Alicia Morgans: Hi, I'm so excited to be here to speak with two authors on the Lancet Prostate Cancer Commission work that is out now in the Lancet. So excited to speak with both of you.

Nicholas James: Hi, nice to be here as always.

James N'Dow: Yeah.

Alicia Morgans: Wonderful.

James N'Dow: Pleasure.

Alicia Morgans: Thank you both. Can you just introduce yourselves, please? And we'll start with Professor N'Dow, please.

James N'Dow: I'm James N'Dow, Professor of Urological Surgery in Aberdeen in Scotland. And I'm Adjunct Secretary General and the EU executive looking after the education portfolio. And I was honored to work alongside Nick James who chaired this whole endeavor.

Alicia Morgans: Wonderful. And the chair himself, Dr. James, Professor James.

Nicholas James: Yeah. Nick James, I'm Professor of Prostate and Bladder Cancer Research at the Institute of Cancer Research in London and the Royal Marsden Hospital. And in this context, I chaired the commission over the last three years.

Alicia Morgans: Wonderful. Nick, we'll start with you. Can you tell me a little bit about why the Lancet put together this group, why there was a need to have this document and how you put together what was actually quite a large international group to put together this document?

Nicholas James: Yes, thank you. They've previously done commissions on a number of topics, mostly quite general like global surgery, global radiotherapy, women's health, things like that. And they then decided that they would move into more specific topics. And in the context of cancer, prostate cancer is the first one that they chose, and I was honored to be asked to chair it. Now they were very clear that we had to take a global perspective and a sort of 10 to 15 year or so timeframe. And also very clear that we had to have global geographic and ethnic representation. We didn't want a commission full of elderly white men, which obviously you could put together, but we didn't. The Lancet was very clear about that. We put a lot of effort into identifying people who met those characteristics who were at the top of their field in terms of their expertise, geographically distributed across a range of specialisms, such as urology, oncology, public health, patient representatives and so on. Public health and health economics as well.

Alicia Morgans: Yeah. And it was actually quite a large group. And as you mentioned, you've been working on the document itself for about three years and it's really quite a scoping document. Can you share what were some of the main areas of focus within this commissioned manuscript?

Nicholas James: What we decided we needed to do, 'cause we had a lot of us, 40 or so. And what I did with the original commissioners that we identified is we realized that having identified a whole lot of busy people, it was going to get hard to get them to write stuff, but not hard to get them to talk about it. We seconded in a whole load of clinical research fellows linked to my Stampede Trial from across the UK. They themselves are quite diverse and geographically spread in terms of where they come from, although not in terms of where they currently live. And we split them up into four working groups. One was looking at global health trends chaired by Ian Tannock.

One was looking at the diagnostic pathway, which James chaired. And then we had two looking at treatment, one looking at early disease chaired by Felix Feng and one looking at advanced disease chaired by [inaudible 00:03:46]. We had a whole series of working group meetings and we used that to produce a first overview of what we saw as the most important topics in each of those areas. And that ended up with me with a document of about 100,000 words, which has been sequentially edited down and then put through two rounds of peer review. We ended up with still a substantial document around 25,000 words with, I think, some quite interesting recommendations that the commission came up with.

Alicia Morgans: I would completely agree. And James, I'd love to hear from you. You chaired one of the sections, I think the section on diagnosis and screening. And when I think about that section in particular, and I also think about global practices around PSA screening, about under-screened populations, maybe over-screened populations, the differences that exist and the disparities that exist. This is in itself quite a large topic and I'd love to hear from your perspective, what were some of the conclusions, the main thoughts that came out of your section with this large group of people that worked on this?

James N'Dow: Firstly, I would say it was a bit of a shock when Nick asked me to chair that group because talking about early diagnosis or screening in prostate cancer, as you know, is always a very difficult conversation to have historically. And we had, as Nick pointed out, quite a broad range of expertise, different disciplines, urology, oncology, different parts of the world. Everyone came with a particular vantage point on this issue. And I think the first thing that Nick encouraged us to do actually is to have that conversation and to listen, to listen to people's perspectives, to understand them. And I think the challenge we had actually was that we weren't only dealing with one particular group such as high-income countries or dealing with just low and middle-income countries alone. We were dealing with the whole spectrum and having recommendations that were reflective of these two arenas actually took some work to reach consensus.

But I think with Nick's actually amazing amount of effort he put into this and his way of chairing how we worked, respecting everybody's views, we were able to address the thorny issue of overdiagnosis, if we want to call it that, in high-income countries. But the more problematic aspects of overtreatment and how do we manage, in inverted commas, screening more like risk-adapted early detection is what we were actually talking about in the commission. To be able to identify those that were going to have lethal disease and would suffer or die from their disease, how do we identify them to offer them treatment early? And not to pick up those that will not suffer or at least to identify those that are perhaps intermediate risk, that could still be managed by active surveillance to reduce the harms of treatment. That in itself was a conversation that we were used to having in high-income countries, Nick and I anyway, but I think when it came to low and middle-income countries, we're dealing with a different challenge, you see. We're dealing with a challenge where actually the issue is people are presenting with very late diagnosis, advanced disease, metastatic disease and dying and suffering and some of them not being picked up at all. And so the recommendations we ended up with, I believe, were actually very balanced insofar as discouraging picking up or at least treating diseases that will never harm a patient, whilst in low-income countries actually promoting the fact that, you know what, actually screening in that setting has never been tested. And actually, if there's an area where we are going to make a real difference in the lives of people, then it is in low and middle-income countries to test screening options to be able to actually reduce the harms and to deal with the surge to come. It was fascinating but challenging.

Alicia Morgans: And just to follow up on that, I think one of the other points was that there will be a surge to come of patients, people with prostate cancer who are diagnosed. And I would appreciate if you could comment on that too. And how did you come to that conclusion and just explain to the listeners what you expect.

James N'Dow: Well, I mean we were blessed to have representation from really strong organizations like IAC that have done a lot of work in terms of trying to map the trends in prostate cancer over the years and to be able to come up with projections. And it was clear that from all the amazing work that has been done by organizations like IAC and also from personal experiences of people practicing in low and middle-income countries that were part of the commission, it is clear that actually we will have a surge. It is actually underway and there are so many people actually not being diagnosed. And so it was clear from the data that was available to us that if that trajectory is followed, then the surge is coming and it will be a big surge. And what is even more troubling is that actually we are not prepared, right?

We're not prepared for the surge. If you look at low and middle-income countries, take parts of sub-Saharan Africa as an example, we are nowhere prepared for effective evidence-based early detection programs, right? We want to raise awareness, we want to ensure that health professionals and patients and the public are aware of the need for early diagnosis or earlier diagnosis. But we're not prepared. At the moment, we clearly have a very big issue with managing advanced disease. We are not doing very well with that either in terms of palliation and other treatments. We have a big issue now with advanced disease, but if we are going to raise awareness and do early detection in low and middle-income countries, we are not prepared for the management of earlier disease in terms of that stage shift that we will pick up. And this was, for me, one of the exciting aspects of the work that Nick and the commission have led. How do we prepare for that surge that is going to shift to requiring more radiotherapy for localized disease or more surgery for localized disease.

That capacity building and investment in infrastructure at the moment is not there, and we need to get funders, politicians, and all of the stakeholders to recognize that and deal with it.

Alicia Morgans: Absolutely. And along those lines, from a global health perspective, one of the other key aspects of this commission manuscript. Nick, would you mind just commenting on what kind of recommendations and guidance were incorporated from a global health perspective to deal with that surge, to address the issues of diagnosis, and also to address some of the disparities that we know exist, certainly between higher income countries and lower and middle-income countries. But even within those groups, there are certain groups of individuals who are at even higher risk with more aggressive disease and higher rates of mortality.

Nicholas James: Yeah. We're projecting that in sub-Saharan Africa, for example, cases of prostate cancer are going to double in the next 10 to 15 years. And against the background of treatment not being that great at the moment, just saying we have to adopt the model that we're using in London or in Chicago, Boston, whatever, simply doesn't work. We need to set up diagnosis systems that we can scale now. Nurse-led systems linked to education, and one of the things that we're recommending is that it's not just prostate cancer that's going to go up, it's other diseases of aging.

And so in the project we've just been doing called the man van, we've been testing for hypertension and diabetes, and fully 50% of the men that came through the van had one or the other of those conditions as well. These are all things that are going to kill you prematurely if you don't do something about them. And for all three of those conditions, you're much better off picking it up and treating it early than waiting for a catastrophe to happen. And it doesn't really matter who's paying for your healthcare, if you're paying for it yourself or if the state is paying for it, you'll pay less if you pick things up early. We make recommendations around cost-effective ways of doing this, and they apply in the high-income setting and in the low-middle-income setting. And I think one of the things that's very striking in the UK, for example, but it again applies in the US, applies elsewhere, is that deprivation and being from an ethnic minority are really bad things for you in terms of getting less good healthcare outcomes.

And James may well want to comment on this as well, but I think there's a lot of victim blaming attached to, they don't turn up for testing, they don't whatever. And actually, it's our fault as doctors and health professionals that we're not organizing things so that people can turn up or know that they need to turn up. We stack the dice against you. Even in the UK where healthcare is free, your access to a GP is governed by how easy it is to get time off work. If you have an appointment system that means you have to phone up at 8:00 in the morning and come when the NHS says it's convenient for the NHS, you're stacking the odds against people who are from less well-off backgrounds. You need to adapt the systems, and this applies even more so in poorer areas of the world.

Alicia Morgans: Yeah. James, do you have thoughts or comments on that and how we can address that?

James N'Dow: Yeah, Nick is right. Low-income countries would be one area where we can talk about. But even if you look at the UK, as Nick is referencing, there is quite a bit of variation across the UK, right? If you look at some of the publications recently where they're suggesting if you're in London, in some pretty well-off area in London, the risk of you showing up with metastatic disease is perhaps, I don't know, 8%, right? But if you live up north, be it north of England or even in Scotland way up north, that can go up to between 20 to 30%. I think clearly awareness raising and access to the care that you need are things that are not only challenging in low and middle-income countries, so we shouldn't forget about that. We need more evidence-based implementation of what we know works even in high-income countries to mitigate that imbalance that exists. But it is exacerbated multiple fold in low and middle-income countries where awareness in outreach areas is extremely poor. But also access is almost impossible for some of them for many reasons, including financial, right? And these are issues where while PSA testing in Aberdeen or London or Paris is a controversial topic, certainly in low and middle-income countries, it is perhaps far less controversial because it's a gateway to us being able to pick up diseases that would otherwise come in very advanced stages leading to harms and death.

Nicholas James: Yeah. And I think one of the things that's followed on from this is that I've had a series of conversations with public health people in Lagos, and they are very, very well aware of the issues that we're raising but haven't really been doing very much about them. We're discussing with them setting up a sort of outreach testing program. And one of the things that's really interesting about discussions we've had is that there are currently very few publicly funded or publicly accessible, as opposed to privately accessible, linear accelerators outside of South Africa, Egypt, and one or two other places in Africa. But they're busy building them very rapidly in Nigeria, and also they're setting up comprehensive health insurance schemes, which they struggle to get people to sign up for. One of the things that we've been discussing with the group in Nigeria is part of the enticement to come in and be tested is that you get registered for a health insurance scheme at the same time, which they have to pay into, but it's a relatively modest sum of money even by local standards, and it gives you access to treatment. And then there's been a further very welcomed paradigm shift in radiotherapy, which is, if you were talking to me about having radiotherapy 20 years ago, I'd be talking to you about you coming for two months for treatment.

Whereas we now know you can deliver radical radiotherapy in five fractions, you can probably deliver it in two. That makes regional centers much, much more viable if you only have to travel and stay there for a few days and you go home treated. The same applies to surgery, of course, with minimal access surgery; then you don't have to have a surgeon in every town or a radiotherapy machine in every town. Like Uganda, for example, has set up four regional radiotherapy and surgical treatment centers with the plan that you refer people in. There are different ways of doing things now that are scalable in settings where currently care is not necessarily often very good.

Alicia Morgans: Well, I think that the place to start is bringing together a group like you did and really scoping out the problems, talking about where we want to be in 10, 15 years and really laying the groundwork, at least in a hopeful way, of how we can get to that place and how we can raise the level of care across all of these domains that you've assessed for patients around the world. I so thank the two of you and wonder if you have just one last comment, one final message if you had to give it to readers. Clearly, there's more in this document than we can cover in a ten-minute conversation. But James, what would your message be to listeners?

James N'Dow: I would say our responsibility, recognizing that even though we had decent data to work on for the commission, is that we must do better to get better quality data at a global level. And in this day and age, with huge platforms collecting real-world data across Europe, funded by the European Commission, platforms like that could easily be extended to low and middle-income countries for people to collect data reasonably accurately. The fact is we have technology such as AI and other things that could help low and middle-income countries that have, say, issues of lack of pathologists, for example, to ensure that the majority have access that allows them to have basic decent care. I think this is our responsibility and one that I was really proud to be a part of this commission and to work under Nick's chairmanship because he came in with absolutely the right attitude. And I'm hopeful that these recommendations will be implemented. I'm hopeful.

Alicia Morgans: Wonderful. And Nick, as the chair?

Nicholas James: Yes, thank you for those kind words as well. I think one of the things that we've mentioned in the report is the need for education, outreach, and connecting people. And I think one of the key developments of the last 20 years has been the smartphone. And so in most countries in Africa, the level of use of smartphones sits at about 90%. You've got a ready-made tool for disseminating information, managing people's patient records, and also empowering them because if your record's on the thing, then plugging in things like AI can make recommendations that are personal to you for treatment. The health professional you're seeing doesn't need to be an expert on prostate cancer. They just need to know who you need to be treated by. And often the treatments are quite simple, hormone therapy and so on. I think the smartphone is potentially transformational here in sticking all of these different aspects together that we've been discussing.

Alicia Morgans: Wonderful messages. We've got to count people, we've got to get their data in order to better help serve them, and then we have to harness the technology that's already existing around the world and amplify ourselves, amplify our messages to get people the information and the care that they need. Wonderful, wonderful work. Congratulations again to both of you. We will have to talk again because there's too much in this particular document to cover in one recording alone. And I just so appreciate your time and your expertise today.

James N'Dow: It's been a pleasure.

Nicholas James: Thank you.