Precision Oncology: The PCF - Veterans Affairs (VA) Initiative - Bruce Montgomery

April 1, 2019

Bruce Montgomery shares an update on the PCF - VA research Initiative on precision oncology in prostate cancer.  Prostate Cancer Foundation has provided a $50 million dollar contribution to this VA specific prostate cancer effort.  Bruce and Chuck Ryan discuss the developments to date and the future plans.  

Biographies:

Bruce Montgomery, MD Board-certified oncologist, clinical director of Genitourinary Oncology, Seattle Cancer Care Alliance, UW Medical Center, an affiliate member of Fred Hutchinson Cancer Research Center and a UW professor of Medicine, Oncology and Urology

Charles J. Ryan, MD is the B.J. Kennedy Chair in Clinical Medical Oncology at the University of Minnesota and Director of the Division of Hematology, Oncology and Transplantation.


Read the Full Video Transcript

Charles Ryan: Hello again from the Prostate Cancer Foundation, 25th anniversary retreat in Carlsbad, California. I'm delighted to be joined by my colleague and friend Bruce Montgomery to talk about the VA and its role in prostate cancer research. Bruce is a Professor of GU Medical Oncology at the Seattle Cancer Care Alliance and the University of Washington Medical Center. So welcome, Bruce, to PCF and tell us about what's going on at the VA right now.

Bruce Montgomery: Thanks for the opportunity. It is a pleasure to talk about this. So the Prostate Cancer Foundation has made a very substantial contribution to the VA specific prostate cancer effort. So they've committed $50,000,000 in prostate cancer-specific funding within the VA. The first step along that way is what's called our Centers of Excellence Network. So right now there are a total of seven centers, all of which are under the same umbrella. The whole idea behind the effort is to develop an approach to precision oncology and prostate cancer, which we hope to really have a model for many different systems.

The VA is the largest integrated healthcare system in the United States. So working in this system I think makes a lot of sense. So we're sequencing every man with metastatic prostate cancer. Every tissue we can find, circulating tumor DNA at every change in therapy. Then we have instituted multiple clinical trials within the VA specifically, and actually are funding men to travel from each center to a place that has a study specific to the mutation that is found for them. So those are, I think, differences from what is the standard right now in the VA and provides real opportunities for veterans that weren't there before.

Charles Ryan: So just to clarify, a veteran can be sequenced, he's got prostate cancer, he can get sequenced, if he's found to have a mutation, let's say CDK12, and he's at the Minneapolis VA and there's not a trial there for CDK12 mutation, he could go to the Seattle VA.

Bruce Montgomery: That's the general idea. Right now, the support is mostly from within the network. So that somebody who is in, for example, Los Angeles, if they had a CDK12 and we had the study open in Seattle, that travel would be supported. The hope is that this venture would grow to the point that yes. I mean, the idea here is that each of these centers will actually act in this hub and spoke manner. That everybody within the VISN will be eligible for care there and therefore to whatever site in the country is available, depending on what mutation we're talking about. Again, this focus is really specific to precision oncology.

Charles Ryan: So for those who aren't familiar, the VISN is basically a regional system of the VA, a VA hospital.

Bruce Montgomery: Exactly. It's a catchment area for each of the systems. There is usually a tertiary care center within each one. And then multiple other medical centers which communicate with the tertiary center and we act in concert to some degree. The whole idea behind this effort is to provide precision oncology to anybody in any of those different centers within the catchment of any of these Centers of Excellence.

Charles Ryan: Great. So you said that there are $50,000,000 going into this. Is this just for medical oncology? Or are we talking about efforts in urology, and prevention, and basic science?

Bruce Montgomery: That's a great point. So the money, we certainly have not put $50,000,000 into this network yet. It has come out also in the form of what are called valor awards, which are PCF challenge awards that are put out specifically to VA investigators. So a number of them have been funded already and many more will be over the next five years. So it encompasses all different levels of research, clinical sequencing, and basic science within the VA.

Charles Ryan: So what are the unique challenges that veterans with prostate cancer may face, either in terms of biologically if there are any or care wise or...

Bruce Montgomery: That's a good point. I think there are many aspects of prostate cancer within the VA, which are relatively unique. For example, there is a specific potential link between agent orange exposure and prostate cancer. And a number of veterans who served in a position in which they were exposed to agent orange, we think are at much higher risk for having developed prostate cancer. That is one specific aspect. The second part is that the VA as a whole actually does extremely well in terms of many aspects of care. Primary care, in particular, we perform actually better than many primary care systems, not just manage, but even smaller practices.

Oncology has been a little spotty in terms of access to clinical trials, and we, not just through the Prostate Cancer Foundation network, but actually the VA as a whole under Rachel Ramoni, who's the current head of R&D, is making a very focused effort to bring more clinical trials in prostate cancer specifically. We're sort of the poster child, if you will, of that effort. I think the biology of prostate cancer isn't necessarily different. There are obviously different ethnicities and different healthcare systems in the United States. The agent orange part is the specific part. We also would say that we've learned over the last several years that people have inherited a propensity to get prostate cancer, what are called germline abnormalities. Veterans tend to be older men, even older than the average man with prostate cancer in the United States, so they're actually more likely to be able to have, finding, for example, a germline abnormality be beneficial to the rest of their family because their kids are grown. You're going to be able to actually have them undergo surveillance that's appropriate. I mean those are obviously offshoots of that. Not specific to the biology in veterans, but I think that's one aspect of it.

Charles Ryan: Let me focus a little bit on the clinical trials that you're offering. Are you seeing industry trials that I might be able to open at my institution or even could be open in a community center? Are they now open at VA centers or are you having specific VA trials that are-

Bruce Montgomery: So both. So actually there are a number of studies that are, within right now just the network, mostly focused on homologous recombination deficiency. We are collaborating with a couple of spores to do those studies, but we're going to be the primary implementation sites for those. We are also participating in TRITON2 and 3 for example, the VA was one of the biggest accruers to profound, which was another PARP inhibitor study obviously just closed recently. Phase III very large study of the VA did extremely well in recruiting patients. So we are engaging with industry to bring more studies into the VA, but we're also trying to develop within our network and the VA specifically studies that otherwise wouldn't be supported by industry. Not that this wouldn't be a good idea, but obviously there are different reasons for studies to be done in different places.

Charles Ryan: Well you and I are both oncologists. We're both professors at medical schools and we both have faced the challenge and have the tremendous opportunity of helping junior faculty develop their careers and to launch the careers of researchers. My understanding is the VA has become a place now where junior faculty can seek career development awards and that this is becoming a really... It's always been a great nurturing environment for education and clinical care, but I think now we're seeing the VA's become a great place to do research.

Bruce Montgomery: Absolutely, and I think back to what you have said, I think many of us trained in VAs along the way. That I think has been a very instructive experience for many of us, and as a result, many of us feel very strongly about caring for veterans. I think the idea that junior faculty can come up through, for example, the VA is a very viable career trajectory and actually specifically, the prostate cancer foundation is supporting young investigator awards that are VA-specific with that in mind. With seeding the VA in a way that it doesn't just mean that people will go through the VA and graduate to other medical centers, but the idea being that as many of us have, we share affiliations between the academic side of the VA, which benefits everybody. And I think that that's really the model for the future that I think we're trying to develop.

Charles Ryan: Well, I think these the valor system, and the clinical trials, and these relationships that have developed with industry essentially offer opportunities at the VA that weren't there before and were the missing link between why somebody would maybe not want to spend their senior academic career there. It's really a great thing to see this developed. Who else is involved with this? I know you're one of the co-directors of this program and what's the structure of the leadership.

Bruce Montgomery: Right now the... Again, we have seven centers, Matt Rettig who's at UCLA and the Los Angeles VA are helping to move the various pieces around that make this happen. The other sites that are involved are Ann Arbor, Chicago, Manhattan, and the Bronx, and very recently Philadelphia. We actually anticipate that in the next year or two we may be up to 12 to 15 centers.

Charles Ryan: What would somebody who's listening to you talk today, who is out working at a VA and wants to get involved, how should they do it?

Bruce Montgomery: Just let us know that you're interested and you feel as though you have the infrastructure to at least think about getting that in place. I think the idea of the network is that we also provide a lot of support to make this happen. Back to something that I didn't answer earlier. I think yes, right now the main focus is in the area that the Prostate Cancer Foundation, in general, has been most focused on, men dealing with metastatic disease. But I don't think there's any question that moving precision oncology earlier in the disease trajectory so that we're looking for things like homologous recombination deficiency or other molecular points of leverage shouldn't really be brought to bear at much earlier stages of the disease.

Actually I think the VA is a wonderful place for that because it's the number one disease. We actually have a much higher percentage of men with high-risk disease who present in that way. And so I think the potential benefits to them through this program will, I think, come to be clear in the next several years.

Charles Ryan: Great. Well, I think it's very exciting. I mean, as a division director myself now to be able to work with our VA colleagues and to see it be an avenue for career development for junior faculty, to see it be an avenue... As a clinical investigator, I'm involved in the TRITON studies to see that the VA's are accruing, that's very gratifying and I really want to applaud you, and Mark, and the PCF for their leadership and bringing this to happen to veterans and VA hospitals across the country.

Bruce Montgomery: Thank you so much.

Charles Ryan: Thank you for coming.

Bruce Montgomery: I really appreciate the opportunity to talk about it, and anytime in the future.

Charles Ryan: Our pleasure.

Bruce Montgomery: Thank you.