job as a radiologist.
Jim Hu, MD, MPH [00:13:16] Well, look, I mean, I think if we’d done our job correctly, all of us would be, as a physician, we’d be out of jobs. Prostate cancer would be in many ways preventable, right, like nutrition studies and so forth. And so, the other thing, just to reflect upon what was said earlier in the wisdom of Mike Milken saying that really minimally invasive robotic surgery, intuitive surgical was delayed 10 years, right? And so, our field is one, surgery is one full of dogma. And so, kind of expanding on that, a lot of the variation in technique is what leads to some of these differences and complication rates. But to your point, for example, for the young people, Intuitive has already, they’ve hooked up our surgical consoles to the cloud, and I’m sure they’re scraping our data. So, one day, you probably don’t even need someone doing, robotic surgery is a misnomer, it’s really computer assisted, but it’s truly gonna be autonomous robotic surgery someday.
Maha Hussain, MD, FACP, FASCO [00:14:09] Can I maybe say, you know, and I’m not a surgeon, but I will say this, my, you know, where we sit like the three of us here on the other side of the aisle, and where we see patients coming in with progressive disease, locally uncontrolled disease, especially I would say my bias for younger men is to really take the prostate out. Because again, we’re all biased by our own experiences, but the problem with it is you’re not going to be able to salvage them. Once you’re within radiation and this and that, and then there is local relapse or areas that have not been there. So, I do think we need some kind of proper systems in terms of guidelines as to how to proceed with these things. Someone who’s 85 is one thing else, but somebody coming in, and I have a fair number of younger men who are in their 40s. Actually, my youngest was 37 years old, but with de novo metastatic disease. But I mean, I get patients in the 40s and the 50s, and when they talk to me, my advice to them is take it out.
Cora Sternberg, MD [00:15:05] We are clearly seeing younger and younger patients with prostate cancer, and it’s something that we need to study and understand them and understand their genomics and understand what’s going on.
Maha Hussain, MD, FACP, FASCO [00:15:14] We have actually a project that we’re working on.
Oliver Sartor, MD [00:15:17] I don’t think people understand the magnitude of the problem of recurrent cancer. We talk about prostate cancer CRPC and we have 40, 45,000 patients there. Hormones sensitive, we can argue a little bit, but maybe we’ve got 30, 40,000 there. If you look at the recurrent disease, it actually is probably 750,000 patients in the U.S. walking around right now. Many of them would love to know where their cancer is and they can’t find it. So, you’ve got a tremendous unmet need for people trying to seek what the right alternatives are. So much of the time they just start ADT willy-nilly, but the ADT just suppresses it. It doesn’t really make it go away. So, we’ve got so much more work to do in detection as well as treatment.
Phillip Koo, MD [00:15:59] So Jim, from your perspective, you work very closely in your MDTs with medical oncology. How do you think we collectively take that next step partnering together with MedOnc and urologic oncology?
Jim Hu, MD, MPH [00:16:13] Absolutely. So, I mean, I think one of the things that, and it opens up areas for the young people to think about in terms of their careers, right? So, to my knowledge, and we have venerable medical oncologists here, we haven’t found a target or a neoadjuvant target so that it can work along with surgery, right, like perhaps in some other fields. And so, I think hopefully as the field of theranostics matures, or there are better targets than PSMA, certainly I think we as surgeons need neoadjuvant studies, right. You know, I think we also don’t do enough clinical trials. And so, when we look to the multidisciplinary teams and our medical oncology colleagues, as well as our radiation oncology colleagues, I think there’s a gap, or one could frame in a positive light, there’s tremendous opportunity for surgeons to do more clinical trials, right? And that’s where we would look to our colleagues for that guidance.
Phillip Koo, MD [00:17:05] You know, it’s interesting, I remember, at least for me, in my training, it was always, you know, don’t train too much in a modality, sort of understand and be a disease expert instead. But I think oftentimes the training programs in urology put additional focus more on the techniques of surgery. What are your thoughts on how, perhaps, especially you may need to shift?
Jim Hu, MD, MPH [00:17:28] Absolutely, well, I think that, look, I mean, you bring up a great point, right? Like if you had a prostate cancer service line and trainees were just there to treat prostate cancer, diagnose, treat it, and then follow them when they have metastatic disease administer a doublet or triplet therapy, that truly serves the patient’s best, right, because then there’s not this, hey, should they get radiation? Should they get surgery? There’s a clinical trial, well it’s easier for me just to operate rather than to wait for the trial and so forth. And so. So, I think that’s where the specialty needs to go. However, I think we’re limited in terms of how our training programs, right, are limited to, urology, you train for, GU, kidney, bladder, but that doesn’t, that takes away from this, you know, entire patient or disease spectrum concept that really would serve the patient.
Phillip Koo, MD [00:18:21] So I’ll ask just the three of you. He mentioned clinical trials and being able to tap into that expertise. How do you think that partnership would be maximized?
Oliver Sartor, MD [00:18:35] It starts by working together every day. The idea that I’m gonna go approach a colleague who I don’t even know to begin a clinical trial tomorrow is not the best way to work. The best way work is in a collaborative group and when the clinical trials come, then you know that you can introduce yourself and the trials to the colleagues without it necessarily being a stranger. If you’re just kind of dropping out of the sky, showing up, here’s the clinical trial, really suboptimal. So, creating multidisciplinary groups as part of your center, I think is absolutely key from the beginning, not just when you’re starting trials.
Cora Sternberg, MD [00:19:09] At Cornell, Jim is one of the people I work with, and we have a multidisciplinary group that meets every single week. And if it’s not during the week, if there’s even a holiday, we discuss with each other. And every patient knows that they’re not just having two eyes look at their patient, but they’re also having the radiation oncologist, and they’re also having the urologist, and they’ll have three opinions all together, and the radiologist, everyone is there together to think about what could be the best option for the patient or options for the patients. So, I think that that’s something that needs to be done in many centers. And then if we see that there’s gaps and we need some kind of a protocol that makes sense before surgery, I think that we will have to discuss that together and decide what would be the best treatment to give to patients before surgery.
Phillip Koo, MD [00:19:59] You know, this may not be a popular perspective, but I do think those types of relationships are best cultivated in person. And I know a lot of our tumor boards have shifted to team Zoom virtual. And I do you think it’s a little bit of a lost opportunity and there’s benefits to it clearly. I think we need to find that balance moving forward. And it’s always nice when you have researchers also who join some of these calls.
Maha Hussain, MD, FACP, FASCO [00:20:21] But I think speaking from an academic perspective is different than practice, the community practice. And I think that’s the harder part. I mean, obviously, we work as teams, and many of us actually work in spaces where we have urologists working in the same space. Having said that, I think the hardest part, which is what I see a lot of times from my practice situation, is people coming in from the community. And the question is, how do you spread the word out there? And that’s going to be an interesting issue.
Phillip Koo, MD [00:20:53] So we’re gonna go ahead and now welcome Dr. Neha Vapiwala, who’s a radiation oncologist. And I’ve gotten to know Dr. Vapiwala now over the past few years. And she’s the Dean of Admissions at the University of Pennsylvania Medical School. She has so many titles. She’s also the new president of ASTRO, so congratulations. And on top of all that, if you Google her there’s a picture of her ringing the bell with President Joe Biden after he finished his radiation treatment. So, I know she did not want that out there, but someone put it on the internet, and now it’s out there. So, thank you very much for joining us.
Neha Vapiwala, MD, FASTRO, FASCO, FACR [00:21:28] Thank you for letting me anywhere near this stage of luminaries.
Phillip Koo, MD [00:21:33] So radiation oncology continues to evolve. What is your perspective on where it needs to head in the future?
Neha Vapiwala, MD, FASTRO, FASCO, FACR [00:21:43] So, first of all, thank you, everyone, for having me here, and I would say, on behalf of our specialty, I think the talent of my colleagues and our willingness to collaborate with all of our wonderful specialties that contribute to GU oncology has been and will continue to be a huge strength in our field. And so, on that note, with my surgery colleague next to me, I’ll quote Dr. Blake Cady one of his or paraphrase him, you know. Biology is king, patient selection is queen, and then technology and our procedures are the princes and princesses that sometimes try to overtake the realm but don’t over the long term. And what I mean by that is ultimately our work in translational science and biology is always in my mind going to trump some of the technological advances, which are very important to us as radiation oncologists. We love our adaptive therapies. We absolutely need to be showcasing those techniques and thinking about how AI will, of course, affect and streamline those workflows. But where the real focus should be, again, is smarter patient selection. You heard this morning from Dr. Spratt and, of, course, the legacy of Dr. Feng in terms of all of the work that’s been done from Decipher, Artera, certainly now PAM50 in the BALANCE trial that was reported as the first predictive biomarker helping guide better patient selection, but I’ll give a few other examples. You know, we have, again, when we think about the therapeutic index of safety of radiation and patients who might be more likely to have long-term GU side effects, we have tools like PROSTOX, which was developed by Dr. Kishan and Weidhaas, colleagues at UCLA, using microRNA-based genetic testing to try and determine patients who might be at greater risk for some of those late-GU side effects. We need more of that. We have wonderful work, quantitative imaging and genetic risk modeling from Dr. Siebert at UCSD. And the type of work that needs to be done there to develop those biomarkers for cancer detection for treatment response assessment. We have recently published a multi-institutional collaboration, doctors Tran and Ost, who led the ORIOLE and STOMP trials respectively, working with Dr. Chaudhry, who’s an incredibly talented radiation oncologist at Mayo, looking at the use of PSMA positive extracellular vesicles that might be present together with PSA as potential biomarkers so that you might know and use that to determine the tumor burden in patients with oligometastatic hormone-sensitive prostate cancer to figure out which ones might be okay to just get SBRT alone. So again, this kind of continued refinement, and then more recently, the work with foundation medicine that I’ve been able to participate in thanks to PCF. Looking at patients after ARPI therapy, who may not have the best treatment response to radiopharmaceutical therapy to lutetium PSMA because of the presence of certain tumor suppressor genes and how we might, again, continue to refine. I feel that where radiation oncologists can really contribute is that ongoing science, working with our colleagues, so that every time we do have that patient, we’re giving personalized radiotherapy to the greatest extent possible.
Phillip Koo, MD [00:25:06] So I’ll ask this question for the four of you. You obviously all work very closely with radiation oncologists. From your perspective, where is sort of a nice opportunity to increase that level of partnership, and whether it’s adjuvant treatments or whatever that might be?
Cora Sternberg, MD [00:25:23] I speak to the radiation oncologist that works with us practically every day about every single patient. I don’t think about length of radiation as much as she does. I think more about length of ADT, but we will think about it together. We will discuss it together after looking at the patient, the whole story of the after reviewing everything with our nuclear medicine and radiologists who will look at the scans and look at the PSMA scans with us and we will discuss it again and again after the tumor board.
Oliver Sartor, MD [00:26:00] You know, I say the same thing. We work incredibly closely with radiation oncology. Not just everybody who gets radiation, but somebody might even be considered for radiation. Interpretation of the prior fields, interpretation of the PET scans, interpretation of concomitant therapies, interpretations about the natural history of the disease. There’s an absolute need to integrate our work in medical oncology with radiation oncology, particularly for the early relapsers. You just gotta do it.
Phillip Koo, MD [00:26:27] So Jim, from your perspective, oftentimes it’s surgery versus radiation. And there’s almost sometimes like, it could be hostile, I guess, in certain situations. How do we sort of change that culture? Because I think there’s more overlap here than we recognize.
Jim Hu, MD, MPH [00:26:42] Absolutely. Well, just dovetailing on, you know, I think the previous question, if I may take that one first, and just as an example, again, for young people to think about, you know, Himanshu Nagar did a great job with Chris Barbieri, who’s here, and looking at focal therapy with Tim McClure in terms of, you now, can you give a shorter dose of stereotactic body radiation therapy with focal therapy, right, because we know that there’s undetected foci of disease and the whole point of focal therapy is to minimize toxicity. And so that’s a nice trial that they did, proof of concept. So that’s an opportunity for urologists and radiation oncologists to work closer together and interventional radiology in that regard. To your second question, which is, oftentimes we’re competing for the same patients, right? I think that, you know, and this, there’s not too many urologists here, but as you get older, you realize, and you said this about training programs, is that as surgeon, you’re defined by what your outcomes are, right? But I think sadly, many of us don’t know what our outcomes are because you have to take time to measure them, you have measure them in a patient-reported outcomes fashion. And so truthfully, if you don’t even know what your outcome are, should you be telling that patient you should have surgery over radiation? What I mean by that is, you know, if you’re encountering patients that for whom sexual function is incredibly important, right, maintaining erectile function. Then you have to put the patient first and say, look, my radiation colleague may be able to do this better, particularly in older patients, right? And so I think that’s where, and again, multidisciplinary clinics, I was fortunate enough to be with Oliver when Phil recruited us both to the Dana-Farber, and in that setting, it was nice, because I remember Paul Nguyen, who’s no stranger to the PCF, you’d see a patient that had a prostate size of larger than 60 cc’s, and obstructive symptoms, if they’re already present, could be worse, right? And so that’s an instance where there was a consensus reached and that patient may be better served by surgery.
Neha Vapiwala, MD, FASTRO, FASCO, FACR [00:28:36] And if I might just add, I think as radiation oncologists, we have a long history of really focusing on how do we de-intensify, how do we minimize the unwanted impacts of our treatment. And so, we already have that baked in from our training. And I would say that in that regard, creative solutions such as FLAME, hypo-FLAME, looking at dominant lesions, how do we focus the radiation where it needs to be, has always been, I think, front and center. It’s just part of how we view things. And so. I think the opportunities for pairing these increasingly targeted and adaptive forms of radiotherapy with novel systemic therapies, so going beyond traditional androgen deprivation therapy. I mean, I think this is absolutely the opportune time as we think about T cell engagers, we think about CAR-T, sorry, Maha, and other combinations that we could have. You know, these are, I think, the questions that will lead us into the next decade.
Phillip Koo, MD [00:29:34] So, Neha, you started your term as president of Astro, so we know you’re gonna prioritize prostate as the only initiative for your tenure. So, tell us more about what you are focusing on as an organization, as a society.
Neha Vapiwala, MD, FASTRO, FASCO, FACR [00:29:48] Thanks for that question. This actually ties into what Mike Milken was talking about this morning, I think, and others have alluded to. We’re in a time where I think trust in medicine and science is, a least in my lifetime, at an all-time low. And we’ve had our challenges as physicians and how we’re portrayed in the lay media. But right now, this sort of global sense that facts are not facts and that science cannot really be trusted is, to me, one of the scariest things happening. So my meeting theme and one of things that I’m really gonna focus on, data to dialogue, is making sure that the way in which we disseminate our science, you know, it’s wonderful in rooms like this where we all sort of understand each other and all of our acronyms and our lingo, but I think the reality is for stakeholders ranging from not just patients and loved ones, but the legislators and the policy makers and the philanthropic donors, we need to have a better way of making sure that not only do they understand the science but that they’re engaged with it from the beginning and that we can expect everyone to be interested in our niche little thing we’re doing. So, if we can do a better job of making sure the value of what we’re doing even if it seems obvious to us. Is constantly communicated, I think it will elevate all options for us. And so that’s a key focus, as is for us really thinking about harnessing AI, thinking about ways that we might supplement large prospective randomized clinical trials, which are absolutely wonderful and the gold standard, but not practical in every way. And particularly with the funding environment, how do we think about leveraging AI and goodwill and cooperation to get some real-world pragmatic data, have people that contribute? I know there’s a new ASCO Google Cloud collaboration that’s been announced in the news. I think there’s lot of potential for us to partner with these other industries to think about big data in a way that we haven’t before and generate answers or at least hypothesis generating questions more readily and much more rapidly than we have historically done. I just don’t know that 15-year outcomes waiting around for that works anymore or is sustainable.
Cora Sternberg, MD [00:32:13] And when we have outcomes, I think we need to project it in a way that is real news. People don’t believe the news anymore. There’s too much fake news. I don’t know what to call it anymore.
Neha Vapiwala, MD, FASTRO, FASCO, FACR [00:32:26] Distractors.
Cora Sternberg, MD [00:32:27] Distractions in the news. And they need to know who is doing it, and why are they saying this, and who the people are, and what are the results, and where do they come from. I think that’s so important.
Phillip Koo, MD [00:32:38] You know, I think that’s a great point. There are a lot of distractors in the news, a lot of distractors in the social media, and they say it comes from research, but what research is it and how do we make sure a lot our patients aren’t being deceived by what they see in some sort of tweet or scroll.
Maha Hussain, MD, FACP, FASCO [00:32:51] Which is why I think patient education is very critical.
Oliver Sartor, MD [00:32:55] One brief little hats off, PCF has done a beautiful job with engagement with their donors and those individuals who’ve been supporting PCF over many, many, many years. And PCF was the first one that really brought people from all walks of life, from the scientists to the philanthropists to the bioengineers, the small biotechs, all in one place and created, I’m going to call it a gumbo because I’m from Louisiana. It’s a really spicy, nice gumbo. And people energized from one another. They create better when they learn from others.
Neha Vapiwala, MD, FASTRO, FASCO, FACR [00:33:28] Oliver, thanks for that point. That’s exactly the model that we want to follow.
Phillip Koo, MD [00:33:31] Spicy gumbo. I like that.
Neha Vapiwala, MD, FASTRO, FASCO, FACR [00:33:32] I know, I haven’t had this in a while.
Phillip Koo, MD [00:33:34] So now we’re going to welcome Dr. Emmanuel Antonarakis to the stage, and he’s a brilliant medical oncologist. I think it, I was looking at your CV, how many publications, 350, 400, and you still have a lot more time left, but now I’m going to put you up with your peers on the stage and hopefully you could say something that…
Emmanuel Antonarakis, MD [00:33:59] Well, it’s not going to be easy. I was making notes on my cell phone, and I had to scratch them out one by one because I didn’t want to be duplicative. But I want to make a few points. One is, I’d like us to focus on BCR, biochemical recurrence. That’s something that I’ve always had an interest in. I think Chuck Drake said it yesterday. It’s a third or second chance for a cure. And let’s design trials for those patients. Let’s try to design hormone-sparing trials for those patients. Oliver, you talked about getting rid of hormone therapy, what better place than in the BCR setting, or maybe the micrometastatic PSMA positive, which used to be the old BCR setting.
Oliver Sartor, MD [00:34:36] Some interesting KLK2 data out there just to give that another day.
Emmanuel Antonarakis, MD [00:34:39] We have liquid radiotherapies now. We have immunotherapies that actually work. So, let’s do that. The second is ADCs. I think we have not cracked the ADC code yet, and I think that we should. In other cancer types, including other GU cancers, the ADCs have made it into the first line setting in bladder cancer. We have many attractive targets. We’re beginning to learn about more and more. And yet we don’t have any successful ADCs. So, let’s prioritize that. I’d like to see more research on the ones that we’ve heard already. STEAP1, PSMA, but also B7-H3. There’s a large proportion of people in this audience that are working on B7-H3 as an ADC target and maybe an immunotherapy target. So, I’d like to see you more about that. We haven’t heard much about the proteome at this meeting. And we’ve heard about the genome, the transcriptome. And yet, many of our therapies are targeting proteins. They’re not targeting genes or transcripts. And there are very elegant ways, and I’ve had the pleasure to work with Justin Drake at the University of Minnesota, where we can actually interrogate the proteome in blood, either from circulating tumor cells or from circulating exosomes. And those circulating proteomic markers are gonna be very reflective, I think, of the protein expression in the cancer. So, let’s see if we can capitalize on that. One short word about MRD, you know, we don’t talk about MRD much in prostate cancer. When could it be helpful? And I think one place where it could be helpful is in the patient who’s had the initial doublet or triplet systemic therapy whose PSA has gone down to less than 0.01, where we want to make a truly informed decision about whether to de-escalate or completely stop the therapy. We all have patients, especially the younger men, the ones in their 50s, they’ve had three-year complete response. Everything melts away on the scan. Their PSA is less than 0.01. They don’t wanna be on ADT for the next 15 years. So, what if we had an MRD marker that in the context of an undetectable PSA could detect circulating nucleic acid or some other tumor derived thing and we could use that to deescalate or not. So, I think that’s something very interesting. And then the final thing, and we haven’t mentioned Dr. Coffey yet, Don Coffey. So, I’m going to channel my inner Don Coffey. I had the pleasure of meeting him. Do we need to continue LHRH agonist or antagonist therapy when we treat people for castration-resistant prostate cancer? This sounds crazy. If I was early in my career, I wouldn’t have the nerve to say that on this stage. But could we design responsible and safe trials whereby the randomization is not the next thing that we’re going to add. But whether or not we can discontinue ADT. And I would love someone in the audience to start thinking about that. And again, we have to build in the safety aspects because we don’t want to hurt people, but there might be a subset of patients were stopping the ADT and pursuing that next CRPC therapy might be the way to go.
Phillip Koo, MD [00:37:53] I think we could probably spend an hour talking about those four topics, but I’m going to turn it over to Maha.
Maha Hussain, MD, FACP, FASCO [00:37:58] Yeah, no, so you know the A-DREAM trial. So the A-DREAM is stopping after two years What I have many patients that I counsel like usually I say once we’ve reached a five-year mark And especially if they were low-volume not horrible disease, whatever take a treatment holiday And I will tell you right now I have several patients who are two years out of finishing ADT until today their testosterone did not recover. So, I think we have to be mindful of that. Now, the question is maybe tomorrow it will go up, but the hard part is there is this almost like a permanent andropause phase that’s happening with those patients who have been on treatment for a while.
Cora Sternberg, MD [00:38:38] Well, I think especially this goes with age. I mean, I use a lot of intermittent androgen deprivation therapy. And patients in their upper 80s, they don’t recover for years. When you stop therapy after they’ve had a PSA of zero many times and they’re 50, they probably will recover earlier. But looking at MRD in those patients would be really a wonderful thing to do. Are we missing something? We’re about to publish a paper with Andy Armstrong and others showing that patients have PSA 0 if they’ve had an ARPI, 20% of them may have radiographic progression even though their PSA is 0. So, you can’t only depend on the PSA, and we need to remember that too. So, making the circulating tumor cells better so that we can look at that and look at MRD makes a lot of sense to me.
Oliver Sartor, MD [00:39:29] No, I agree. I’ve actually had some comments with the Marriott folks who presented some data at the NRG meeting a couple months ago, and it was very impressive. You know, the PSA is actually the marker of a well-differentiated cell. The PSA-producing cell is not the one I fear. The one that I fear is the one that makes just a little bit of PSA. We don’t have good ways to detect it. And it turns out that MRD might be a better way. And we’re already shipping samples back and forth and getting collaborations set up, so I love the idea.
Phillip Koo, MD [00:40:01] So Jim and Neha, his comments about BCR, thoughts on that? His comments about the BCR.
Jim Hu, MD, MPH [00:40:07] I mean, I think that certainly for surgery, there’s different variations in BCR. Some of that, again, being honest, there’s a different quality of surgeries being done, is a .1 due to leaving behind benign tissue, right? So, I think, that’s why you see some people advocate .4 is a biochemical occurrence, less than .2, less than 0.1. I think there’s lot of surgeons that don’t like ultra-sensitive PSAs. I prefer them, but again, it can speak to not wanting to talk to your patients early about what those trends are. So at least from a surgical space in BCR. You know, and then I’d look back to really the work that Dr. Walsh did, right? A lot of the natural history of prostate cancer came from leaving those men with biochemical recurrence off of ADT, right, the natural history of progression that the guy from Mississippi escapes me now that’s been cited 3,500 times. You know biochemical recurrence to metastasis was the timeframe for that, right. And so, I think that there’s a, like I said, there’s convention that needs to be challenged. There’s probably a subset of patients that don’t, once they get ADT for a while, you can stop perhaps for a long time, right? And it harkens back to what Cora said that prostate cancer is a heterogeneous disease.
Phillip Koo, MD [00:41:20] So Neha, it’s interesting, you know, Emmanuel talked about the chance for a second cure and mets directed therapy, I think, was thought of, oh, as an opportunity to cure. But it’s just interesting, if you look at those trials, all those patients recur at some point. So, what’s going on? Yet it’s become standard of care, even though, I agree, there’s no level one data.
Neha Vapiwala, MD, FASTRO, FASCO, FACR [00:41:39] Well, exactly, and so, you know, the INDICATE trial, which I’m leading, it’s trying to ascertain exactly that. And I couldn’t agree with you more in the BCR population. For the reasons that Maha stated earlier, these are young men oftentimes, you now, and so already the desire to minimize treatment of any form, particularly radiotherapy and particularly anything that messes with the hormonal access, the stakes are very high in these patients in terms of quality of life and how it affects their work. So, answering those questions at a time where, again, patient clinical trial accrual is at an all-time low, from what I’m hearing, again across the United States and perhaps globally as well. How do we design a study that is then, to some degree, pragmatic? When you’re dealing with a BCR population and you have clinics where the patient is anxious after two rises and they’re barely at 0.2 and everyone’s ready to move forward with treatment. It’s very hard to enrich for the types of patients at the same time ethically. You don’t just wait around if you know that you can treat them. So, I think that’s something we have to resolve as a community and figure out what is the population where this is reasonable in sample sizes that are not going to take, you know, many, many years to accrue and read out. So that’s, I think, the main challenge, to get that level one evidence.
Phillip Koo, MD [00:43:05] Emmanuel, last comments.
Emmanuel Antonarakis, MD [00:43:06] Last comment, we’ve got 45 seconds before Dr. Hofman. You know, I just want to talk a little bit about the physician-patient interaction during that visit with the BCR. You know I find that to be the most distressing visit to the patient. Much more distressing than the one where he goes from hormone-sensitive to castration-resistant because they’re expecting that one. When you’ve got metastatic disease, you’re expecting something. You’ve been groomed, you have time to think about it. The visits that take the longest in my medical oncology clinic are the BCR visits, and those patients are motivated to go for a cure. And they believe that it’s possible, you know, sometimes the physicians believe that it’s possibly too. And if we can design studies on the one hand with hormone sparing approaches, but on the other hand, with a finite amount of escalation, for example, ADT, enzalutamide, plus a PARP inhibitor in a BRCA2 patient with a high-risk BCR. Intense therapy, final duration, and then stop. Those patients would sign up very, very quickly.
Phillip Koo, MD [00:44:12] Great, so now we’re gonna move on to Dr. Hoffman, who’s last but not least. We are gonna have some time for Q&A, so if you have questions after, Michael will have some time for that. Michael, it’s hard not to see a headline from UroToday or whatnot after every meeting and not hear about something that Peter Mac or the Australians are doing with regards to radioligand therapy or whatnot, so thank you very much for joining us. Nucmed is near and dear to my heart. I think there’s a lot of challenges, but the future is bright as long as we create the future. And I think we need to define it and make it work. So, what is your vision for the future for nuclear medicine?
Michael Hofman, MBBS [00:44:54] Yeah, thanks for putting nuclear medicine on the board. I think we could divide this into imaging and therapy, and we might just consider them separately. Maybe we’ll start with imaging. And in medical school, we’re taught more is missed by not looking than not knowing. And I think, we still don’t use imaging to its full capability. We think of imaging as counting lumps on CT and MR, and some people use PET scans just to count lumps as well. PSMA has shown us that we can actually characterize cell surface reception. Expression of PSMA, use that to choose who needs PSMA radioligand therapy. So, we’re now using it as a disease characterization. But we don’t use it fully. And we can image just about any cell surface target beyond PSMA. And the technology to do this is really evolving quickly. So, we can have an espresso machine. You press the PSMA button, out comes gallium PSMA. But if you’re treating with an ADC or an antibody or any targeted therapy, we ought to be imaging that target and not treating blindly because tumor heterogeneity is the fundamental limitation. So, if you’ve got an ADCs or an antibody and only half your disease is there, expressing that target, you’re gonna fail. So why have the toxicity of that therapy when we have the technology to predict that upfront? And on the imaging side, the technology is just changing so quickly. When I was a medical student, there were two PET scanners in Australia, so you could not get a PET scanner. Even if you had lung cancer, you barely got a PET scan. Certainly, no one with prostate cancer got a PET scan. Fast forward 27 years, there was I think 150 PET scans in Australia. So, it’s grown enormously, and we’re just installing the first GE Healthcare total body PET scanner at Peter Mac at the moment. So, a standard PET scanner scans about 30 centimeters length of a ruler. Does that six times, you stitch it together, you get your image. And these new PET scanners, you scan the whole body in one go. So, we’ll be able to do that in one minute. When I was a medical student, the PET scan took 90 minutes and then the computer would process the image overnight. They were that slow. So maybe a PET scanner did four scans a day. Now on a total body PET, we can really revolutionize the throughput the patient experience and we can start to image multiple targets. This concept that we can’t do an FDG and a PSMA. I don’t see why we can’t image three or four targets, if that’s relevant for the patient, get the whole-body overview, and then quantify the target. How high is it? What’s the volume of it? When we think about dosing an ADC or an antibody, I think most trials dose per body weight. It actually doesn’t make sense. If that antibody or ADC is taken up by tumor, and tumor can vary by a hundredfold, You want to give less drug if your tumor volume is lower and maybe 30 times more drug if your tumor volume is 30 times higher. We’ve never had the technology to do that before. We could just weigh the patient, yep, get a per kilogram dose, but now on a PET scan we can tell you there’s 1.25 liters of tumor. You can then integrate that into your drug approach. And I think this really has an approach to the way we revolutionize targeted therapies.
Phillip Koo, MD [00:48:08] You know, it reminds me of, so more imaging, better imaging kind of reminded me of Will Ferrell, that more cowbell skit. I don’t know if you guys are familiar with this. All right, so what about the therapeutic side?
Michael Hofman, MBBS [00:48:19] Therapeutic side. I think we’re just in the beginning with lutetium PSMA. It’s kind of showing us what we can do, how it’s coined new atoms, new targets. So, there’s lots of new targets, new atoms being explored. Mike Morris asked a very good question with all these radionuclides. How are we going to choose between terbium, actinium, lead, lutetium, et cetera, et cetera. And Dr. Lapi showed us a whole range of different radioisotopes. That she can make in her cyclotron, but I think we can boil it down to alpha, beta and auger, they’re the three classes, and we really don’t know out of those which is the best at the moment. So, there’s much work to be done, but probably it doesn’t make too much difference between this beta or that beta. That’s maybe a commercial supply issue, sometimes a radio labeling issue, but it’s going to be a class effect. I think the revolution is going to come in combination theranostics, not giving one on its own, and that’s been half focus for the last decade beyond Lutetium PSMA, and we’re still working out what are these ideal combinations and where is it synergistic rather than just additive. And when we talk about cure and BCR, you know, I would throw some radioligand therapy into the mix because we know you cure people with external beam radiation.
Neha Vapiwala, MD, FASTRO, FASCO, FACR [00:49:38] Uh, no.
Michael Hofman, MBBS [00:49:38] I think you do, early stage. You do, you cure people just like you cure people with surgery. So, there’s a proportion…
Neha Vapiwala, MD, FASTRO, FASCO, FACR [00:49:44] Oh, I thought he said kill.
Michael Hofman, MBBS [00:49:45] No, no.
Neha Vapiwala, MD, FASTRO, FASCO, FACR [00:49:47] I was like, what?!
Michael Hofman, MBBS [00:49:47] Cure, cure, apologies for the Aussie accent.
Neha Vapiwala, MD, FASTRO, FASCO, FACR [00:49:53] No, that’s fine, okay. That’s better.
Michael Hofman, MBBS [00:49:55] No, no, no. You cure patients. So, there’s a proportion of men out there with BCR that can be cured with a radiation-type approach, and radioligand therapy is probably part of that mix, but it’s not everyone. It’s a small proportion of patients, and we don’t want to have the light side effects of giving systemic radionuclides to everyone, so we need to work out how to do that in a nuanced approach. And I think the aim for radioligand therapy then is, actually let’s do it as a cure. And it could be adjuvant early on in combination with your external beam radiation so that you can decrease your fields, decrease side effects, or it could in combination with surgery like we do with a LuTectomy or in the BCR space.
Cora Sternberg, MD [00:50:39] Or with immunotherapy.
Michael Hofman, MBBS [00:50:43] Or various combinations.
Phillip Koo, MD [00:50:44] So let’s explore this synergistic combination idea. So maybe Oliver, I’ll start with you. How can we harness that synergy and are there any signals that tell you a synergy might exist with a certain other treatment.
Oliver Sartor, MD [00:50:57] You know, so we haven’t fully characterized the cells very well, and that’s, we actually just got one of the Challenge grants, and part of the key element is to understand the heterogeneity from the beginning. It was mentioned in B7-H3, there’s going to be a mention of STEAP1 coming up, there is going to of course be KLK2, there is going be PSMA. Some degree of heterogeneities exists in many, many of these cells, and we don’t have a good feeling for it today, and it would be better if we could characterize it. I think if we have kind of AR gate kind of approach, we can knock off the PSMA, and then we knock off a KLK2, and maybe we have the B7-H3 sort of in reserve, then we can create better synergy than just sort of slap-dash do A, B, C. So, the characterization of the tumor at the very beginning of therapy, to me, is a critical element, and we need to do it better.
Phillip Koo, MD [00:51:42] Any other thoughts from the medical oncologists on our panel?
Cora Sternberg, MD [00:51:45] I agree 100 percent with what he’s saying, but I think that this is where AI is going to help us. They’re going to help with the right sequencing, the right combinations, and they’re going to do something a little bit more than what we’ve been doing, I hope. That’s my hope, anyway.
Emmanuel Antonarakis, MD [00:51:59] Yeah, I just want to go back to something that my friend Oliver said. So, a few years ago, it might have been maybe five or six years, Oliver, you had this slide with that, the Robinson cell paper with all the different molecular types, and you said the thing I love about radiation is it kills them all, right? That may or may not be true, and we need to try to figure that out, because the underlying genomics of the cancer may make some more susceptible to radiotherapy and others less susceptible, and then there’s a tumor microenvironment as well, the microenvironment versus lymph node versus visceral site. So, I think we do need to understand that aspect of the equation as well.
Oliver Sartor, MD [00:52:34] If you don’t deliver a good dose, it’s not gonna be a good cell kill. And one of the beautiful things about both alpha’s and beta’s, you can overcome to some degree the micro heterogeneity that you can deposit on a cell here and possibly kill the cell there with the crossfire. That’s one of beautiful, beautiful parts about the radio pharmaceuticals. But we don’t even fully understand who we’re treating and the evolution of those targets in time and space is something we need to learn more about.
Maha Hussain, MD, FACP, FASCO [00:53:01] I think, ultimately, a multi-targeted strategy. This is not about, this is my baby, that’s my baby and therefore my baby’s gonna do the best job. It doesn’t work that way. I think we need to market multi-targeted strategy and the right clinical trials because we’ve all like used PSMA, you know, like Pluvicto, the treatment. And the same patient, and I usually do conventional imaging and PSMA PET, and you see some areas go away, some areas still awake and growing. So that is not gonna be one treatment that’s gonna solve the problem.
Phillip Koo, MD [00:53:36] Neha, Radonc and Nucmed, a lot of synergies from there. Your perspective and thoughts on that.
Neha Vapiwala, MD, FASTRO, FASCO, FACR [00:53:42] Well, I think this is where I’m really grateful to work with my colleagues at SNMMI. And obviously, internationally, I think there’s a lot to be learned from each other. And obviously depending on where in the world you practice, it might be under the realm of one or the other discipline. But the reality is we absolutely need to work together. And particularly when it comes to dosimetry, as Oliver mentioned, I there’s a lot of unanswered questions. And as we start looking at EBRT plus radiopharmaceutical combinations for residual disease, for refractory lesions. That’s where really, we need to understand what is it that we’re giving these patients and how might we be impacting their ability to get future systemic treatments, particularly with respect to the marrow.
Phillip Koo, MD [00:54:28] All right, so let’s open up the floor to some questions. I think we have five to 10 minutes for any questions.
Joël Pointon, MPH [00:54:36] Joël Pointon, I’m a prostate cancer patient advocate with SWOG and I’m also a prostate cancer survivor having been diagnosed six years ago with Gleason 9 stage four. So, I wanna say thank you to everybody in this room and everyone that came before you, that I’m able to be here today. My big concern is that as a patient, most patients are diagnosed at age 66. They’re in the Medicare system. 54% of enrollees are now in Medicare Advantage programs. If you, like me, had to survive through Medicare Advantage, you get a no for everything that you request in the way of a new treatment or a clinical study. I was lucky enough to have a master’s in public health. I could write my appeals and win them. I don’t think everyone is enabled at that level. So, what do we do when we’re developing these wonderful treatments and clinical studies? What do we to ensure that people have access to them?
Phillip Koo, MD [00:55:54] Really challenging question. I don’t know if there’s an answer, so I don’t want to put anyone in the spot, but if I have to, I will.
Maha Hussain, MD, FACP, FASCO [00:56:00] Yeah, no, I mean, I think the reality of it is this. This is policy, and this is why the different societies would actually, we used to go meet with Congress and then try to advocate for it. The bottom line is insurance coverage and providing access to care. And I always say, how in the heck in the land of the free you have the right to bear arms, but you have no right for health care. It makes no sense. So, keep pushing, and I do think making sure that your voices are heard by Congress is going to be very critical.
Phillip Koo, MD [00:56:32] And you know, and one thing that I think we should remember is value equals outcomes over patient experiences. And the more we can maximize that value, the better we’ll be able to advocate for those therapies and reimbursement for those once approved.
Cora Sternberg, MD [00:56:45] But in the U.S., I would say that we advocate for our patients, and not all of our patients have master’s in public health, and we are always advocating for them if we think it’s the right thing to do. I worked in Europe for many years where it’s very easy to do clinical trials there, but every single drug is given for free. Even the prednisone is given for free there, so the people have actually more access to the clinical trials than here. It’s easier sometimes and that’s why so many trials are done in Europe.
Phillip Koo, MD [00:57:12] Yes, and Australia. Go ahead over here.
Unknown [00:57:16] I just wanted to agree with something that Emmanuel said that we want to get away from probably long-term antigen deprivation therapies, but we shouldn’t throw out the idea of short-term intensive therapies that may or may not use androgen depravation. It’s a modality that I think creates vulnerabilities in the tumor cells. We need to understand what those are and then use those combined with, and it may make a difference what the underlying genomics of the tumor is, et cetera. But short-term cycles, we do want to use, we don’t want to not use androgen deprivation therapy if it’s going to be useful, but we do avoid long-term because it probably isn’t that beneficial overall.
Michael Hofman, MBBS [00:58:01] And we might want to consider just the role of imaging, when to stop treatments. You know, a complete response on a PSMA PET in some settings, may be a good biomarker or with other radio tracers, above and beyond what we have with PSA just at the moment. And it may be for many of these treatments that a short course or a more intermittent approach is better than too much. I think PSMAAddition is up after this session, and I think in that trial, probably six cycles of lutetium and PSMA. Pluvicto was too much. So, we need to use our technologies, not just imaging, also liquid biomarkers to know how to de-escalate. Because I think sometimes if you space these treatments out, the quantum benefit may be longer than if you just give it and wait for progression.
Atish Choudhury, MD, PhD [00:58:54] Yes, so thank you all so much for all your insights, and thanks so much, Maha, for highlighting A-DREAM. Emmanuel, as you might be aware, we’re collecting self-reDNA in that study to look for MRD at the time of interruption, but also during the off-treatment phase to see if that might predict, again, the patients who are going to recur. So, and I really want to credit all the people in the room who made this small study happen to give us some preliminary data to then help design the next trials to then see how well patients can remain off treatment with the eugonadal testosterone. So, my question for the group is that in designing these de-escalation trials, the problem that we’re running into is a good problem, which is that the patients who have this exceptional PSA response actually live for a very long time. And so, designing a trial around non-inferiority based on kind of traditional statistical parameters becomes completely infeasible if the median survival of the patients that you’re looking at is something like nine years, Which is kind of what it is. So, one question is, do you think that there is a trial paradigm where we can answer these questions with a smaller number of patients and shorter readout and make the group feel comfortable about these deescalation strategies? And then the second question, is there some funding strategy that we can use to keep trials open a lot longer to be able to follow things like CHIP and late MDS and things like that for PSMA edition. So those are my two questions is like, how to change the paradigm of deescalation and then second, how to keep trials open longer and collecting data.
Oliver Sartor, MD [01:00:39] You know, I might jump in on the first one, and Chris Sweeney and myself and a couple of others wrote a pretty long editorial in European Urology, and I think that we’ve come into a paradigm of time to progression, in part promulgated by the prostate cancer working group and more, that is somewhat flawed. Because the truth is, you want to be able to have a normal testosterone and no intervention as a positive outcome that is achievable, and you don’t have to wait 29 years to be to do that. Waiting until time to progression is very problematic. I think we need to change the endpoints. It’s difficult because the FDA has not yet come around. But in the meantime, the de-intensification is very important. It’s what our patients want. And I think that we can do it even better tomorrow than we do it today.
Phillip Koo, MD [01:01:24] Great, we’re out of time, Dan. I’m sorry, he’s like, oh, yeah, we are out of time, sorry, I was given the death X. So, thank you all, and we’ll move on to the next session.