Charles Ryan: Hello from Basel and APCCC 2019. I'm delighted to be joined by two guests to talk about prostate cancer as a problem in Africa. I'm joined by Kosj Yamoah who's an Assistant Professor in Radiation Oncology at the Moffitt Cancer Center in Tampa, Florida and Professor Ngozi Ekeke at the University of Port Harcourt in Nigeria. Both of you delighted to have you here speaking with us today about the problem of prostate cancer in Africa. So let me just start out by saying how different is the problem of prostate cancer in Africa than it is in the United States?

Kosj Yamoah: I'll tell you it's very different on multiple levels. First, we have two major aspects of prostate cancer in Africa. As much as there is a common theme that there is a growing incidence and mortality among the African diaspora, either living in the United States or even in the Caribbean Islands or the United Kingdom and back home in Africa. There's also the question of not only the increase incidents but the later stages of presentation, as well. And so there's a duo problem where we don't fully appreciate if that biology is just aggressive in nature or is it late diagnosis that compounds the problem. But across the board that means that prostate cancer at least in the West African region and my colleague Ekeke will attest to that, is actually has been known to have been in the cancer registry is become the second leading cause of cancer mortality among men in the West African region.

Charles Ryan: Okay. And how are men in Africa presenting with their diagnosis of prostate cancer typically?

Ngozi Ekeke: Yes, they present late. First of all, there's a lot of ignorance and superstition about the cause of disease. However, with the introduction of screening and PSA and all that, there is a changing pattern. The presentation. We are seeing a few cases that are presented early that can be offered radical treatments and then we still have the majority of them presenting late. But some of the challenges we have just as in this APCCC conference, we discover that the studies that are done, but the genomic studies. They're not doing in Africa. We are limited. We are talking about PET scan here. We hardly had them in South Africa and the populations that are used in randomized clinical trials for all these drugs, they don't consider Africa. So we are trying to advocate that for you to know the pharmaco-ethnicity problems that are rising for us to get a really global picture.

Charles Ryan: Right.

Ngozi Ekeke: It would be nice to look at Africa. For instance, in West Africa over 25% of the population of Africa live in West Africa and if they are not considered in such studies. So that's one of the challenges we have in Africa. Also, we are generally low-income countries and so some of these drugs that are being provided, we hardly use them. For instance, we just have abiraterone coming into our market, but at a very expensive cost. We can hardly have enzalutamide. Yes, so that's some of the problems. Then the health, we don't have a very good health insurance scheme. So it is individual. They pay out of pocket and because of that, it is very difficult to sustain the payment for both the investigations, as well as the treatments that are offered.

Charles Ryan: Are patients paying out of pocket also for laboratory tests, as well as drugs?

Ngozi Ekeke: Yes, so because of that, the outcomes are also affected. So the Brazilian consensus, which we just had in this will also help us because they are talking about those adjustments of abiraterone for instance and the use of other facilities.

Kosj Yamoah: Yeah, there's a very interesting initiative with the NCCN. There's NCCN Harmonization that is looking at harmonizing the African countries in terms of the guidelines that are put forward and what Prof Ngozi Ekeke is talking about is very important because what the NCCN is doing is they're going to have a document that outlines specific metrics that are supposed to be adhered to by across the African continent and then color code the different ones based on price and to allow some sort of consensus across the board saying that these are recommendations that should be adhered to but based on availability like you said, abiraterone, any new agents, these are also approved by the FDA, but it's going to be stratified based on price. And I think that's going to be a good metric to allow all the centers to optimize their treatments but still have the knowledge of what's available even though they may not actually be doing it yet.

Charles Ryan: Right. And I also wonder, the Brazilian consensus conversation yesterday, there were some really interesting points brought up about docetaxel, abiraterone and the ways that we can give these therapies in a more cost-effective manner. Abiraterone is a drug that I've spent studying my whole career and we know that when you give it with food at one quarter of the standard dose, the pharmacokinetics are very favorable, especially if it's a fatty food. And that can right there reduce the cost by a quarter. I think there's actually more mileage we can make by looking at post pharmacogenomic properties that can identify a patient population who can actually potentially get by with even lower dose than that. So there's a lot of research on this feasibility and cost-effectiveness that are biologically driven.

Kosj Yamoah: Absolutely. And talking about that, we're looking at genomics and lack of inclusion of these patient samples from the African continent studies. We know that we are getting all these clinical trial approvals based on large randomized studies. We also do a lot of personalized medicine in this space from the data we have from tumor genomics and I believe that if we don't really harness the rich genomic data we have from prostate cancer to most African continent would actually worsen the disparity with the advent of personalized medicine.

And so we're looking at a simple genomic test like the TMPRSS2: ERG fusion was initially identified in about 60% of prostate cancer samples, mostly European origin and was incorporated into diagnostics. It turns out that African American patients only have that fusion in only 25% of the time. When you go into the African database, we did a study in Ghana, it's actually on the order of 10% to 50% TMPRSS2: ERG fusion, positive tumors. So you have 90% of African cases that are prostate cancer that do not have the fusion. So as a diagnostic tool, you're missing 90% of African cases. Right? So there's a lot to learn and actually harness that in the genomics, as well.

Charles Ryan: Well, you're a radiation oncologist. What about radiation therapy in Africa? I know that's a very broad question, but-

Kosj Yamoah: You know there is Cobalt had been mainstay of treatment and I have to say that Cobalt is actually evolving. The use of Cobalt therapies are evolving because now we do have 3D conformal technology with cobalt, as well with mortality of applications. And there is value to that because there you have stable electricity to be relying on all the time, right? So the developing cobalt technology and putting the advanced technology on that Cobalt system to make it effective at delivering image guide achievement is the way of the future for [crosstalk].

Charles Ryan: We don't follow this as closely, including myself. Why is Cobalt a preferable isotope?

Kosj Yamoah: So Cobalt is a natural source, right? So once it's there, you have it. You also have, it has a relatively longer half-life, right? So you have this natural source of gamma production. And what happens is that as long as you can have it shielded, all you need to do is to open up the exact aperture for the radiation to be exposed onto where it needs to be. And so there is more is most stability in terms of ability to generate the energy you need to treat the cancer. The problem is that it's also, you cannot modulate that energy. It's fixed. So an average of 1.25 megavolts and that's what you get, right? And so what ends up happening is that when you're doing ... You maybe have a bigger body habitus or so other patients that you need a little bit more energy. You cannot really rely on the Cobalt, so you get more skin toxicity and other things. So all Cobalt machines we just box up with maybe some blocks to block the radiation fields. Now we have these leaves that can actually shift the beams to allow you to be a little more conformal. And also with the advent of onboard imaging with the Cobalt, you can actually image exactly where the tumor tissue is and treat and these are advancements that are coming on top of that. And maybe with cost reduction of these advancements, you can actually get into the market and allow the African continent to really treat patients appropriately.

Charles Ryan: Now in the United States, it's a huge problem if you're going to get radiation every day for eight weeks. Getting to the center for radiation and if a patient lives 25 miles away, it's extremely difficult for them even with a functioning highway. I would imagine that in Africa there are geographic challenges where the patient lives and where the center is, correct?

Kosj Yamoah: Well, there's hope for prostate cancer. I have to say it because looking at where the field is going, let's look at localized prostate cancer for a second. We have moved from nine weeks treatments. So now given SBRT treatments for five days or we had the fractionation for four weeks. We've also, with the advent of oligometastatic disease with SBRT, we can treat spot lesions. All of these technologies plus HDR brachytherapy, which is a one day, half a day procedure. We can harness these shorter courses for treatments in limited-resource settings that can actually expand the ability to really cure the disease without having to deal with all that you talked about. So even though it's a convenience in the United States, it's actually an economic benefit when you use [inaudible] in a cost-effective in Africa. So absolutely. I think this is all the things I'm very excited about.

Charles Ryan: It's interesting overcoming that barrier.

Kosj Yamoah: Absolutely.

Charles Ryan: Professor Ekeke, in Nigeria, a massive country, what do you view as the most significant challenge for a man diagnosed with prostate cancer now? Is it the availability of therapies? Is it geography or-

Ngozi Ekeke: Well, one of the problems is cost because it's a low-income country. So the very few of our people can provide the necessary financing so they can even be treated outside Nigeria. But a lot of the population, they don't have the money and because of lack of the national health insurance support. So that is one problem. And then like we learned yesterday about the Asian population having a pharmaco-ethnicity. Now there is relative neutropenia in Africans, relative neutropenia, and other hematological indices. Generally, there is relatively low levels of hemoglobin and so all these drugs that we are using, we have not even done any study. In fact, as one of the things that I've told my colleagues after this meeting, we're going to do a study that is similar to what the Asians have done to see whether there is any difference in side effects following all of these therapies that we have.

Charles Ryan: For docetaxel specifically.

Ngozi Ekeke: Yeah, specifically.

Charles Ryan: Now, is docetaxel readily available?

Ngozi Ekeke: It's available.

Charles Ryan: Yeah.

Ngozi Ekeke: Yes. But we still have some other problems. Genetics. So we have problem of regulation of the drugs that are coming. And so you may not even get the real docetaxel, another small dose. So those are some of the challenges. And then, we also will do better if we have some more support in terms of training. Presently we're doing operatical prostatectomies for early stages. We just have two new [inaudible] machines that have been installed and also the vast population of about 200 million. And you just have two such machines. Brachytherapy is not really available. What we do is to send to some other countries, South Africa, Ghana and outside. So we are limited in terms of availability of both the equipment and then skills and some other. Then the other thing is ... So we are still doing orchiectomy. We're still doing orchidectomy. If you check androgen deprivation, the majority of patients still get orchiectomy.

Charles Ryan: There's many in the US who think we should be doing our orchiectomy here more frequently because it's ... Why do we need to give injections that cost several hundreds of thousands of dollars every few months when we're going to maintain castration throughout the life of the patient? So that's an ongoing discussion in many parts of the world.

Kosj Yamoah: That's so true.

Charles Ryan: Yeah. Yeah.

Ngozi Ekeke: So the other thing, like I mentioned earlier, research. For instance, if we can get our patients into all these genomic studies, it will help us to also know whether there are some peculiarities. So those are some of the challenges we have.

Charles Ryan: Well, it's really great to talk to you and great to have you here as part of the international dialogue. I hope next time we convene in the APCCC, which I suppose is in 2021. We have a much greater African contingent and we hear more about not only the challenges but also that progress is being made there, enrollment in clinical trials, the development of infrastructure, databases and it certainly sounds like the pharmacogenomics is an area where we need to make some progress.

Kosj Yamoah: And one last comment I want to make. My conversations with Gina, we talked about APCCC's involvement in AORTIC and AORTIC is basically ... They are a bi-annual conference for African oncologist. They meet every two years to really talk through the global problem in Africa. So I think that's a dialogue that is ongoing. It'd be nice to see that developing Africa.

Charles Ryan: Absolutely.

Kosj Yamoah: Thank you.

Charles Ryan: Great. And my university and many universities in the United States have partner institutions in Africa and other parts of the world. And so there's a lot of potential there, which is really great.

Kosj Yamoah: We can just work together, make it happen.

Charles Ryan: I hope so. That's great. Well, thank you both.

Ngozi Ekeke: I've also spoken to Morgans and [inaudible] about the IRONMAN Project.

Charles Ryan: Yes.

Ngozi Ekeke: So that Nigeria and other African countries can be listed.

Charles Ryan: That would allow ... I mean, IRONMAN is a great example of being able to tap into that global stream of knowledge collecting genomic and outcomes data. And I certainly know that there's an interest in expanding that effort throughout other parts of the African sub-continent where it has already started. Okay.

Kosj Yamoah: Thank you.

Charles Ryan: A pleasure.

Ngozi Ekeke: Thank you.