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Matthew Cooperberg: Hi, I'm Matt Cooperberg. Welcome to another edition of the UroToday Localized Prostate Cancer Center of Excellence, coming live from the AUA 2023 in Chicago. It's a great pleasure to be joined today by Dr. Isla Garraway, who is professor of urology at UCLA and the West LA VA, and has been a major driving force in nationwide genomic programs through the VA to try to get a better sense of what we can learn about prostate cancer through this unique, exceptionally diverse population. So welcome.

Isla Garraway: Thank you.

Matthew Cooperberg: Thank you for joining us. To start with, for those that are not familiar with the VA, I want you to just tell us a little bit about what makes the VA unique from the prostate cancer standpoint and some of the programs that National Precision Oncology Program (NPOP) and these other agencies have been driving for us.

Isla Garraway: Yeah, no, absolutely. And it's a great question, and I think one of the really unique things about the VA is really the diversity of the population. I think you mentioned that already, but it's an amazingly diverse population, not only racial ethnic diversity, but geographic obviously, because there's VAs all across the country, coast to coast, northwest, southeast, so we can understand the impact of the geography on veterans in terms of their overall health and their treatment and their access to care. So we have veterans who live in, obviously in urban settings, and we have those who live in really far rural settings. So we need to be able to reach all of them and understand how the disease impacts all of them. So that's really part of our work and what makes the VA so unique.

Matthew Cooperberg: And what have we've been learning recently about what is unique for the veterans? There is obviously issues of geographic access and diversity and all this, but are there things that we're learning that there's really unique biology due to Agent Orange and these sorts of exposures, for example?

Isla Garraway: Yeah, for sure. I mean, I think that we are still learning from the veterans. So first of all, the access to care is a huge issue for veterans. So one of the things that we have recently learned is that some of the disparities that we find in prostate cancer, for example, some of the racial ethnic disparities, we don't see in the VA population. So the relatively open access VA healthcare system is really mitigating a lot of these disparities that are so prevalent outside VA. And that's amazing. That's wonderful. However, if we do still see some key disparities, so for example, although we don't see a lot of disparities in terms of outcome, once men are diagnosed with prostate cancer and are being treated or cared for in the VA system, we still see a large difference in terms of the incidence of prostate cancer. So similar to what we see in non-veterans, black or African-American individuals have a significantly higher incidence of prostate cancer in the VA system.

Matthew Cooperberg: And of course, VA's been described as equal insurance, but not necessarily equal access if there are issues of transportation, time off work, all these sorts of things.

Isla Garraway: Absolutely, yes, yes.

Matthew Cooperberg: So how much do you think the incidence, in the VA specifically, reflects access issues versus inherent biologic risk due to either genetics or adverse environmental exposures?

Isla Garraway: Yeah, so that's one area that we're really interested in, I think not only us, a lot of people in the VA are really interested in studying and we are studying right now. So for example, one of the ways you can look at that is to look at kind of neighborhood level factors, so which you can look at kind of aggregate measures of vulnerability or disparity of the neighborhood. And then you can also look at kind of individual level factors like individual income or wealth assessments, which they actually do in the VA. They do what's called means testing, up until recently. I think they've kind of stopped doing that now, but you can look at what the veterans have reported as their income. So when you look at those individual measures, it does still seem like those weigh in terms of the outcome.

So veterans who report lower income or no income, they definitely seem to have worse outcomes than those who have better incomes. On the other hand, the neighborhood level differences really don't seem to matter anymore. And that's a real stark contrast for non-veterans. So non-veterans, if you look at, for example, the Area Deprivation Index, as the Area Deprivation Index goes higher, which means a more deprived neighborhood, the overall survival goes way down. But in the VA, that does not happen. It does not seem to happen so far, at least in the studies that we've started to look at.

Matthew Cooperberg: Which is a testament, I think, to the VA working as an actual integrated healthcare system in the United States.

Isla Garraway: Exactly, exactly. But you're right. So those individual measures which might reflect the ability to access transportation, for example, or get time off work, those still impact, but the overall kind of just access to care, which might be reflected more in that neighborhood level value metric, really not... alleviated, eliminated by VA care.

Matthew Cooperberg: So what about at the biologic level? Maybe talk a little bit about the MVP and some of the work-

Isla Garraway: Oh yeah, for sure. Yeah. Right. Yeah, yeah.

Matthew Cooperberg: ... that you're doing, you're leading in somatic testing for vets with prostate cancer?

Isla Garraway: Sure. Well, as we know, prostate cancer is one of the most hereditary cancers. So that means, at the genetic level, there are factors that can be passed down from generation to generation, but we don't really know what all those factors are. I mean, there's some that are very clear, that have a very clear link, but then there are many other more common genetic alterations as we call them, that when you put them all together, they translate into a higher risk. But we're still understanding what the whole mix is that leads to these higher risk. And the VA provides a really great population to study that in, because again, the diversity so that you can look across different race, ethnicities, ancestries to see what the genetics look like and how they might be associated with prostate cancer risk.

And one of the ways that you can do that in the VA is because they have what's called the Million Veterans Program. So they started a program back in about 2016, and their goal was to recruit a million veterans to give blood for genetic testing, not only to focus on prostate cancer, but across many different diseases. But that's allowed us to really look at the effects of different genetic alterations on prostate cancer risk. And so we're really taking advantage of that now, and we don't really know all the results yet, but it's definitely going to be interesting to see what that shows and really kind of look at the balance between what's coming from a genetic risk versus the access to care and other social determinants of health and risk factors for cancer that we know.

Matthew Cooperberg: Sure. Do you know how far up to the million mark they're getting?

Isla Garraway: They're close. They're really close. The last time I heard was around 850,000, but that was a little while ago, so they might be there already. Yeah, so it's definitely a lot of data. They haven't finished the genotyping, I don't think, on everyone, but definitely hundreds of thousands of veterans have already had that genetic testing done and tens of thousands with prostate cancer so we can see the effects.

Matthew Cooperberg: And maybe talk a bit about POPCaP, the [inaudible 00:06:42] spearheaded by PCF to-

Isla Garraway: Spearheaded by PCF, yeah. So yes, the Prostate Cancer Foundation formed a partnership with the Office of Research and Development in the VA, and the idea was to really make sure that veterans have access to precision oncology. So that was a huge undertaking because in order to have precision oncology and have specific medical treatments that are very targeted to your cancer, you have to first sequence that cancer. So there was a huge effort to make sure that veterans have sequencing. And so this has been amazing because we now have, baked into our guidelines, clear indications for sequencing, both sequencing the germline to see what is hereditary, but also sequencing that tumor in patients with metastatic disease. So basically any patient with metastatic disease is pretty much a candidate for sequencing. And then therefore, if there it's discovered that they have very specific alterations in their genome, that can be treated with medications that can target that, then they can have that access.

In addition, we've really increased the number of precision oncology clinical trials in the VA to make sure that veterans have access to those trials. And we've tried new things like we're in the process of opening up kind of tele-oncology clinical trials like using telemedicine so that we can really reach everyone where they are. They don't always have to necessarily come to a major VA to be able to have access to clinical trials.

Matthew Cooperberg: And what's next? What's on the horizon in that regard?

Isla Garraway: Oh, wow. Well, I think-

Matthew Cooperberg: There's always a lot.

Isla Garraway: Yes, there's always something more. I mean, I think really it's just moving forward on all cylinders in all those different areas to really improve equity and understand who is at the highest risk of developing prostate cancer, making sure we are doing screening and early detection appropriately in our VA population, especially as you mentioned earlier, accounting for our very special veteran population who've had exposures, who've had military exposures to different things. We really want to understand the impact of these different exposures that they've had. And so we're really interested in partnering with DOD and other entities to really quantitate those exposures and see what the impact is long-term.

Matthew Cooperberg: We do still have a bit of a gap between the screening, the exposure, and the metastatic disease in terms of how much we're able to profile veterans with localized disease.

Isla Garraway: For sure. Yes.

Matthew Cooperberg: Any progress on that front?

Isla Garraway: Yeah, I mean, it's definitely still needing to build that gap. I mean, there's so much we don't even understand about the biology of what these exposures are doing. And now the VA has really focused on this. They have really interesting quantitative measures and actually dashboards where you can look at in detail and actually even inform the veteran about their potential exposures based on where they were deployed. So it's an amazing... It's called the Individual Longitudinal Exposure Record or ILER, but the downside about that is it's post-9/11, so it's really doesn't cover veterans who were in the Vietnam War with Agent Orange exposure or even patients who might have had Camp Lejeune exposure. So we still are stuck really there in terms of being able to really quantitate the level of exposure other than really trying to line up with deployment records and things like that. But we're really trying to, again, trying to work with other entities and agencies to figure out how we might be able to better quantitate this and study these exposures and the impact on prostate cancer risk.

Matthew Cooperberg: Yeah, wonderful. Any sense so far in exposures in the new generation of veterans coming back from Iraq and Afghanistan? I've heard reports of these dioxin exposures through the burn fires-

Isla Garraway: Oh, right, yes. For sure, yeah. I mean, I think the particulate matter, the PM 2.5 from the burn pits and everything like that. There's also an interest in really understanding what's happening with the aviators because aviators in the cockpit and from their different exposures to jet fuel also appear to have an increased risk of cancer, in particular, prostate cancers. There's some early data suggesting that. So that's another real area of interest in terms of military exposures is understanding what their risks are and how to mitigate those risks.

Matthew Cooperberg: Yeah. Wonderful. Great. Anything else you'd like to share with us?

Isla Garraway: I think you've covered it.

Matthew Cooperberg: Thank you again so much for joining us. Thanks for your time.

Isla Garraway: All right. Thank you.

Matthew Cooperberg: And I really look forward to watching the next phases of the work evolve.

Isla Garraway: Perfect. Thank you.