Charles Ryan: Hello from the APCCC 2019. I'm delighted to be joined by my friend and colleague, Dr. Christopher Logothetis. Dr. Logothetis is the Department Chair and Professor in the Department of Genito-Urinary Medical Oncology at the MD Anderson Cancer Center in Houston. Chris, I want to talk to you about a couple things. You're here at the APCCC, your topic that you're going to be talking about is ethnicity and outcome in prostate cancer. This is a very global conference. Prostate cancer's a global disease. And I think it's imperative that we understand the differences in outcomes of individuals based on race and ethnicity. So tell us what you're going to talk about.

Christopher Logothetis: Yeah. So this is not a topic of frankly primary interest in my long time. And so it gave me a very fresh view. So to prepare for this, I had a chance to look at it clearly with a relatively unbiased approach. And I'm struck by the assumptions that many of us carried was that there are very differences in ethnicity, expose patients to great risk for under-treatment, mistreatment or over-treatment. Because we make assumptions, for example, that I often hear Asian descent individuals are at lower risk, African-Americans are at higher risk and the like. And when you look at the literature in great detail, you realize how superficial and how lazy these conclusions have been. So when I look at the data I look at, yes, there appears to be a racial distribution and a geographic distribution differences in outcomes. And there appears to be differences even in the prevalence of some genetic abnormalities. But when you try to dig just a little deeper, is that difference because of differences in pattern of practice, in detection rate, how deployed diacaustic are meaningful, it starts falling through.

Charles Ryan: Yeah.

Christopher Logothetis: So there are some data apparently that Ros Eeles actually presented here briefly to suggest that there may be some meaningful genetic differences within group. But my fundamental conclusion is there's smoke, but there's no fire.

Charles Ryan: Interesting.

Christopher Logothetis: And the second thing is that you're probably going to harm patients if you replace racial background or geographic background with decision making that should be based on clinical staging and genetics. That should trump it. A low stage, low-grade African-American should not be told based on present data that he's at greater risk than his equivalent Caucasian patient.

Charles Ryan: And that's an important message.

Christopher Logothetis: I think that that's very, very clear, because the biases of over-screening and under-screening groups based on that, we know exposes them to risk. So I think that the data is clear for governments.

Charles Ryan: Right.

Christopher Logothetis: And for national initiatives. We've learned in the United States how costly the unregulated disuse of PSA has been. The same thing may happen with genetics and the same thing we discussed with the use of the PSMA PET. So I would argue that this is a good time for them to learn from our mistakes, and design the proper studies to understand what it is that appears to account for some of the reported differences. Is it biology?

Charles Ryan: Yeah.

Christopher Logothetis: Pattern of practice?

Charles Ryan: Yeah.

Christopher Logothetis: Deploying technologies? And I think that that's key.

Charles Ryan: It's an important, sobering message, and a realistic message. And I think it's actually in a way realistic, or reassuring to hear that biology of disease is what our target should be. It's probably still the most-

Christopher Logothetis: Correct.

Charles Ryan: ... important thing. That said, I in my own research had been very intrigued by the fact that prostate cancer is, I think unique among cancers in its host versus disease relationship. Because there are genetic variances in, for example, androgen metabolism that are incredibly vast ranging from polymorphisms in androgen supply genes and that kind of thing that we're studying that are really quite fascinating. And those are drivers of the disease, but they're host factors.

Christopher Logothetis: Yeah.

Charles Ryan: And so you know-

Christopher Logothetis: So we share that view. And the complexity arises is that those alterations may predict for vulnerabilities to androgen ablation or are our primary therapy.

Charles Ryan: Right.

Christopher Logothetis: So if you measured at the level of antitumor activity, you may get one result. If you measured at the benefit of the patient, you may get a different result. Because they may also be predictors of morbidity from therapy.

Charles Ryan: Yeah.

Christopher Logothetis: So this unique feature of prostate cancer, which I wholeheartedly endorse with you, is a two dimensional game of hosting epithelium. And by the way, our animal models have very different steroid-

Charles Ryan: Correct.

Christopher Logothetis: ... metabolism. And the superficial associations that people make are one of the biggest drivers are very different in most of our [crosstalk 00:04:49].

Charles Ryan: But in your view, is a third dimension going to be geography? I'm amazed now what we're seeing for example, when we look at microbiome data. And that's probably a surrogate for geography, or it's a surrogate for diet obviously. But diets differ around the world. And I think the complexity gets very high, very fast when we start to see data like that.

Christopher Logothetis: Correct. So this notion of what the exo-environment is and how it influences us is obviously a big field.

Charles Ryan: Yeah.

Christopher Logothetis: There's very little data on prostate cancer obviously. But the notion that this won't have an impact is probably small.

Charles Ryan: Right.

Christopher Logothetis: When we look at our image studies, our scans, and we can measure truncal adiposity and by and the like. You see varies differences in prognosis. Now that is, is it biology of the host that somehow relates to the biology of the tumor, or is it all external? We don't know.

Charles Ryan: Right. That's a very complicated topic. Yeah.

Christopher Logothetis: So it needs to be studied, siloed with an eye toward integrating the data-

Charles Ryan: Correct.

Christopher Logothetis: ... at some level.

Charles Ryan: That's a good way to put it. Yeah. So we need to support the microbiome work. We to support the metabolism work. We need to support the tumor microenvironment work, immuno-oncology work. But there is probably a-

Christopher Logothetis: There's a unifying concept there.

Charles Ryan: Unifying concept there.

Christopher Logothetis: So the definitions in the framework need to be retained in order to ... So have an eye toward integrating that data when it matures.

Charles Ryan: Well, I can think of no better messenger for the need for a unifying concept around that topic. And I'm so glad to be ... I'll be looking forward to your talk.

Christopher Logothetis: Thank you. Thank you.

Charles Ryan: And so glad to be able to talk to you today.

Christopher Logothetis: Great.

Charles Ryan: Thank you for joining us.

Christopher Logothetis: Thank you.