Matt Cooperberg: Good morning. I'm Matt Cooperberg. It's a pleasure to welcome you to another installment of in an person, a clinically localized center of excellence lecture series for UroToday. It is a real pleasure today to introduce two of the leading lights among the Young Turks in prostate cancer research focusing on disparities. I'm joined by Dr. Yaw Nyame from University of Washington, Fred Hutch Cancer Center, and Sam Washington with me at the Helen Diller Family Comprehensive Cancer Center at UCSF. Welcome to you both.

Yaw Nyame: Thank you.

Matt Cooperberg: So we're going to talk a little bit today about prostate cancer disparities, and there's obviously a ton of talk about this topic out there in the world, in the literature. And I think there's a lot of noise, and hard to find the real signals. And one of the reasons I've been particularly excited to talk to you both is I think both of you have a really wonderful sort of broader perspective on the problem. There tends to be a lot of what I find reductionist research out there. Well, it's got to be this one thing or this one thing, and it's obviously a complex problem to both elucidate and ultimately to solve. So I just want to start there, actually with what both of your takes are on the state of disparities research for prostate cancer, where we are, and some of the near term and midterm possible areas for improvement. Why don't we start with you?

Yaw Nyame: Yeah, that's a loaded question.

Matt Cooperberg: It is, of course.

Yaw Nyame: I think for a long time, the way that we viewed disparities or inequities in health was really framed around just the individual, as you sort of stated. And I think because we are scientists, we always think at this micro level about problems. And so what is it unique about you that maybe is inherited or some very unique risk factor that you've exposed yourself to?

And I think that even as an investigator myself, I could fall prey to that in the way that I thought about the problem. I think in the last five to 10 years, there have been a lot of leaders in inequity research, not urologists that have really framed the problem in the greater context that it exists in. And I think part of what my research team, and I know Dr. Washington's been doing the same thing, has been thinking about it from a more encompassing and broader perspective, thinking about it as if the patient is at the center of the problem, what are the things that are external that are surrounding them that might be contributing to the outcomes? And so those things are going to be health factors, social factors, structural factors.

Matt Cooperberg: Yeah.

Samuel Washington: I think it's exciting where we're at now. Because we have a roadmap from others outside of urology, who've really dived deeper into exploring drivers of disparities in framing this in a multi-level framework. So you have the individual, as Dr. Nyame mentioned, you have the local, state, government, historical lenses as well. So when you start to tease out these different levels, then you start to identify actionable targets. And that's what allows us to move from describing things as we have with one simple factor adjusting for everything else, providing a broader context. So I think short term, our goals really are, and I think the two of us and others are working towards this, is reframing how we examine disparities and how we discuss them. And then longer term would be how do we design interventions or take action in a way that incorporates what we know about the different levels, including our role as providers in some of these levels.

Matt Cooperberg: So let's talk about some of these factors, maybe in a little more detail. There's a framework I read years ago that I really sort of like about this three-phase disparities research concept. Phase one is identifying that a disparity exists. Phase two is understanding why it exists, and phase three is fixing it. And it feels like we saw phase one maybe decades ago, or at least we've had broader recognition in recent years, but I don't know how much progress we've made in phase two.

So of the multiple punitive factors or possible factors, genetics, environmental exposures, stressors, structural inequities, access to healthcare, and others, neighborhood factors. Where do you think, and it's a difficult question, I know, but do you think we're getting any closer to a sense of proportionate importance of these different factors? And obviously, some of them are modifiable, some are not, but in terms of both what the most important factors are and what the most actionable might be? Which I know is a hard question, but.

Yaw Nyame: Maybe I'll start.

Matt Cooperberg: Yeah, yeah, please.

Yaw Nyame: So my feeling is we have a pretty good understanding of the why. What we lack is a understanding of the why at a detailed enough level that we can create sustainable intervention and action. So prostate cancer disparities and equities are a bit complicated. And I think people don't really appreciate the nuance because on one hand you have a disparity or inequity in incidence. And if you look at prostate cancer, for the most part, the biggest risk factor that we can pretty consistently associate with disease incidence are going to be age and then family history. And when we talk about family history, now we're getting into genetics.

But one of the things that when I say that we lack the detail is when you think about the broader context, structural determinants of equity and health, we hear the term structural racism. Well, what does that mean? Right? Well, that can mean environmental racism. And every few years, there's a publication that'll point to the fact that a community that is exposed to a pretty significant amount of air pollutants or water pollutants have this abnormal risk of cancers.

Well, when I say we lack the level of details, we don't have a data source to dive into and try to understand these finer points. Even though I think from a broader perspective, we see where these communities live. We know the history of redlining. We understand what the environmental, the structural, and the social risk factors that may impact incidence is. But I think with the lack of data, it's hard to have this argument with someone who says, "Well, let me tell you about these family of genes that increase your risk," right? And that's a separate issue completely from the treatment-related inequities and the outcomes as far as mortality goes.

Matt Cooperberg: How much do you think the genes weigh into it? You and I were at one of these meetings. I think it was CisNet talking about the international perspective and the mortality rates in the Caribbean and other countries with high West African genetic ancestry, where you do see these really off-the-chart mortality rates, disproportionate to even other low development index countries. I mean, does that tell us a signal about the relative importance of genetics, or do you think most of the story is environmental?

Yaw Nyame: Well...

Matt Cooperberg: And I, environmental, I'm speaking, everything that is not genetic.

Yaw Nyame: Well, I think that again, we have to be careful. Environmental is just one example.

Matt Cooperberg: No, environmental not [inaudible]...

Yaw Nyame: But maybe the structural and social, I mean, we need to tease apart a little bit better. I think if you look at the data, our polygenic risk scores, multi-ancestral polygenic risk scores are really strongly predict disease risk. What's interesting is a conflicting data that exists on the contribution of genetics maybe in, let's say Sub-Saharan, West Africa. I can find studies that say men who are from Ghana and Nigeria have a much higher risk of prostate cancer than men here in the United States, or similar risk.

But those studies have some limitations. And I can find studies, for instance, I can think of an autopsy study that was published within the last few years that show that maybe the rate of incident prostate cancer in men in West Africa is much lower. So we have a data problem. One of the things that you mentioned earlier that's really exciting for me as a young investigator, and I talk to my good friend and colleague here about this all the time, is there's no shortage of RFAs that are coming through requesting, giving opportunities for funding to do this kind of work. And to build new resources, to create these answers is going to require that level of support. And I think we're both really thankful for these opportunities to get funding.

Matt Cooperberg: For sure. Speaking of that, maybe talk a little bit about the neighborhood work that you've been doing with the Dream Lab and getting down to some of the structural inequities at a granular level. Do you think we're at a granular enough level with the data that you have access to or are there more resources needed?

Samuel Washington: I would say much more resources are needed. We're getting there. So I think that the work done by our colleagues, Dr. Gomez, Dr. Chang and others at UCSF looking at neighborhood-level factors really drive home the importance of context. And that context is the environment or social environment in which people live and receive care. That's the environment in which we do our work, where we provide treatments. So that becomes an easy area, relatively easy area for action if we can identify appropriate targets. And that's where we need the granular data.

But I think what that also lends itself to readily is an understanding that prostate cancer disparities are a subset of the broader issue. So when you start to understand how disparities are being perpetuated within that social environmental context, you understand that a subset of that is prostate. A subset is breast. A subset is bladder and other cancers. That provides you universal, actionable targets if you can identify those with granular enough data. So hopefully we will get there. I do not think we are there yet, but, yeah.

Matt Cooperberg: So which pieces are actionable? Obviously fix redlining is not something that we can really do as urologists. So where are the points where we actually have influence potentially as academics, as clinical urologists? Where do you think we can have the greatest impact as a specialty?

Yaw Nyame: I can tell you what our approach has been. Right? And I think that one of the exciting things is that there are many investigators of all levels that are taking different approaches to this. When I came to the University of Washington, I wanted to do high throughput, genomic and biologic research. That's sort of what I knew. My dad's a biochemist felt familiar and I wanted to do biomarker work. And I quickly realized that the resource in the form of patients just didn't exist. And it's hard to compare hundreds of men to tens of men and say anything meaningful.

That also is piggybacked by the fact that I started to realize that the need is far less than biomarker discovery and more in just the support around diagnosis and treatment that men need.

Our approach has been to come into it somewhat agnostic. I mean, I think for a long time, clinicians and researchers, the smart people get in the room and they say, "This is what people need." And that's familiar. It's easy. It's much easier to do, but oftentimes it's not effective. And I use my experience from business school to think about this. If I was going to open a coffee stand, I wouldn't just sit in a room with my investors and say, "Hey, let's open a coffee stand. This is what it's going to look like. This is what we're going to do." We would talk to people on the streets.

And so we are doing that in a very intentional community-facing way with a series of qualitative methods, which is all new to me. So now we're doing semi-structured patient interviews. We're thinking about focus groups, we're using surveys, and we're doing a lot of community work. And one of the things that we started in the last year and a half was an organization called the Black and African Descent Collaborative for Prostate Cancer Action. The acronym is BACPAC. And it's not meant to be an advocacy network. Plenty of those do exist, great advocacy networks, whether they're FEN or ZERO or PCF.

But what it is intended to do is be a research instrument for community members and to help galvanize, educate, support prioritization and the development of interventions and research for Black men in their communities. And I think that kind of approach gives us a better opportunity, not only to be successful in our outcomes when we design these studies, but it also helps us bring people to the table. It helps build those relationships. When you have an intervention and an approach that is collaborative, that is supportive, you have buy-in, you have ownership, and ultimately you have a greater chance for success. And so that is really where we put, or I should say I've put all of my chips into that basket. And I'm a big believer now.

Matt Cooperberg: Terrific. In San Francisco, we have [inaudible]. Do you want to talk about that a little bit?

Samuel Washington: Yeah. So within UCSF thankfully, there's been an intentional movement towards community partnership. So partnering programs through community, with community leaders focused in specific domains that impact San Francisco proper. San Francisco Cancer Initiative is one of those. And one of those five arms is the Prostate Cancer Action Network. So these are community leaders partnered with UCSF rather than us from UCSF coming out into the community, but really understanding how can we empower and educate men so that they feel informed about their decisions and what the options even are.

The other aspect of that is the Office of Community Engagement Outreach led by Dr. Kim Rhodes, UCSF as well, an intentional department and division created to foster partnerships from the ground up. So research projects are not developed by the researcher and then taken out of the walls of UCSF, but developed with the community from ground zero.

And I think that provides a way for the community to be engaged, but us as urologists, that may not always be the opportunity. So for us at UCSF, we're leveraging those partnerships more. But I think within urology, in terms of actionable targets, it's really understanding what our own practice is. So understanding what barriers our patients may have and understand that those may be different than patients across the country. And that also means that we have to take a hard self-look at our practice patterns. So understanding how practice in San Francisco differs from practice in Houston, where I grew up, lends itself well to a risk profile that varies based on where you are and what social environmental context you live in. And I think understanding that profile and acknowledging that it exists and that it differs are the real things that will drive us forward. But I think we have to first, everyone has to acknowledge it and start to look.

Matt Cooperberg: For which we need data.

Samuel Washington: Yes, exactly.

Yaw Nyame: And I think in line with that, there's this idea that, okay, we're going to create this one size fits all solution for this problem. And certainly, there are some issues that a one size fits all solution will work for. Supportive services, if we had opportunity to have federal funds to support men through their cancer treatment, for instance, maybe that would work, right, because we know that is a pressure point. But to Sam's point, you have to think both at a macro level and at a micro level simultaneously. And that's the challenge. That's very expensive. It's very time-consuming. In BACPAC, we're finding ourselves setting up Zooms with people on the East Coast. And it's, just even as a team based out of the West Coast, the logistics of doing this as a small unit is really challenging, but it's also very rewarding.

And sometimes you hear two men from very different communities echo the same stories, or sometimes provide some complementary information that's important to think about. For instance, we have a member of our team talk about the need for interpretation services, because there's a big immigrant population in the Puget Sound area, in designing a study. And that light bulb went off to think about, well, how are we going to serve our Somalian and Eritrean population? So this is such a complex issue. And when it's distilled down to, well, we just need to get everyone treatment, it's difficult for me because I think that's not acknowledging how challenging this problem really is.

Samuel Washington: And I think also people will often say, "Well, we just need to get everyone insurance." And we know that even within the VA system, which I more commonly call an equal insurance system rather than equal access, we're seeing variations of conservative management even within localized prostate cancer. So that tells me that, are we having the same access even within a healthcare system where cost and insurance coverage is not as large of an issue? And I think we really need to drive home that every area, there's an opportunity for further investigation and more granular data so we can understand that.

Matt Cooperberg: How much of the short-term progress do you think we can make by focusing on screening? I mean, this has been a big plank for [inaudible], and drawing largely on your work with Ruth Etzioni and the CisNet group suggesting that the disease trajectory is actually not that radically different between Black and White men, but starts maybe five years earlier, give or take if I'm interpreting the latest paper accurately. I mean, do you think, how much mileage do you think we can get out of really focusing heavily on better screening, better access to screening?

Yaw Nyame: Well, when we published that data, one of the things that I wanted to make sure that our group did a really great job, and because it was just such a great project led by Roman Gulati, and Dr. Ruth Etzioni that we kept our perspective correct, that this was in an idealized situation, right? And so we know in an idealized situation that if we screen earlier, let's say age 40 or 45 as the study used, we can reduce mortality. And if we're smart about how we screen, if we don't screen indefinitely and we stop when the risk is proven to be low, it's age 70, or 65, you can definitely do that without introducing a lot of additional harm.

But we interviewed about 35 Black men as part of our first study supported by BACPAC. And what you hear from those men is a very different story. Those men know their risk. They understand that PSA screening may benefit them. There are maybe some personal health knowledge gaps, but they know that they probably should be screened. And they go to their primary care physician and they say, "Doc, what do you think about PSA testing?" And what do you think they say? "Well, I don't think it helps very much. There might be, that might not benefit you. You might end up getting a biopsy you don't need, you might end up getting treatment that you don't need."

And some of those men said the only time that they could get a PSA test is when they finally switched their provider to a Black primary care physician who had a different view on their risk and was able to help them navigate that shared decision-making process, right? And so it's one thing to have a policy recommendation rooted in really high-quality data. It's another to create action so that you can actually realize that benefit. And so how close are we? I think even if we change the recommendation, there is inertia in the community among primary care physicians about really what the benefit of PSA screening. That is a bigger topic that we could probably spend another recording session doing. And that's difficult.

Matt Cooperberg: It is difficult. I will say it is possible. And it is, it's always been my view, one of the things where we really can have an impact as urologists is educating and influencing the primary care, right, folks who ultimately do make these decisions. And we have actually had a lot of success at UCSF through [inaudible] and engaging with the primary docs. And I have to show you the latest data, Sam. We have, through a series of CMEs and engagement, and now a health maintenance banner that we've got plugged into our Epic environment, there is actually encouragement explicitly for shared decision-making. And the latest data are actually that the screening practices are actually much more optimized now for Black men than for everybody else. So earlier age and less screening as men get older. It's actually that curve, and only that curve for the Black men and not for anybody else really looks like what it, starting to look like what it should look like. The rates are still too low, but we are making progress through engagement, which is...

Yaw Nyame: Really reassuring.

Matt Cooperberg: We can get there, but it's work. It was a two-year conversation.

Samuel Washington: And I think we have to frame it in that if people are getting screened, they are seeing urologists. And then we need to make sure that they're getting guideline-concordant care. So I always have to apologize for being critical of our own field, but we know that the rates of guideline-concordant care are not the same across different groups and across different areas of the country. So we have to know that if we have a bolus of patients coming in that are now being screened, that they are getting the appropriate care and getting us closer to that ideal model where one person screened, diagnosed, and getting appropriate treatment for better outcomes.

Yaw Nyame: And this is an important point. Yeah, we've studied this, and have a manuscript out that essentially asks the question, how much of this is something that has to do with the individual's health risk and how much of this is an issue of healthcare delivery? And this is work led by Noah Hammarlund, who's a PhD now at the University of Florida, who was at UW with us. And he used this economic modeling technique, statistic technique, called the Oaxaca blinder technique. And what he showed was if you take the model, which is a care delivery model for white men, and you applied it to the health characteristics of Black men, that their treatment rates suddenly normalized to those of white men. And in fact, there are slightly higher, not significantly so, but you have same treatment.

The flaw of our study is that we don't have that granularity. And that flaw that exists because there's no granularity in the data that we're using, but it tells you a lot about what is driving, what Sam calls, guideline-concordant care. I mean, what are you offering? How are you counseling? How are you supporting a man with a localized prostate cancer diagnosis that is Black? And I will tell you from now as a junior faculty, who's taking care of patients, you realize, man, when that bladder cancer or kidney cancer patients is new, you come in and you say, "This is your option." Then you see a prostate cancer. And you're like, "I can't, 30 minutes is not enough." I need an hour slot, right? Because it's such a complicated decision. And so you can understand that if someone is receiving their care where they don't have access to experts like yourself, Sam, if they don't have the resources and the time, that it's easy for someone to fall off of that train and not get the treatment that they need.

Samuel Washington: I think one of the large takeaways from this is that there are efforts moving forward, but we're changing the paradigm in how we explore them. So I think up till now, the last 20, 30 years we've been using national data. And we're understanding now that you need more granular data, down to the neighborhood or even deeper. But even with that granular data, you're still missing context. And that's only gained through qualitative studies. So I think the incorporation of mixed methodology is something that's new to urology, but well established outside. And I think that provides a much more rich and comprehensive understanding of disparities. So I'd like to see that move even more so into urology. And I think that's exciting to see what will happen in the next few years within disparities. And I frame it that way, because again, a lot of these things we will find are not necessarily unique to prostate cancer, but our understanding will help those men diagnosed with prostate cancer as well.

Matt Cooperberg: Wonderful. We could continue this conversation for hours, I think. And I look forward to having you both back to really track progress in this complex, critically important, and rapidly evolving subfield within prostate cancer research. So thank you both for coming, and thanks for [inaudible] talk again soon.

Yaw Nyame: Thank you.