The Medical Innovators Interview with Professor Shingai Mutambirwa
Sequencing the Black African genome, the urologist shortage in Africa, and making friends with cancer… It’s all in our new Medical Innovators interview, with Combat’s Guy Cooper in conversation with Professor Shingai Mutambirwa, chief of the Division of Urology at Sefako Makgatho Health Sciences University, in Pretoria, South Africa.
Born in Zimbabwe, Professor Mutambirwa grew up in Canada where his parents had relocated to pursue their postgraduate studies. He returned home in the 1980s to study medicine and graduated cum laude in 1988 from Godfrey Huggins School of Medicine – the youngest ever medical doctor to graduate in Zimbabwe at the time. He was inspired to enter urology by Zimbabwe’s first urologist, Dr Alex Danso, who encouraged him to pursue his MEd (Urology) at the Medical University of South Africa.
His passion for research and desire to “make things happen” have resulted in his involvement in many innovative projects, from being a founding member of the Prostate Cancer Foundation of South Africa (PCF) to heading a review board for South African Guidelines for Enuresis under the Enuresis Academy of South Africa.
He is a peer reviewer for the Journal of Urology (AUA), African Journal of Urology and Hindawi online publications, heads the medical and scientific advisory board of the PCF and the academic committee for the South African Urological Association (SAUA), and is a member of the Continence Association of South Africa (CASA). He also developed a technique that uses skin glue for circumcision and has completed 3000+ cases – the most worldwide. With Southern Africa’s prolific HIV rates, this has no doubt made a significant contribution to reducing rates of HIV and STI infections. Professor Mutambirwa has also been prominent in creating awareness about men’s health issues.
Professor Mutambirwa, tell us about the areas of specific interest that you’re working on today.
In sub-Saharan Africa, most of us have to do a lot of general urology because there’s such a shortage of urologists. Between North Africa and South Africa, there are literally about 90 urologists for all the countries in that area. Some countries only have one or two, and they’re doing a great job. But the problem is that you can’t just focus on one thing. Fortunately for South Africa, we do have almost 250 urologists for 60 million people, so we’re relatively well resourced. But most of our urologists are in the private sector. So about 80% of the South African population is serviced by the public sector. Yet only about 20% of the doctors work in it.
So my interests have to be balanced with the socioeconomic situation in South Africa and in Africa in general. And I do a lot of work with colleagues outside of South Africa as well. But my main focus has always been on prostate cancer. We’ve got a big genetic assessment that’s been going on – our patron was the late Emeritus Bishop Desmond Tutu. He let us sequence his genes with our colleagues mainly from Australia, the Garvan Institute, Vanessa Hayes and others.
And Desmond Tutu’s was the first Black African full genome which has been sequenced and we’re really quite proud of that. We’ve had a couple of insights into that since then. And that sparked part of my interest in cancer and oncology in general. I’ve got my unit and we’ve got different units which deal with paediatrics and female urology, and we’ve got a couple of clinics which deal with male urology. But my main focus now is oncology, because of the rest of my colleagues and because I’ve got a great team. They free me up so I can do a lot more oncology and they can get on with the other stuff. But when it comes to oncology, I think it’s such a big issue.
In Africa, we’ve actually got lower incidences of a lot of cancers, including prostate cancer and bladder cancer, than other countries. But the point is that our record-keeping is not very good. So one of the aspects that we’re doing besides the oncology is being involved with cancer registries for South Africa, which we’re going to try to roll out to some other parts of the Sub-Saharan African region. But if you were to pin me down after all that waffle, I’m into oncology and I basically like all oncology. As one of my favourite authors, Tom Robbins, said in one of his books, Half Asleep in Frog Pajamas, “You mustn’t fight cancer – you must become friends with cancer so that you can actually control your friend.” So I think that’s one of the aspects that we’re trying to do by involving ourselves with oncology.
How are you treating prostate cancer in South Africa? Many places where the British hand of colonialism has been in the past tend to use brachytherapy. It’s very popular over here and in Australia, Canada, North America and the UK, but I don’t see it anywhere else. Are you guys doing brachy?
Yep, we are. When I first started in urology, about 80% of our patients were de novo metastatic when we met them. And so it was basically orchidectomy, orchidectomy everywhere. We’ve improved it bit by bit, with more screening through our local Prostate Cancer Foundation, which I’m one of the founding members of. We’ve encouraged a lot more screenings. In the state sector we’ve lowered it to about 45% of our patients now presenting with metastatic de novo. It’s still much higher than most of the countries in the so-called developed world compared to us. But it has improved.
But our private system is probably even more efficient than your NHS system to be honest, because technically, you could get into a urologist’s office today, you could be seen without an appointment, you could get a biopsy, you could get diagnosed, and you could be treated within a couple of days. And that impacts a lot on how the treatments go in our private sector particularly, because it’s pretty easy to get both of these things done.
Fortunately or unfortunately, for the majority of our prostate cancer patients, we’ve got a lot of Black African myths and feelings about things and being cut is often a bit of a taboo. So the idea of not having to be cut to cure a cancer has pushed us to have about 80% of our patients with localised prostate cancer getting brachytherapy plus or minus external beam, plus or minus androgen-deprivation therapy.
But there’s still a good number that get radical prostatectomies and we do have robots in the country. We’ve got five, going on six. Our unit in Pretoria is going to get, I think, the seventh unit soon. And I think it makes a big difference when it comes to encouraging patients to get treatments. With prostate cancer, there’s always the argument about radiotherapy versus surgery for localised prostate cancer. We’re never going to have randomised controlled trials about this. The short answer is that yeah, I don’t think it makes that much of a difference, regardless of which one we do. And it’s a matter of choice and discussion with your patients, which I think is the most important thing when it comes not only to oncology, but generally with patients.
What’s happening with cancer screening? You can’t turn on a sports programme in the UK without seeing some prostate cancer awareness messaging, which is great. My father had prostate cancer, and my grandfather, so I know enough about genetics to understand it’s a good thing that people are talking about it. And everybody is encouraged to get their PSA done from the age of 50 upwards. What does it look like in South Africa?
Our guidelines were developed by a group of us many years ago for the Department of Health, and we actually came up with 40 as the starting age for doing PSA screening – partly because we’re high risk, but also some of the data we have has shown that we do have much earlier presentations of these prostate cancers and they are more nasty, although there’s a lot of variation.
I think people often see Africa as one paint stroke of everything. But the reality is that we’re actually obviously genetically different in so many different ways. When you consider that Black Americans are actually mainly of West African origin and we’ve got data to show that East Africa is different from West Africa, South Africa is different from East Africa, and even within South Africa, we’ve got huge variations in treatments and assessments.
For example, we know that the Venda tribe in the northern part of South Africa are more likely to develop prostate cancer. But they’re also more likely to be able to get long-term suppression from androgen deprivation compared to our Swathi cohort, which is a bit more southerly. So I think it’s a big thing. Through a number of associations, including the fact that the Department of Health is particularly interested in this, and through the Prostate Cancer Foundation, where we have a great CEO, Andrew Oberholzer, who’s doing a lot of good work, we have been pushing a lot for more people to get PSA screenings.
And maybe you note that I’m not mentioning digital rectal examination [DRE] because that’s actually one of the biggest hindering factors we’ve got when it comes to preventing African men from getting tested. We had an assessment through our department of psychology where we showed that about 85% of our patients were unwilling to come for prostate cancer screening, mainly because of DRE.
There’s a big push in the UK at the moment on publicising the PSA, which is just a blood test. So you don’t have horrifying concerns about some large, sausage-fingered gorilla of a urologist wandering across the room towards you. I think that’s certainly something where patient education is important.
And we know that DRE has never actually been validated as a screening anyway, but PSA has. So I think the guidelines now say it’s not actually necessary.
If you know from anecdotal evidence or from registry evidence that certain groups of people have a genetic predisposition for how prostate cancer affects them and how they can outlive it, what’s the next thing? You have your Desmond Tutu genome – I have this picture now of a Jurassic Park with a 70-foot-tall Desmond Tutu in it – but you are doing some work on mapping the genome of African men. What does that look like? Are we going to find some alleles that we can turn on or off for prostate survival? I did an intercalated BSc in genetics at medical school, but this is probably the most I’ve discussed about it in 20 years. So remember I’m essentially an orthopod and keep the words simple and short!
That’s OK!
So are you going to splice a bit of gene off that protects us from metastatic prostate disease?
Yeah, great question. I always tell my residents that if you’re going to be doing anything, you’re setting up a guideline or whatever, there must be some benefit at the end for the patient. And currently, to be honest, we really don’t know. That’s the biggest issue. What we have shown is that there is such heterogeneity amongst all the different ‘tribes’ and obviously interpersonally as well.
We have a patient who’s a Khoisan, essentially a bushman – from the people who used to live in the desert in the Kalahari and the West Coast of Africa. The genetics of this particular individual have so many different predisposing genes that could actually increase his risk of prostate cancer. One of the things we’re looking at is whether this translates into shorter life expectancy, because we know there are other confounding aspects. For example, if you’re living on the land in the sun for a couple of decades, maybe that’s causing the problem. So I think we don’t really know what we’re going to do with most of the data so far, but it’s important for us to get it so we know what’s happening with our patients.
When they first sequenced the human genome in the Crick Institute here in the UK, there was a mad rush to get it all down on paper. But to my relatively untutored knowledge, they’re still in the same position, in that they don’t know what to do with it. Now is that where we’re going, that in 20 years’ time we’re not going to have urologists or surgical oncologists – we’re just going to have geneticists turning things on and off?
In some ways, I think we’re heading in that direction. I think with artificial intelligence particularly, which is a big interest of mine as well, we’re progressing very rapidly, far faster than we thought we’d be as far as getting information out there. And I think it is eventually going to impact our treatments. A couple of years ago at one of the ASCO meetings, one of the oncologists stood up and said, “In ten years, you urologists won’t have a job”, and we were all laughing. But when you consider now that, for example with AI, when you look at radiogenomics, you’re looking at pathology, and we’re all going to be having to readapt. I don’t think we’re going to lose our jobs. We’re still going to be necessary where there’s compassion, empathy, interaction and discussion that needs to come from a treating physician.
But I think that if we don’t adapt, we’ll die. It’s going to be a big issue when it comes to treatments for prostate cancer in general because there might just be medications eventually that we’re going to be using. For example, we’re already starting to introduce some of these androgen receptor pathway inhibitors upfront, including some of the radiopharmaceuticals that we’re using before we do a radical prostatectomy on the patient. I think it’s going to make a big difference.
And then on top of that, the robots, which we’re all involved in, are very expensive to use at the moment, but the point is that automated robots are on the horizon. Some of the data that we’ve done and videos that we’ve supplied to some of the companies that are developing these robots, that’s what the long-term aim is. So I think we’re not obsolete – we’re not dinosaurs yet as teaching physicians. But I think we do need to adapt and find new ways to interact with our patients.
Which robot are you getting at your centre?
I’m not going to mention the name, but it is the commonest one. Mainly because the head of surgery there is very convinced that the other ones are not well tested yet. But the point is that I think they’re all very good.
Yes. There are a few kicking around now, and not just Da Vinci. Here in the UK, there’s a very interesting one – Versius – from CMR Surgical that is thought to be very good, and then Medtronic have the Hugo RAS. It was originally thought that robots were going to be for deep intracranial work and all this mad stuff in the specialties, but you guys now have them for bladders and prostates. How has that happened?
I don’t know how we got to this position. The mainstay of GP work, for example, is actually urology – it’s STIs, it’s infertility, it’s the bladder infections – so it’s actually super-common for GPs. But when it comes to urology, we used to think that no, we were pretty much meat and potatoes guys. But I think after the advent of the radical prostatectomy, that’s where we started to look more at the ability for us to actually make a difference with this.
And then I think we were just early adopters. We decided that urologists like the idea of doing these procedures minimally. And I think we’ve progressed quite nicely, but we’re not at the forefront. I know that the obstetricians and the general surgeons also do massive amounts of robotic work. But the radical prostatectomy is pretty much the poster boy when it comes to robotic surgery now. And when you’re looking at prostatectomies and cystectomies as well, it’s a huge thing, and then it makes a big difference.
Ham-fisted radical prostatectomies paid my mortgage for five years! I was the international guy for the now departed American Medical Systems with their penile prosthesis and bladder valves. So yeah, I haven’t seen a good paper that tells me a robotic prostatectomy is better for nerve-sparing than a really good open surgery or lap surgery. Is it just a toy?
No, it’s not a toy. But when you get down to the granular part of the data, you’ll find that it’s mainly about the learning curve and the volume of the surgeon. I think if a guy was doing one robot every six months and I had a prostate cancer and another guy was doing open six times a day, I would rather go for the open. But I think there is pretty good data now to show that the robots do make a big difference when it comes, not in general to oncological control, but definitely to the amount of blood loss and to the length of the hospital stay.
Does this translate into a benefit when it comes to cost? Because of course there are massive costs associated with robots, although they’re going to come down now with all these new systems that you’re talking about. But I really it’s the future. I think I’m on the downward curve in my own training. I’m not going to be going through the learning curve of doing robotics myself, but all my residents have to go through the robotic platforms and laparoscopy.
And then – to add insult to injury – we have to look at the rest of Africa, where there’s a large burden of disease but where they’ve got no access even to an MRI or to sometimes even to much more basic stuff. So we have to balance that. As I said, I think it’s a socioeconomic thing as well as the fact that we have to concentrate on making sure that oncology is addressed.
I think the benefits – not only in terms of precision and repeatability, but the benefits in terms of blood loss, hospital stay, lack of surgeon fatigue – all add up to a better picture. But Europe is awash with robotic options for cancer surgery. There are over 100 in the UK alone. So it’s very much a case of two worlds.
I like the many ways that the British system has adapted – you have to do a specific number of cases and be authorised to do procedures. I think that’s probably the way of the future.
We can’t all be doing everything. We’re basically all generalists, but being a generalist does not make you a better urologist when it comes to specific metrics. The last time I closed a bladder exstrophy was maybe 15 years ago, because it’s not really my forte. I’ve trained guys who now are doing pediatric urology and having much better outcomes than I ever had when I was doing these things. So I think it’s important for us to adapt as we go along and know our limitations, including about costs and access.
Let’s go back one organ to the bladder. Bladder cancers are perhaps a bigger problem in African countries because of bilharzia-related bladder cancer, and yet we don’t do anything any different than I did 30 years ago in North London. Why is that? Or am I missing out on something? What’s the next thing coming there?
We know that smoking is the biggest cause of bladder cancer. But bilharzia is huge in Africa, although it has changed a little bit with massive amounts of prophylactic treatment. One of the interesting aspects we are also investigating is trying to see whether bladder cancers developing with a predisposing bilharzia will respond differently to some of our bladder-cancer treatments. Again, the biggest issue for our population in the public sector is that the vast majority of patients are going to come in with muscle-invasive and big muscle-invasive cancers. Look at the Egyptian data showing that if you can palpate a bladder cancer above the pubis when you do a rectal examination, you shouldn’t even be operating on that patient. We don’t get those.
I told my residents when we’re looking at the data, that when you say muscle-invasive, it’s not like ours where we can actually feel the mass there. In Europe or in America, it looks like a tiny little thing on the bladder, it’s resected and then the pathologist says, “We can see there’s some muscle-invasion.” That’s not the sort of thing we’re looking for, even though I think we still need to bring up the facts about social changes, stopping smoking, all that sort of stuff. That’s going to make the biggest impact. But I think we need to get to the point where we can actually pick up bladder cancer super-early, even if it’s muscle-invasive.
So I think that’s the biggest issue. We don’t really see much non-muscle-invasive as a general rule. But in the private sector in South Africa it’s actually extremely common. And I think one of the biggest problems we have for bladder cancer in the private sector is that we have a lot of discordant treatment guidelines. And, just like everywhere in the world, we have problems getting BCG.
There are also so many new choices to treat non-muscle invasive bladder cancer. I’m excited by a lot of the trials we are involved in with – whether it’s BCG alternating with chemotherapy, your HIVEC® system, or other thermal chemotherapies. I also think that alternating docetaxel with gemcitabine is a big thing. But I’m even more excited by some of the data coming out with intravesical hyperthermia plus gem/doce and gemcitabine.
We work with Professor Mike O’Donnell at Duke University– I did one of these with him. He described himself as the mad scientist or the mad cook of bladder cancer, because he’s mixing up all the different chemotherapy regimes. And gem/doce is where his money is. I think from a point of view of usability, affordability, access and all the things we discussed, gemcitabine and docetaxel are two cheap and readily available drugs. When we were at the Namibian Oncology Centre, they had a fridge full of KEYTRUDA –
You shouldn’t be mentioning trade names – it’s pembrolizumab [laughs].
– Of course, yes. They’re just making these drugs up so that I can’t pronounce them. We have atezolizumab, we have pembrolizumab. I listened to Tom Powell’s talk about these things and he runs them all off and I understand perfectly. And then I walk out of the room and 10 minutes later I’ve forgotten it all again, but OK. So urinary biomarkers, is that where we’re going? Because especially for your later presenting patients, it’s rubbish. Half the bladder-cancer patients we see in Europe are coincidental findings from people turning up with stones or haematuria. So we have PSA blood tests for prostate. Well done, we’ve solved that problem. What are we going to have for bladder cancer? What’s the next thing?
Well, fortunately I’m not the only one who’s doing this. I think there are a couple of important things. First of all, it’s the epidemiology and the fact that we need to encourage better lifestyles. We also need to pick it up earlier, and particularly for females – that’s a big issue because they have poorer outcomes for bladder cancer, partly because we always think it’s just UTIs when it’s not.
But I think the biggest thing for me besides the therapies, is about biomarkers. I really think that’s the future. And the biomarkers are not just about urinary samples, not just about blood. It’s about AI, radiogenomics, the way we can map the cancers, whether we are using specific things like blue light or narrow-band – which I think is a much easier technology to use than blue light. We don’t have blue light in South Africa, but we know it’s FDA-approved.
So I think biomarkers and whether it’s muscle-invasive or non-muscle invasive, picking it up simply and making a decision about whether you need to go straight for radical therapy or not – these are the things that are going to make a big difference for our patients. Again, we have to look at cost, we have to look at accessibility, we have to look at skills. But I think it’s a huge thing.
But I think once we get to the non-muscle invasive part, although BCG is still the gold standard, there are so many things on the horizon that are so important for us to recognise. We haven’t mentioned mitomycin C yet because we’ve talked about gemcitabine, but it’s very scarce, it’s very expensive and it’s got some nasty side effects sometimes as well. So we have to balance all these things with the chemotherapy and treatment cycle.
You mentioned immunotherapies for non-muscle invasive patients who are BCG unresponsive. But when you consider that per milligram, these medications are 5,000 times more expensive than gold – I think that came from an ASCO meeting – how are we going to access that? And you’ve got side effects as well – because it’s not without side effects, it’s a systemic therapy. I think some of the intravesical versions of using immunotherapies are also very interesting.
I think some of the things, like for example, the Adstiladrin and the Vicinium and the Abcam drugs that I’m using Abcams with the pseudomonas toxin, those are big things as well. But again, we have to remember that all of these approvals are based on specific trials using specific patients. And I think we have to recognise that when we’re looking at non-muscle invasive, it’s CIS, it’s papillary, it’s the type of cancer, it’s the cancer’s position.
For example, if it’s an upper tract, we know there’s a lot to do with Lynch syndrome. There’s a lot more FGFR, so there might be better things for upper tract. And, of course, the histology – they’re also going to make a big impact, because we get a lot of squamous – although it depends on the percentage of squamous that you get in non-muscle invasive as well. But the point is that it will probably have an impact on how we treat our patients, and there are so many options.
For your non-urothelial tumours, do you do cystectomy for everybody, whether it’s bilharzia or squamous or whatever? Or are you looking at some of the less radical options?
We have a bit of a struggle to get patients to accept cystectomies. And if I had bladder cancer, I would have a very big problem having a cystectomy as well. So I think it’s important that we have that discussion with our patients. And if it’s not standard urothelial cancer, I don’t think there’s very good data to start doing “conservative” therapies. But I think that gives us an opportunity to actually investigate trials. Like for example, using intravesical hyperthermic chemotherapy in patients with a highly, highly squamous cancer to see if the patient refuses cystectomy, which the vast majority do. And then we can then have a discussion and we can actually get data to make decisions on finding ways of protocols, how we can decide which treatment is most appropriate.
When you look at the preclinical data – for example, with electromotive and with intravesical hyperthermic chemotherapy – it actually has good data to prove that it’s just about getting the approval trials done eventually. There are so many opportunities for us to actually use them in different phases. But we have to balance them with the cost and accessibility, because companies are not going to be spending money on things which they’re not going to make a profit eventually on. So as clinicians and researchers, we also have to look at finding ways of getting better outcomes using various markers, including biomarkers, to make a decision on our treatments.
OK, I’ll switch it around a little bit now. We spoke a bit about the future and about whether it’s just all going to be geneticists and AI-powered robots. I’ll throw you the keys to the DeLorean and you come back in 2050 to your department. What does it look like? Is there anybody there?
Oh, Back to the Future! Interesting question. In South Africa, we call them sangomas – witch doctors. They can predict the future. I would predict we are going to be in a much better position. Our training is going to change. Our jobs are going to be more integrative, as part of multidisciplinary teams, particularly with oncology, but also with other aspects of treatment. And we’ll be developing newer ways of treating patients.
Again, it’s about becoming friends with everything. We have to make sure we don’t just consider everything as an enemy, fighting things all the time, saying “This is bad, this is good”. In the future, we’re going to become much more integrated, not only with AI but also with our different people, about what we can do, how we can help each other, how we can improve the outcomes, and how we can benefit, even from trials, to make decisions on what we’re going to be doing. So I think it’s very positive.
We are going to have to change our ways. Unfortunately, I’m an old dog. I think you’re also an old dog, so we might be out to the pasture by then. But with longevity increasing, we’ll probably be around and we might be influencing some of these policies. I think we need to make those changes and not just on dogma. Like, for example, when it comes to the trials for non-muscle-invasive bladder cancer, the FDA took a very good decision to base some approvals on phase two trials, because it’s difficult to have comparators. So we also have to start adapting to make things better for everybody.
I think so. I think medicine will become more personalised and genetics will play a huge role. They’ll heel-prick a newborn baby, and that drop of blood will give the menu of diseases and cancers you have to look forward to and what you can do to combat them. Professor, thank you very much for your time – it’s been a pleasure.
Thank you for the opportunity. It’s always great to talk to a fellow researcher about the stuff they’re doing and some of the innovators.
I’ve been called many things, but I’ll settle for researcher! I’ve done quite a few of these interviews now with urologists and surgical oncologists, and similar topics keep coming up. What will it look like in the future? How personalised will it be? What will the biomarkers be? What, genetically, can we understand better than offering the same treatment for everybody? Let’s see if we can boot this hugely under-researched, underserved area along a little bit.
It’s exciting. That’s the most important thing. We know innovation and changes are coming. And we follow them, vet them and find new ways we can deal with these things.
