Charles Ryan: Hello. Today I'm joined by three guests working in Tanzania at the Kilimanjaro Christian Medical Center and the Kilimanjaro Clinical Research Institute who are the recipients of a Pfizer Global Health Equity Challenge Award from the Prostate Cancer Foundation. I'm very happy to introduce our three guests today.

The first is Prof. Blandina Mmbaga, who is a professor of pediatrics at the center as well as Dr. Alex Mremi a pathologist and Dr. Nicholaus Ngowi a urologist and they lead the team that is taking on Awareness, Barriers and Clinical Factors Surrounding PSA Screening Among Men in Northern Tanzania.

Congratulations to all of you for receiving this award. And thank you so much for joining us. We at the Prostate Cancer Foundation are extremely proud of these awards and very excited to hear about the work you're doing. And what I think I will do now is turn it over to you Prof. Mmbaga for a brief presentation and then we'll have a conversation after that.

Blandina Mmbaga: Yes. Thank you very much, Dr. Ryan, for inviting us to the UroToday session today. Together with my fellow Dr. Nicholaus Ngowi a urologist and Dr. Alex Mremi a pathologist, we are both at the Kilimanjaro Christian Medical Center. And I'm also the director of Kilimanjaro Clinical Research Institute.

Based on what we have been seeing in relation to prostate cancer, especially people presenting late at the clinic, it did drive us to think of looking into awareness and if there's any barriers to screening and also correlate the prostate cancer with PSA among many in Northern Tanzania.

And in thinking about this, when we saw the Pfizer global grant, it was of interest for us to think about screening for PSA in Tanzania because it's not a normal activities which is happening first of all. And the second, if people want to access PSA it's quite expensive and they would access it to a private facilities.

For this case, many men are not screened. And the issue of digital rectal examination is quite a challenge, it's not friendly to most of the men. And with taboo and cultural in this area it becomes like something people don't want to do it unless they're sick and they're forced with the condition.

So blood screening, we thought it would be a very good thing to start with and see the readiness of the men into screening and what they know about prostate cancer. So as we know that prostate cancer actually is a challenge and a problem all over the world and prostate cancer is common also at KCMC.

From our cancer register at KCMC which is way back, 2000 to date. We tried to look from 2015 because our cancer care started only 2016, to see the cases of prostate cancer. And we thought that there are around 1,487 recorded cases of prostate cancer.

And in looking at our four main regions which are making the Northern zone, we could see that Kilimanjaro region, where the Kilimanjaro Christian Medical Center is as a referral hospital, patients were 78% of the total number. While the region from Arusha around 12%. Tanga 5.9 and Manyara, 3.1.

We thought that maybe the Kilimanjaro, the number is higher because it's the hospital catchment area and nearby people. And some of the patients might come to their relatives and they could still mention that they're coming from Kilimanjaro, but we really wanted to know what is going on and what the real situation within this area.

So with the Pfizer grant, we then thought of doing it in three regions in Tanzania based on the budget. And we see actually what is going on. And we thought of reaching into the community and do a community-based survey in Northern Tanzania, where we initially thought of only the three regions and the three districts in each region.

And for that case, we estimated around 1,200 for the three region, that's 3,600. But it happened that we had also a CIRGO funding, which one of our colleagues, that's why we united not to do different. Dr. Alex Mremi got a grant for three districts in Kilimanjaro. And we thought why don't we work together because we had the three districts Kilimanjaro. Yeah.

So that we covered the entire Kilimanjaro region and where we know that many cases they are coming. And that's why we see as together and with a very higher sample size. So from this a grant, it was 150,000 USD from Pfizer. And we worked on the ethical approval, which we obtained the initial ethical approval, local one in December.

And we got the national approval in March and all the process of approval, this including getting the government letter and permissions to go through this all regions for the screening of prostate cancer. That's why we say we got all the permission in May.

And this one I have already explained about the initial regions, which we were to do only three, but now we we'll do actually at least four regions just to cover the entire Northern zone of Tanzania, but Kilimanjaro region, the entire region which has seven districts.

This was of very big interest from the regional administrative office as well as the regional medical officer. They wanted really us to cover the catchment area of Kilimanjaro so that you can come with the data which might be representative of the Northern zone and can help them to do and understand the challenge and the problem.

So we did launch our project in May, 2022 with our regional medical officer here, Dr. Gile, who came to launch on the official day and the event and myself I'm here. But also the same day we started screening it was flooded because we had more than 100 men and we never expected.

That time we prepared two nurses and two data entry, but coming to the launch period at 1:00 we had to shout at the hospital and they sent us three more nurses and some data entry team, because we could not withhold the volume of people who were coming. And the first day actually could not do all the people.

We had to write other people, like giving them appointments for coming. How and why this happened? Because of the awareness and the actual advertisement we did in the church, the mosque as well the municipal car supported us to go through the municipal for three days announcing to men.

And while continuing I could say the feeling which I had on that day from men, one of the thing was like, "Thank you, ma'am, because men were forgotten. You always thought of women, but now at least someone is looking at us." And the other comment was, "This is very good because it used blood and not another way of looking for prostate cancer."

Yeah. So those were the kind of the initial. So we thought of screening once, one week, actually in each district, but this first district it was impossible. Because the first site which we did, at the end of the first week, we had a big number of screening, but still we left a lot of people.

We have to discuss, and the management request us to continue the next week. So in the first Majengo site, we had to do it two weeks, but we had to open another site in the urban Moshi, the Pasua. So that the Moshi municipal, were to do three sites in two weeks because of the need and how people wanted the service.

At the end, we said, no, because you cannot keep screening regular because still people are calling and they want the service. And we put maximum of two weeks in a district based on the need and five days. And after the screening, especially after the first two weeks of screening in each region, we are planning for a week of trucut, yeah, biopsy.

For all people who are found to have PSA of above four, we are inviting them back to get a trucut biopsy and further cancer screening. But for those who are heading below four, who are sending them a text message to inform them that they don't have so far the alarm, but we need them maybe in the next six months, if still we'll be running, or one year for repeating testing.

And the most important thing I would say is also how people were anxious to know the results, because they're calling us a lot if they see that there is any delay and they memorize their participants numbers because whenever they call me, I ask the number and then we send the results. That is quite very important.

And so for PSA we give the results between three to seven days, but we found that the realistic is seven days, because after the field work and all the sample coming and being done, then at least the next week when we are going a second week we can be able to start giving the results of the previous week.

And so giving the trucut biopsy results, it has been also a work which needed time because it'll need counseling, especially for those with the prostate cancer. Dr. Nick has spent in this time. And over the weekend I learned that he's going to these health facilities to sit with participants so that he can give extensive counseling and refer them for treatment at KCMC. We shall take the challenge.

And you also did the focus group discussion for each region, at least so that to learn more from the group discussion on the awareness and barriers. So this is our screening schedule which we are following. We're strictly following this schedule. And all the dates are like the way we are doing now. Today we are in Tanga region. Yeah.

So people are screening currently this area, they're in Korogwe and Bombo Referral Hospital. So we are having two groups now. And each group is having nine people, including the driver, the data entry, the ultrasound person and the doctor. And so nine people are going for each site.

And next week they'll be in Handeni, so that we can finish the Tanga region. The other week then from 19th of September, they'll be taking trucut biopsy in Tanga region. So after this is when we can see the resources, if possible then can we go to Manyara.

So preliminary research as of today, as you can see, actually majority of people in the age of 51 to 70, who this is about 62% of this group. You can see the mean age is around the 60s. Though we are calling men from 40 years of age. And you can see so far we had actually, the site which we have completed is Kilimanjaro.

And Arusha we completed, we are waiting for trucut biopsy. You will see I updated the results. We have got PSA results for Arusha, which I have added already. So when we look at Kilimanjaro, we had around 3,200 people who attended for screening for the entire seven district of the Kilimanjaro region.

And Arusha is around 1,158. This is making a total of 4,391. And we looked at people who are having health insurances only nearly 40%. And this is coming with a huge challenge for people with prostate cancer, because when you call them and when you cancel them, most of them cannot start the clinic because it needs initial investigation.

Even if they're going to get maybe free treatment support, but they have to go through some investigation, some consultation through the hospital channel. And this is becoming a challenge for them. A history of hypertension and diabetes, as you can see, this is part of the population.

Initially, we need not to plan actually to do blood pressure or screening the first day. We were then requested by the regional medical officer and the team that it's quite important we look at other comorbidity which might be linked to it. As a result, we amended our work and started doing this request from the authority.

And as you can see from Kilimanjaro and Arusha alone, awareness or good knowledge of prostate cancer is only 19%. Yeah. So that means this is one of the challenge. And look at the seven district of Kilimanjaro region, around 476 people had higher PSA of more than four.

And 305 underwent the trucut biopsy while 105 over the 305, which is 34.4% had biopsy confirmed prostate cancer. And so overall I can say instance of prostate cancer in is 3.2, but incidence for those who went to trucut biopsy 34.4.

This is what make us thinking that those who we found that maybe they're negative currently, or those who have not yet agreed to come for trucut we still need maybe to follow them slowly and make a cohort maybe of long-term follow up if we can.

So that we can be able to repeat doing the PSA and see the correlation of the higher PSA. If not now maybe even in the future, what might happen. And if you look at the Gleason score, you can see that the high score was around 12% and the intermediate 55%, while 32% are the low score.

So from this one, we could say that there is poor knowledge and high incidence of prostate cancer among at risk men in Northern Tanzania. This actually call for immediate intervention or community awareness and possible implementing the screening to the population because when they're very sick, it's very costful.

I could tell you only yesterday, our minister of health has announced it from the newsletter, how the National Health Insurance had been burdened by chronic diseases. And first off, the disease mentioned there was cancer, then renal disease, then hypertension, diabetes. And this is one something to think about rescuing the health system.

So if we look at this, this is the number I have already said, yeah, in the previous slides. In Arusha, we had 1,149 screened and we have elevated PSA 153 and nearly 10%. And we have 103 who have undergone trucut biopsy.

So I hope by the end of this week or next week Alex will be able to give us the biopsy results so that people can start counseling. But at least for Kilimanjaro we have 105 people who did never know that they have prostate cancer. Yeah.

Charles Ryan: I'm looking at those numbers on the bottom of 1,149, you have 153. So that's maybe 12% or so with elevated PSA and your you're biopsying most of those. We quote the number in the US, for example, that one in eight men will get prostate cancer in their lifetime.

One in six black men will get prostate cancer in their lifetime. And so what you're looking at is an incidence that is the number of elevated PSAs that is about that number, a substantially smaller number of those will actually have positive biopsies as you indicated before, but this is just through one year of screening.

So if we follow this group of patients or subjects men over the course of the next decade, there will probably be more positive cases. I'm just comparing this to what we're seeing globally.

Blandina Mmbaga: Yeah. Yeah. And that's what we think, if we can be able to follow up. Yeah. We have actually had a dissemination of our results because for the first time there was the first Tanzania International Oncology Conference which took place in Arusha 1st to 3rd of August. And we submitted our work for poster. We realized it late and that's why it went under poster.

There wasn't actually a lot of attention and especially it's not common for prostate cancer screening. So we'll work in future for the international conference. We are happy that the Prostate Cancer Foundation have invited us to present, but also we'll work on the manuscript submission.

So from here, because it was a highlight, what have we learned now from them from the field? First of all people are ready for screening. Yeah. Because you could see how people attend, but this is not easy, it's because we had sensitized. And now in each region, we have to do a massive sensitization because without that we see the challenges.

Yeah. And also screening is not available for free, the PSA screening, and health facilities do not have this service. And for that reason, it's available in private hospitals and it's expensive. So it's not a service which people undergo to do.

And for us, we see that there's higher prevalence of PSA in the community because it is not the way maybe we expected and think public engagement is quite very helpful to create awareness for people and building knowledge, and also supporting people to realize that they need to make checkup.

And low number of people with insurance is a problem as we see it was only 39%. And this create a challenge in accessing care as most of the people are coming from villages and poor socioeconomic status. And even here in Kilimanjaro in some of the district which are heavy mountains areas, we feel like we have under screened.

And you have to think of that if we be having resources later, because when we did this screening site in the district hospitals they're in the lower part, not in the mountain, but these many men are living in the mountain area, so they could not come down for screening.

So we are thinking of maybe going later on into the mountain and making sites so that we can screen these people also. And we suggest if possible to repeat the PSA screening and possible trucut for people who are having screening. We might have just missed some of the people who might be having, it depends on the biopsy and all, but also it might be a starting point.

And then they can a marker or an alarm where they can progress to the disease. And we think that's quite important, actually we have been doing it. We added a component of monitoring for complication after trucut, which we thought that is important. Some could say maybe they have signs of UTI and some could... So we have tried to support them.

Whoever comes with complication doing culture, seeing they have urine tract infection, give them treatment or counseling. And some of them might have maybe bleeding after it then you find that are those with prostate cancer and support them.

So we thought that with this patients` and poor access maybe to treatment and whatever, we might need also to do a kind of clinical trials for prostate cancer screening as we are doing for HIV, for tuberculosis. And might be a supportive of understanding maybe what kind of treatment might be very useful in this population for prostate cancer.

Especially those we are getting from the community, we expect that they might be not advanced much. Although some of them who have noted that they have advanced disease. And this is how dissemination again, I can finalize with this. This is in Arusha region where the newsletter had publicized about our work.

One of our colleague, Dr. [inaudible 00:24:34], who is in Tanga now screening had been interviewed and talked about the prostate cancer. But also this is a poster which is talking about high prevalence of prostrate cancer in Northern Tanzania, a call for scaling up screening program. Yeah. So this is what I can share for our preliminary because we're in the middle of the way. So thank you very much.

Charles Ryan: Oh, that's really terrific. A very ambitious project. And I think you're already seeing positive results. As I hear about programs like this and the headline you just showed unearthing men from hiding, I think about prostate cancer, but I also think about other medical conditions that you might be able to pick up if you are bringing men in for an evaluation of PSA tests.

And even those who don't thankfully have prostate cancer, you may be able to identify hypertension or other factors. Are you seeing that type of an effect so far, other diagnoses of people who just haven't seen a doctor in a long time?

Blandina Mmbaga: Yes. We do see it. I can give an example of one case which Dr. Nicholaus speak on the first day. And he found a man with a very high blood pressure, 190 over 130 almost. And we do have also a priest kind of a college here at KCMC where they come and when they say for four months and at least they came to the center also for screening.

And he learned that he's coming from KCMC and for the priest center with that higher result, then he jumped in and told me that I found a person with a very high blood pressure who doesn't know and doesn't to use medication. So we had to link him with the medical physician so that he can start care and start getting medication.

So those incidental findings are there. And the other thing we found, of course, most of the people are obesity, and we could see a little bit of even the correlation with the prostate cancer, maybe at the end, but we've started seeing the highlights.

And so those are things we really want to see and see, because now noncommunicable disease is a threat and this comorbidity are common to undergo together because of one thing weakens the other and reducing mobility causing the other now noncommunicable disease. Yeah.

Charles Ryan: I think that's a really important observation and the idea that prostate cancer screening can save lives not only from prostate cancer, but from other conditions as well. So I think that's interesting. I was also intrigued by the finding that 19% of patients had a high knowledge of prostate cancer.

I would imagine that over time as you do this year in and year out were going to see that number go up because I'm almost certain that the word of your work will spread through the region and that will improve. I was going to ask about family history and how many patients who you talk to know if they have a brother or a father who had prostate cancer. Is that something that people tend to know in your region?

Blandina Mmbaga: Yeah. I think especially in the case of prostate cancer, yes. Some people tend to know because they might have their relatives who died with prostate cancer. We had that question within our questionnaire and maybe while we are discussing we can get that number, because our statistic is sitting behind me.

Charles Ryan: Very good.

Blandina Mmbaga: I can see her pulling the computer and wanting to start.

Charles Ryan: So if I could I question for Dr. Ngowi. From a urology perspective, when you have identified patients and we can talk about the Gleason score, but are you able to identify patients who are undergoing local therapy and have the number of patients having local therapy gone up, whether it be radical prostatectomy or other? I think that that's one of the key metrics here for success would be to identify patients who are curable with therapy.

Nicholaus Ngowi: Yes. Thank you so much for this quite important question and actually the challenging part of it, as Prof. Blandina has said, that some of these patients, they have challenge when it comes to investigations and treatment because sometimes you need to investigate thoroughly to know the stage of the disease before you plan the treatment.

So what we have found is that we have very little number of patients who afford treatment. And most of them, they said, "Want to go home and prepare ourself. We'll come back." So they never show up. Sometimes we call them, but they usually say, "Okay, we are still looking for money."

Of course, it may be true that they have financial problem or probably they're in the denial. That's why we keep on following them up and we counsel and counsel, because we never know what is happening to their minds. But so far what I can say, we have very, very few patients whom, I mean, whom we have offered thorough treatment.

We have one patient whom we did radical prostatectomy who is from the screening. And I can say probably it was a little bit unfortunate that although we did this CT scan, we did CT bone survey together with CT abdomen with pelvic, which were almost normal except that there was localized disease.

Intra-op we found involvement of one of the seminal vesicle, and pathologists also confirmed the involvement of the seminal vesicle and this patient after we discuss with our colleague in pathology, I mean, in oncology, we saw the best option is to start the patient on androgen deprivation therapy and then he'll get also radiation therapy and then continue with ADT for least two years.

Yeah. We have two cases which also they had, I can say moderate, I mean, intermediate risk disease. And in our discussion, we thought these patient could benefit from androgen deprivation therapy for two months.

And then they can go for radiation therapy and then continue with androgen deprivation therapy for another two years. So these are the cases which I think they can be cured of the disease. The rest, which we had, they fall under palliative care.

Charles Ryan: Palliative care because they have metastatic disease?

Nicholaus Ngowi: Yes. They had metastatic disease with PSA more than 100. Some they had already obvious osteoblast changes on plain X-ray because we sometimes start with a plain X-ray once we suspect metastasis, we just start with a plain X-ray because it's very cheap and our patient, most of them they cannot afford. So we start with something cheap.

So obvious metastasis on plain X-ray, so we thought there's no need to do any CT skeletal survey. And therefore we start a patient on ADT, androgen deprivation therapy, which most of the time here, of course, although with the metastatic disease the best option is to do surgical castration.

I'm not sure in your place, but in African settings, it's quite challenging for a man to accept his testis to be removed. So sometimes they want to go towards a medical castration, of which also they cannot afford because I mean, this Zoladex, for instance, it costs around, how can I convert this to USD? Prof. Blandina will help me. It's around 300,000 T shillings. A monthly injection-

Blandina Mmbaga: Yeah. 120 USD.

Nicholaus Ngowi: 120. That is a monthly injection. So you can imagine somebody needs this for probably the rest of his life, is quite tricky. So I remember one patient refused surgical castration, cannot afford medical castration. So he went home.

Charles Ryan: We have similar challenges in the US with people accepting surgical castration, which of course is the most cost effective way. Of course it's irreversible. So that highlights an ongoing challenge in your country.

I think for those gentlemen, you have clearly identified some and probably will identify more patients who you'll be able to cure because of your program who otherwise would end up coming to see you in a year or two with advanced metastatic disease.

So that's really encouraging. And for the men with metastatic disease, they can go on treatment and their life will be prolonged. We may consider it to be palliative treatment, but I consider that to be life prolonging treatment.

And of course, as you know, a person who has metastatic prostate cancer, who does not go on androgen deprivation therapy is going to have all kinds of complications and problems. Whereas the androgen deprivation therapy will prevent those complications and prolong life.

I have a question now for Dr. Mremi about the pathology that you're seeing. It was interesting, I think there were 67% of the cases were high in intermediate grade. And it'll be interesting to see what happens with the pathology over time and whether or not as you repeat this process year in and year out, whether you tend to trend towards earlier detection and lower grade disease.

Are you surprised by the findings of what you're seeing in terms of the high intermediate grade numbers or what are your perspectives on the pathology that you're seeing?

Alex Mremi: Thank you Dr. Ryan. So most of the patients whom we see they have hybrid tumors. So I think leave alone this project, on the clinical perspective, most of the patients we see they are high grade. Very minimum, I mean, intermediate, but majority they are of high grade.

So even in the screening naturally I saw intermediate increasing, but on the average putting together, majority of the patient they come with high grade. Of course I understand in the study, there are some patients who had slightly elevated PSA and then the biopsy came to normal.

I think Nicolaus will agree with me that this will follow with biopsy in the near future because they have not so much elevated PSA. However, their biopsy is not malignant. So we are planning for some time to follow this patients. Yeah. Thank you.

Charles Ryan: Is there anything that I didn't ask and I should have that you would like to speak to before we conclude, or do you feel you've said everything you want to say?

Nicholaus Ngowi: Yeah, yeah. Maybe I wanted to say something more.

Charles Ryan: Sure.

Nicholaus Ngowi: No. One of our objective was to look at the correlation between PSA and prostate cancer, but you also want to look at the correlation between PSA and the Gleason score, right? So quickly when you look at the, I mean, PSA and Gleason score, we found that there's no really correlation.

Although in some studies they have shown there is a very strong correlation within PSA and Gleason score based on some, but quickly when you look at it in a preliminary way, we found there's no real correlation between the two. This is what I wanted to add.

Charles Ryan: Interesting. Is it perhaps that we're having higher Gleason scores perhaps having lower PSAs than one might expect? You're detecting high Gleason disease in low PSA patients, is that what you're saying?

Nicholaus Ngowi: Yes. We found that even with a low PSA, the Gleason score we find maybe it's at the intermediate.

Charles Ryan: I see.

Nicholaus Ngowi: It is very much surprising. Also, we had a discussion with our colleague oncologist. He was also very much surprised.

Charles Ryan: Yeah. It could be, of course, more poorly differentiated disease makes less PSA. We see that sometimes as well. Are you banking all of the pathology that you detect here and creating a tissue microarray or some sort of tissue bank?

Alex Mremi: Yeah. So all the trucut biopsy from the postate, we archive them. I think this can be also used for future studies. Of course though we don't have the, I mean, the patient's consent for the future study, but as long as they have consented for the current study, I'm sure we can request for waiver from the IRB.

I want us to say that we have the IRB, I mean, we have the archive for all cases which we collected. I think the same applies to blood-

Blandina Mmbaga: The serum.

Alex Mremi: .. the serum which we use for PSA.

Charles Ryan: One factor to consider would be looking at the genomics or the genetics of the tumors down the road, determining if there are common mutations that are present in your population, et cetera. So great that is being saved because it opens up the opportunity for more work down the road.

Alex Mremi: Sorry, maybe additional point to Nicolaus. I think one thing which I also noticed from this study, what we call elevated PSA might be subjective or relative rather from in the Western countries to black Africans. I think it's not unusual in our setting for a patient with elevated PSA, will just have a benign prostate. I think maybe this is one of the findings which we have observed.

And also one thing is that we are increasingly seeing patients with invasive tumor at younger age. I remember thinking before this study, myself and Nico, we wrote some case report involving a metastatic prostate from a patient I think under 40 or somewhere around.

So this is one of the findings which we see patients younger age, aggressive tumor with the so much elevated PSA. However, PSA below 20 sometimes might be benign. Though as I mentioned, we are following them up to see if they will be benign or they will change. Thank you.

Charles Ryan: Important observation for sure. And certainly something we'll want to track about younger patients. Of course, there is a distribution for this disease and we do see, in all sites, we will see unfortunate young men with high grade and metastatic disease.

Excellent. Well, I think that what we see here is the start of a really great program. You already have great preliminary data. You're already presenting your data and we can already see what the challenges are for you and your center and how we might be able to partner to work together to address some of those challenges.

So I want to congratulate you again on your receipt of this award and encourage you to keep in touch. And hopefully we will hear results down the road of even more screenings. And while we don't like to see more positive biopsies, we know that screening leading to a positive biopsy is potentially preventing an advanced case from presenting later on.

So thank you so much for your time today. Congratulations on your award. And we look forward to seeing further results.

Blandina Mmbaga: Yeah. Thank you very much.

Alex Mremi: Thank you Ryan.