Charles Ryan: As we've made progress in the fight against prostate cancer and develop new therapies that improve the lives of men with this disease, allow them to live longer and better. Attention to disparities in how those treatments are implemented, and how care is received by patients, has become more important.

The Prostate Cancer Foundation has been paying attention to this issue, and funding research on disparities in prostate cancer care delivery, outcomes and biology, for a decade now. I'm delighted to be joined today by one of our original pioneers in this area, Dr. Kosj Yamoah, who is now the Chair of the Department of Radiation Oncology at the Moffitt Cancer Center in Tampa, Florida. But before that, he was a young investigator, studying disparities in prostate cancer. Kosj, thank you so much for joining me today to talk about your work. Let's go back to when you were first awarded your Young Investigator Award. What were the aims? What were the goals and how's the progress coming?

Kosj Yamoah: And Chuck, thank you for having me here. This is an incredible opportunity to get to look at the journey, and reflect on how we've come this far, and how we can even do more. And so the original concept for the Young Investigator Award, specifically looking at the disparities, was to understand a couple of things. Prostate cancer's disparity landscape really originates from incidence all the way through death, through metastasis to death. And in order to understand the different components of that, the goal was to first see if there are any biological differences that could allow us to exploit those differences for therapeutic benefits.

Separate from that, was going to be the mission to understand how the disease actually of caring differently between those patient populations, particularly with their understanding that the incidence rates are higher in men of African origins, all things being equal. And in order to really understand that, we thought we could actually use a biological approach and adapt to that with a lot of the access and basically more of a epidemiologic approach. And so their initial goal was to look at the biological factors that impact aggressive disease and also increase disease prevalence and then go back into why those could inform us as to why the disease of caring much sooner.

Charles Ryan: So you really started with biology.

Kosj Yamoah: Yes.

Charles Ryan: Your hypothesis was there's a biological difference based on race and that this is going to lead to disparities throughout the spectrum of the disease.

Kosj Yamoah: Right. And the concept there when we think about that was that prostate cancer is a biological process and what causes prostate cancer could be multifactorial. And that in itself is a field of investigation. And whether it's a built environment or exposures or some form of genomic differences, ultimately affects cellular function. And so that was almost like the final point where we wanted to see what biological care process is being altered, that that could then lead us down the paths of ideology, which could lead us into several different avenues of research.

As of 2022, our current state of thinking with prostate cancer health disparities is that knowing that prostate cancer is a biological process, what we wanted to look at is the intersection of all the factors that lead to prostate cancer and how there is a difference in the biological processes that ultimately leads to difference in overall mortality. And the way we decided design this was to take a look at the cellular level on the tissue level and understand which pathways or which molecular subtype might be co-opted more in one subpopulation than the other, and begin to understand how these subtypes influence disease process in prostate cancer.

Charles Ryan: So the more I study prostate cancer, the more I am humbled by the fact that there are diverse biological processes. And I clearly see that when we talk about nutrition and we talk about environmental effects, there are clearly groups of people within the population who have a disease that's driven or altered by their nutritional status, their metabolic status, their background, environmental status.

Could you speak to how your work on the genetics of disparities and the biology of disparities interact with those variables? Metabolic, environmental, social?

Kosj Yamoah: Thank you for that question. When we think about prostate cancer, we need to understand that this is a multifactorial disease, that the causes of prostate cancer carrying in specific lifetime is often triggered by different input from nutritional status over decades, exposures, stress, metabolism, and in most instances, the genetics is actually a small component of the disparity. And it really goes down to how these other factors influences either epigenomic factors or cellular processes that are triggered by difference in environmental stimuli. And in order to really understand prostate cancer disparities, it's very important to have the right population and ask the right question. In regards to disparities globally, we observe that incidence, that's the disease or carrying in men of African origin is a global problem. It doesn't matter where you look in Africa and the Caribbean, in the UK, in the U.S., doesn't matter where you look, men of African origin do get prostate cancer more often and at a younger age.

So that begins to let us take a pause and say, why is that? These are populations that are separated by several years, generations, centuries, and yet we still see a common increased or occurrence of a disease. But that's also an opportunity to make impact. But perhaps if we study prostate cancer in all the multiple groups of patients or people in different continents, we can begin to very quickly understand again, these triggers of disease process within the prostate gland and perhaps give us clues to how to better treat the disease. So studying prostate cancer globally is imperative.

Charles Ryan: In addition to your work at Moffitt Cancer Center, you are also the program director for the John and Daria Barry Veterans Administration, Prostate Cancer Center of Excellence. Tell us a little bit about the work that's going on in the VA with regards to disparities and your involvement in that.

Kosj Yamoah: PCF's mission to address disparities globally starts from the U.S., our Veteran Healthcare Administration and the Veteran Healthcare Network is one of the few places in the United States where access to care is near equal, that men with prostate cancer or veterans do not have to pay for their care and can access it. So that gives us an opportunity to address disparities in a very unique way that we could not otherwise do in other healthcare systems within the U.S. And so PCF partnered with the VA and set up these centers of excellence for precision oncology and happened to one of the leaders in that field when it comes to the work in disparities. And I can already say the entire group, including several investigators across the United States, are already begin to understand very clear patterns of prostate cancer disparities that yes, indeed the incidence is different, but the good news is treatment response is identical, if not even better for some types of treatment in men of African origin.

And I say this is good news because for the first time we are begin to realize that we can address prostate cancer on two fronts. We can address the access issue, which would take care of a lot of the poor outcomes we see in men of African origin, but also hone in onto where disparity is actually coming from when it comes to the fact that men of African origin are getting the disease more. And the VA network has created a very important environment where we can really study this and make a difference in the field of prostate cancer health disparities.

Charles Ryan: Africa is a massive continent with very diverse populations. I don't think we can really speak about African prostate cancer with one voice, really. What do we know about the diversity of the disease within the continent of Africa?

Kosj Yamoah: As we all know, there's a lot of genomic diversity on the African continent. And so when one attempts to study prostate cancer in Africa, one must pay attention to that as well. So for instance, there are different prevalence when you look at prostate cancer from East and West Africa, South, North. And so that means that we would need to even on in studying prostate cancer and a global landscape, pay attention to the subpopulations within Africa. So that also allows us to really study an area of prostate cancer disparities that is very nascent, but really exciting, which is the tumor micro environment. And then couple that with genomic ancestry, right? Because a lot of the populations of African American population come from the West African region. And there's some similarities to the disease presentation when you look at it that way. And hence we can now overlay, and I want to emphasize that overlay genomic ancestry to understanding the disease process pulled with the tumor micro environment, which will give us information about certain exposures that might pertain to subtype of prostate cancer in different populations.

And so the working in prostate cancer globally is just now starting. But has tremendous potential to really unlock a lot of areas of prostate cancer that is really exciting to be part of this. It's really important to recognize that our emphasis on disparities has been too focused on gene expression. And although that's very important, it's critical to recognize that a lot of information is missed when we don't look at the tumor micro environment and recognize how the processes that cause disparities could be mediated through differences in nutritional status, differences in exposures that would impact the microenvironment, whether immunostimulatory or immunosuppressive, that will ultimately impact disease process as well. And so in studying disparities in different parts of the world, we know that dietary patterns are different and these impacts the environment of either the tumor or even normal cellular processes. Also, there are genomic differences or gene expression differences based on tumor subtypes. Now the linkage is an area of intense investigation, but those linkages are important in order to understand where the intersection is and how we can better understand the disease process.

Charles Ryan: The PCF currently funds research in 28 countries worldwide. In 2021, we were proud to add five sub-Saharan African countries to the list of this group. These countries are focusing on patterns of care delivery, patterns of disparities and biological effects of prostate cancer in these unique populations.

It's very exciting to have you. Thank you so much for your time.

Kosj Yamoah: Thank you.