Evolution of Prostate Cancer Research: From Prognostic Models to Biomarkers and Beyond - Michael Morris

April 25, 2023

Michael Morris joins Alicia Morgans in a discussion on the evolution of research in prostate cancer. They speak about the transition from relying on prognostic models to using biomarkers and discussing patient selection criteria, which has led to the explosive growth in the field, with new standards of care and questions arising every year. They also discuss the growth of international collaborations and partnerships between academic groups, pharmaceutical companies, and foundations. They emphasize that the multifaceted world of research is yielding efficient results, with room for improvement and express excitement about the contributions of young researchers in advancing the field. They discuss the arc of research in prostate cancer and where it is headed. Dr. Morris shares how the standard of care and treatment options have changed throughout the years due to clinical trials. The two also discuss the impact of COVID-19 on clinical trial participation and the future of telehealth and remote care in trial design.


Michael Morris, MD, Medical Oncologist Clinical Director, Genitourinary Medical Oncology Service & Prostate Cancer Section Head, Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

Alicia Morgans, MD, MPH, Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts

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Alicia Morgans: Hi. I'm so excited to be at ESMO 2022, where I have the opportunity to speak with Professor Michael Morris about his vision on the arc of research in prostate cancer, and how we have moved from where we were really relying on nomograms and some pretty basic constructs to predict where we were going to be in terms of patient prognosis and outcomes. And now, we're actually integrating some real biology with a plethora of clinical trials. Thank you so much for being here.

Michael Morris: Thank you for having me, Alicia. It's a pleasure as always.

Alicia Morgans: It is a pleasure. So this is something that I think is near and dear to your heart, as you've watched the community really evolve in terms of our clinical trials and our ability to take care of patients. Tell us what you've seen.

Michael Morris: Where we are now, and if you just look at ESMO 2022 as an example of it, we have data on new diagnostic techniques, including both imaging, genomic, liquid biomarkers. We have many trials now in which we have real opportunities to debate the merits of multiple drug families, as to how they should be combined or sequenced for the same patient populations.

And so we've gone really from, if you go back let's say 20 years ago, where meetings were limited to prognostic models because we didn't have those biomarkers, and therapeutics that were basically docetaxel for mCRPC versus hospice and supportive care, to now discussions of patient selection criteria using any number of different biomarkers in order to explore hypotheses of PARP inhibitors, various chemotherapies, radiopharmaceuticals, immunotherapeutics.

I mean, it really shows you how innovations based on our understanding of the biology of prostate cancer has blown open our meetings to be so much more productive and interesting. And to look at the explosive growth, where we have a new standard of care now pretty much every year. Sometimes two, three new standards of care every year, and new questions posed by disease that now we need to re-stage based on imaging technology, we need to reconceive our prognostic models, we need to reconceive our therapeutics. We have lots of tools to do that reconceiving with. It's really a pleasure to see how the field is now really exploding with possibilities.

Alicia Morgans: One thing that I thought was really exciting at ESMO 2022 is that we saw side by side presentations presenting pivotal data from pharmaceutical companies, right, side-by-side with a cooperative group, and federally supported research by academic groups, and this has been growing over the years with all of us really coming together and doing this work. It's not just one side or the other. It's really collaborative even with correlatives sometimes being funded within pharmaceutical companies, by federal or other foundation funding. It's just very exciting to see such an interest and a partnership that has evolved over the years.

Michael Morris: What also amplifies that multiplicity of vehicles for doing clinical trials is the internationalization of research, so that you can come to an international meeting and see how those models work so well in, or different countries' models are working really well. That, especially for the US investigators, to see trials like STAMPEDE, nationally funded research, highly efficient trial design, that every meeting yields either a new standard of care or a new way of appreciating an older one. I think we now have the opportunity to learn from each other, to contribute to each other's research in ways that we couldn't before.

Maybe some of that also has to do with recognizing through COVID, that electronic communication, it can actually be productive, enhances collaboration. I don't know how many people are at ESMO in a virtual sense. My sense is though that we've all learned to work together through the pandemic in ways that will allow us, even in a more post-pandemic world, to continue those kinds of collaborations. But also, we recognize that there's a role within each country for different modalities of research. There's some kinds of research industry does quite well, others that can only be done through the NCI, or through Research UK or some other vehicle, and that there's a role for each of those participants and stakeholders that the academics can play. It's really quite a multifaceted world now, and each of them yielding results very efficiently.

Certainly, we could be more efficient. It's not that we don't have room for improvement, but I'm struck by this meeting, by how many things there are to talk about, and you'll hear, "Well, at the next meeting, we're going to present this aspect of these data, and at the following one another aspect." So there's so much discovery now that you can plan out what you're going to present at the next set of meetings. I really don't think we used to have that much data in order to plan it more than one meeting ahead. It's an interesting world.

Alicia Morgans: It is, and to your point, the international collaborations could be seen on the acknowledgement and thank you slides for several of the presentations. You could see funding is coming from multiple different countries, from foundations, from federal funding or country based funding, and then pharma may put some support, or companies like Veracyte participating in STAMPEDE, and it's truly an international collaboration and an interest worldwide to really advance the field. What I also find really encouraging, and would love to hear your thoughts on this, is that we did see some postdoc presentations. we saw young people really excited, and contributing so immensely to the field that in some ways, the more senior of us continue to contribute, but to see the junior investigators coming in and contributing is just really, really rewarding.

Michael Morris: It most certainly is, and I think we can do even better on that front, to be honest. I think there are many people who get a lot of podium time, but there are junior people really eager to make themselves known, have a huge amount to contribute, and just need their careers to be fostered. And it's certainly good to see at this meeting that is being done, and I think that it should actually be encouraged more. There should be some reward system for a senior person not presenting. I don't know how that would work to be honest, but it without a doubt is encouraging to see the junior people up there, the postdocs, the trainees, presenting data for one of the many different facets of a particular trial or project that can be allocated to them so that they get the recognition for the work, and they can also learn that we work in a field in which opportunities are given.

Alicia Morgans: Absolutely, and a field in which they can continue to contribute for a long career, which is something that will give back dividends, I think, to all of us. And as we think about this arc of where we've been and where we are now, where do you see us going?

Michael Morris: I think that there's a major transformation that has bubbled up at certain meetings as little pops of excitement that will become more and more prevalent as we move forward, and that is the use of artificial intelligence to amplify our own capabilities to understand data. We saw that at GU ASCO in relationship to pathology interpretation. We probably haven't seen enough of it in terms of the imaging understanding using AI assistance.

And we saw it at a general ASCO meeting in which large reams of clinical data were being processed in order to understand real world practice and outcomes, so I think that there are many domains in which there's work that's now being done in order to better appreciate and better extract the data from many of the data sets that we have, using to computing technology to really yield results that otherwise we just wouldn't be able to wrap our minds around in terms of the data understanding or the processing.

Which could be transformational. It could also allow, in terms of AI as it's applied even outside of the clinical setting, access to interpretation of pathology and of imaging and of medical decision making in areas that may have a dearth of expertise, and a dearth of medical resources otherwise. And I think that that probably is just brewing, and as you look forward another 5-10 years, there'll be more and more about that in many different domains of what we do in prostate cancer.

Certainly from a genomic standpoint, every meeting now we have a new application of genomic interpretation off clinical data. But to synthesize the genomic data with imaging data and the pathology data and the clinical outcomes is going to take a lot of computing technology and computing science, and I think that we're just at the tip of that iceberg. There's a lot more to happen on that front.

Alicia Morgans: I agree, and I really look forward to those advances. One thing that I have seen over the last few years, especially I think maybe because we have opportunities to make decisions among different treatments, we are increasingly focusing on how do we effectively control this cancer while we also maintain the patient's function and life? Not just their quality, but the things that they want to do, their function and ability to get their lives done. And it's so interesting to hear, even in conversations of early drug development, how is that? What's the toxicity like? In a way that we're not just saying, what are the AEs, were their deaths associated with this. We're really asking, is our patient going to be able to tolerate this treatment? Is it something I want to use? If not, we're going to go in another direction, and that's exciting.

Michael Morris: I think that with that will be an additional incorporation over the next 5-10 years of expansion of telemedicine and telehealth into the clinical trials arena, so that those PROs and levels of functionality will be remote monitoring of the patient in their real life, as opposed to coming into the doctor's office and reporting, "Okay, well last week I had pain here, but now it's a little bit better," et cetera. It's very hard to actually gather that data and process it, but now we can have the patient at home in their own circumstances. I see a future where we can reduce the number of visits that patients have for routine physician visits to do things like check labs, blood pressure, their level of activity, how they're walking, how even on the fly data entry of their satisfaction and pain control, et cetera.

All of that will really inform us in our clinical trials as to what the level of interference, not just the therapy is having, but the trial itself. There are many phase I studies where the patients are coming in for PKs and serial EKGs, and they're spending a lot of time in the hospital. And to the extent that we could bring those activities with remote EKG monitoring, and remote vital sign monitoring, a lot of the adoption of virtual healthcare that we needed to do during COVID for routine care, think about how to apply that to clinical trials so that there can be greater participation, less intrusiveness, time away from home, time away from either child or elder caregiving, time away from work. To be able to participate in a clinical trial, that's something I see in the next 5-10 years also expanding. It would be in everyone's interests. You get realtime data on the patient in their real lives, as opposed to the brick and mortar approach that we have right now.

Alicia Morgans: Absolutely. And you get the real patients, the population that really reflects the patients that we care for with this disease, rather than only those who have access to these certain areas, certain centers.

Michael Morris: I think all of us, we hand a patient a phase I or phase II consent form, they look at the treatment schedule of evaluations and they're like, "Not for me." And I think that to the extent that we can reduce the actual burden of the trial will mean greater acceptance of clinical trials.

For most of adult oncology, almost everybody says there's not enough clinical trials participation, but if you look at the treatment schedule or the schedule of study evaluations, I don't see any reduction in the workload that we're asking patients to do. So it's really appropriate only for a patient who has a certain amount of bandwidth in their lives that they can come in either daily or weekly for the first couple of months of being on a therapy. So I think if we really do want more early trial participation, let's use some of the technology that we have actually been rolling open, and what used to be a, "No it's impossible," quickly became during COVID, "Oh, absolutely. It's necessary. We can't actually function without those." If we keep that attitude up, that adoption of these new ways of practicing medicine or doing clinical trials as a necessity, not as a choice, I think we could get there.

Alicia Morgans: That's really exciting. I have really enjoyed this conversation, and I want to give you the opportunity to just give a final message on the arc of prostate cancer research progress. What is your message, Dr. Morris?

Michael Morris: Well, I think that if I were to see it from a structural standpoint, I do think it needs a multi-modality framework in terms of stakeholders. There's a role for industry sponsored studies, and there's also a role for government sponsored studies. As you know, I've saddled that divide for quite a bit of time, and I think it's really important that both be equally funded. There are some questions that industry can't answer, and there are others that a publicly funded entity like the NCI can't answer.

But there's an awful lot more than we could do than we do do, and I think that if you look at the yield of publicly funded research, it's been pretty good. Whether that's US or XUS, and in fact, I think we could really learn from many of the European trials, how efficiently they've been conducted, how successful they are in terms of yielding results. We have a lot to learn on that front.

But on the other hand from my perspective, we've done pretty well as a field, at least for my 25 years of involvement in it, and I'd say we're in a better place now than I've ever seen us as a community, and in terms of the scientific results that we're yielding certainly. We all should appreciate the efforts that everybody puts into this, and whether it's in the lab or in the clinic, the research administrators, the nurses, the patients. I think that everyone has really come a long way, and we're in a better place than we've ever been.

Alicia Morgans: Well, on that wonderfully positive and realistic note, I just want to thank you so much for your time. I agree and am so excited to see the continued evolution of the field and the progress, because I really feel like we're still on the upward trajectory of this arc. And until prostate cancer is cured and we take away all suffering from this disease, we will continue to have a job to do. So thank you so much for your time.

Michael Morris: Thank you, Alicia.