’If patients aren’t fit for or don’t want to have a cystectomy, and prefer bladder preservation, HIVEC is a very good option for them’

Could developing innovative day-case pathways help the NHS deal with the growing pandemic backlog of cancer treatments? How can we better support patients through their bladder cancer-treatment journey? And what is the role of HIVEC® (hyperthermic chemotherapy) in managing the recurrence of high-grade, non-muscle invasive disease? These are all issues we’re discussing in this month’s Medical Innovators Series interview with Helena Burden, consultant urologist at the Bristol Urological Institute, one of Europe’s busiest oncology centres for cystectomies and prostatectomies.

Our Medical Innovators Series investigates developments in the medical and clinical worlds with the people right at the sharp end. If you’re a fellow medical innovator who would like to be featured, please get in touch and we’d be delighted to speak with you.

Great to meet you, Helen – tell us a little bit about yourself and your areas of interest.

I’m a consultant urologist in Bristol and I’ve been there for about five years. We’re a big tertiary referral department. My specialist area of expertise is non-muscle invasive bladder cancer [NMIBC], and I also do a lot of core urology and diagnostics. We work in a team of three consultants all specialising in NMIBC and our unit is quite unique in having specialists in both NMIBC and muscle-invasive bladder cancer. It means that we can lead the way for bladder cancer in our hospital, in a very innovative and cohesive unit.

What does an average day in theatre look like for you?

Ha! I thought you were going to ask me about what an average day looks like, rather than an average theatre day. Because, quite interestingly – and people often find this surprising – surgeons don’t always operate every single day.

Our average week has some diagnostics, clinics and theatre. However, most of my lists are a three-session day – starting quite early in the morning after I’ve taken the dog for a walk, finishing quite late at night and hopefully seeing the children before they go to bed. Although I still do some core urology, my theatre days mostly revolve around NMIBC, either new diagnoses or recurring disease. Bladder cancer is a disease with a high recurrence rate. A lot of our patients are long-term, so we do get to know them quite well.

There are several different ways of doing TURBT [trans-urethral resection of bladder tumour] at the moment – what’s your process? Are you using augmentative visualisation systems? Are you using something clever?

Well, augmentative visualisation is very clever – it’s enhanced TURBT massively. We do bipolar PLASMA TURBTs with narrow-band imaging to enhance the visuals. We use that both in the diagnostic flexi suite with our HD scopes and when we get to theatre. We tend to do mostly fractionated TURBTs, although the smaller ones we will do en-bloc. Our patients then all get one shot of mitomycin, as per the guidelines, after the operation if they’re a new diagnosis, as standard.

We are possibly doing things differently from some other units, because we have a very high day-case TURBT rate. That was highlighted in our GIRFT [Getting It Right First Time] reports. We’ve got a very efficient multidisciplinary day-case pathway.

I can see the benefits of that in terms of patient stays and patient morbidity being reduced, and I can see the financial benefits because your in-care patient costs are lower. How are you doing it, and why aren’t other people? Why are you leading the way?

It goes back a few years. When I was a registrar working in Bath, they lost their specialist urology ward, so I assisted my consultant, Chris Gallegos, in setting up a day-case TURP [trans-urethral resection of the prostate] pathway. One of my colleagues, Anthony Koupparis, also set one up in Bristol about the same time. Since I became a consultant in Bristol, we have extended the day-case TURP pathway and have also included our TURBTs.

It’s innovation through necessity.

To some extent, yeah. The world is changing, and it’s changed significantly over the last two years with the devastating effects of the COVID-19 pandemic. Anyone wishing to get any of their operations through theatre at the moment, to make theatre more efficient, increase flow and reduce bed base has to look at innovative ways of thinking – like day-case pathways. We were quite lucky to be already doing these before COVID. So we haven’t really had a problem, particularly with getting the TURBTs through. I believe many other hospitals started looking at day-case pathways during COVID to get their caseload working again.

The technology we use has also helped massively with our day-case pathways, along with the rest of the multidisciplinary team that make it possible. Part of the key to our day-case pathways is PLASMA technology – you get such better haemostasis with that for TURBTs and TURPs than you would with monopolar. It also helps that we don’t then need to irrigate afterwards on a routine basis. A lot of other places still do and that necessitates patients being in-patients. What we tend to do instead is give them self-irrigation at the end of the procedure, then fit them with a two-way smaller catheter.

Anyone wishing to get their operations through theatre at the moment, to make theatre more efficient, to increase flow and reduce bed base has to look at innovative ways of thinking – like day-case pathways.

What has the pandemic impact looked like for your unit over the last 20 months – and counting?

We don’t have a huge backlog in Bristol. I know other centres aren’t in the same situation. I think all hospitals would have been different, depending on how they’ve been hit with COVID. We were quite lucky in the southwest in general, in that we weren’t hit too heavily within our ITU, and there were a lot of preparations made in the first wave. We risk-stratified all our patients using very helpful things like the BAUS [British Association of Urological Surgeons] guidelines, and we did stop a lot of our cancer activity in the first wave. But, having said that, we weren’t hit anywhere near as badly as we thought we might be. So, actually, all our preparations to some extent weren’t necessary, which was a lovely situation to be in. All of our TURBTs have carried on as normal. TURPs did stop for quite a while, but we restarted them about nine months ago, and since then we haven’t stopped.

And from a surgical point of view, you’re getting through them nice and quickly as well, it sounds. Other surgeons we’ve spoken to are awaiting the inevitable increase in muscle-invasive disease caused by a lack of activity during the pandemic. What are your thoughts on that?

I think it is a significant worry. The haematuria referrals do seem to have dropped. And so the concern is that there are a lot of people sitting out there with bad disease who have yet to present. I don’t think we’ve hit that at the moment – there’s not been a sudden increase in our cystectomy rate that I’m aware of. But we are certainly aware, anecdotally, of a number of late presentations because of COVID, because people didn’t want to present to their GP or felt they couldn’t at the time.

When Intuitive made the great leap forward of bringing in robotic surgery, the robots were going to be for cranial neurosurgery, reconstructive hand surgery – and they’ve ended up with the urologists. Urology used to be seen as a solid, workaday specialty, but now you guys are the rock stars. You have all the new toys to use. How on earth does that happen?

You just have to look at the patient who’s having open cystectomy on the ward afterwards versus the patient who’s had a robotic cystectomy. It’s an absolute game-changer. A completely different patient. I think everyone’s seen that. It’s becoming more and more common in urology – for cystectomy, certainly in our unit, and for prostatectomy and kidney surgery as well.

How many cystectomies do you do a year in Bristol?

Around 100 – we’re one of the busiest oncology centres in Europe for cystectomies and prostatectomies.

At what stage do you send your patients for radical cystectomy?

That’s a slightly two-pronged question in some respects. We actually talk to our patients about a radical cystectomy quite early – at the diagnosis step with our very high-risk patients, who would be fit for a cystectomy. So even probably before we’ve done their restaging TURBT, we would be mentioning the option of a primary cystectomy, because we know the outcomes are so much better if they have it with NMIBC versus if they progress to muscle-invasive disease and then have a cystectomy.

However, that isn’t the end of the story. A lot of patients won’t choose a primary cystectomy at that point. And I think if you were offered a number of different choices, you wouldn’t have it as your primary choice, either. So then the second point we’d be talking to them about a cystectomy would be if they’ve failed intravesical therapies, either BCG or HIVEC , dependent on what we’ve used for their particular situation.

Back in October at PROSCA in Ghent, we had patient advocates presenting a very interesting and sometimes emotional session on their experience. One of the speakers who’d had radical cystectomy is an old colleague and director of training for Boston Scientific’s urology division. He understands the roadmap, he’s had a Mitrofanoff, and he is very happy with it.

Yes, we’ve got a hugely eloquent patient group who’ve had cystectomies and are so supportive to patients coming up. One of our nurses, Helen Chilcott, helped set up our patient support group, and they’re an absolutely excellent bunch. They offer a buddy system for any patients just wanting to talk about cystectomy with someone who’s been through the experience and they’ve also produced patient information videos. They’re all so proactive. There’s nothing they can’t do having had a cystectomy – skydiving, horse riding, swimming, travelling. It’s an impressive group.

But let’s go back a page. We don’t want you to do any cystectomies. There are a lot of new drugs coming in, with the FDA extremely keen to license anything with a 30% recurrence-free survival rate at six months for BCG failure or BCG-refractory disease. What do you think is going to work – nadofaragene, pembrolizumab, valrubicin? Or are you just going to keep operating because you just like to operate?

I thought you were doing very well to pronounce some of those.

All down to practice!

[Laughs] There are so many different options now to think about and try to pronounce – they never make any simple names for them, do they! I think we may end up heading in that direction, using immunotherapy for non-muscle invasive bladder cancer. I think in the high-risk patients – certainly the ones that have failed intravesical therapy and aren’t fit for cystectomy – it’s potentially a good option for the future.

The concern is that the side-effect profile is still pretty high-risk for something that is non-muscle invasive. And because most of the patients we’re looking at currently are elderly and not fit for cystectomy, this means that their performance status isn’t great. Giving them medication that can have relatively toxic side effects would be quite concerning for some of them. So currently, the answer is we’re not involved in any of the trials, although we’re massively interested in what’s happening in them.

Do I think these drugs will come into the fray at some point? Yes, definitely. I guess my other concern is that whenever we put medication as an option and offer it to patients versus a cystectomy, when we know the drugs are potentially oncologically inferior, the patients may still choose the drug over losing their bladder. If patients were fit for a cystectomy and still wanted to go down one of the immunotherapy routes, we would have to carefully counsel them. At present, the recurrence-based survival rate certainly doesn’t compare to cystectomy.

So you have a patient come in with high-risk disease, you give them BCG, they recur at six months. You do a reTURBT, you give them a full one-year dose of BCG and immediate post-operative chemo and they come back with a recurrence of high-grade non-muscle invasive disease. What do you do?

At that point, if they weren’t fit for cystectomy, they would be offered HIVEC in Bristol. We’re very happy with the Combat HIVEC® system. But if the patient is fit for cystectomy, that is obviously the oncologically superior treatment for them. If for whatever reason they can’t have or don’t want a cystectomy and would prefer bladder preservation, and we do have a lot of patients that really just can’t stand the thought of it, then HIVEC is certainly a very good option for them, offering them a very good chance of recurrence-free long-term survival. So that would be our choice.

We occasionally do offer reinduction BCG, although if they failed at the six-month mark, you probably wouldn’t be talking to them about that. If it’s slightly longer out, you may think about a further course. But BCG does have a much higher side-effect profile and can affect quality of life more than HIVEC, so we’re quite honest with the patients about that. In fact, we are finding some BCG-naive patients wanting to have HIVEC over BCG, purely based on the side-effect profiles.

BCG has a much higher side-effect profile and can affect quality of life more than HIVEC, so we’re quite honest with patients about that. In fact, we’re finding BCG-naive patients wanting to have HIVEC over BCG, purely based on side-effect profiles.

Twenty-five years ago, bladder cancer treatment was BCG, mitomycin or nothing. We’ve moved on a bit today, with better TURBTs, better visualisation, better adherence to things like immediate post-operative dose and better understanding of stratification of the drug. We’ve parked the DeLorean in Southmead Hospital’s car park and paid the £300 parking charge – if you jumped in it and moved 25 years into the future, what would it look like?

I very much hope we’ll have found a cure with a tablet by then so we don’t have to do any surgery – we can all give up and retire. [Laughs] In truth, I think urinary biomarkers are probably going to play a much larger role, and not necessarily 25 years down the line, either. I’d say that in the next five years they’re going to be much more prevalent in the NHS for diagnosis and surveillance of bladder cancer.

I also think the use of MRI to stage bladder cancer will probably be much more standard. And it may be that we don’t end up doing a TURBT as a diagnostic test but just as a treatment. I don’t think there will be nanobots operating inside the bladder just yet, but give it a little bit longer than 25 years and who knows? I suspect we’re still going to be diagnosing with scopes and treating with scopes – I don’t think we’ll come up with anything to completely replace them for a long time yet. I think en-bloc will probably take over as the method of removal – the main technological issue stopping that at the moment is a retrieval bag for the specimen.

In every bladder meeting we’ve ever been in, we’ve asked, “Who here gives postoperative chemotherapy?” About half the hands go up. You said right at the start that you do it. Now that’s not innovative – that’s just adherence to guidelines. But half of people don’t do it. So is it important? And if it is, why don’t they give it?

I think it’s massively important and the evidence coming out is that it’s actually more important for the intermediate and the lower-risk groups than the high-risk groups. The main burden of bladder cancer is really the recurrence, with extended follow-up and surveillance. If you can reduce the number of times people need operations and flexible cystoscopy surveillance by giving one post-op chemo, then I have to say I genuinely can’t understand why people aren’t giving it. It might be that some people still struggle logistically to do that in theatre, though it seems relatively simple and straightforward.

We’ve already offered you a trip into the future. So benevolent are we with imaginary gifts that we’ve got another one for you. Boris Johnson loves the Bristol Urological Institute so much that today he’s giving you a £25 billion research grant. What are you going to spend it on tomorrow?

Hmm... £25 billion... it’s a large amount. I truly think that biomarkers are the way forward in terms of trying to reduce bladder-cancer surveillance. I think I would throw my money – if we’re having lots of it – at a number of different biomarkers that look promising, and see if we can get a better surveillance schedule.

With a view to a greater understanding of the disease or to be able to specifically tailor treatments?

I think both, really. If we could pick up the people that weren’t going to respond to BCG, for example, or those who weren’t going to respond to chemotherapy before cystectomy, if we could drill down into the genetics of the bladder cancer before we started the treatment and we knew that the treatment was going to work, that would be absolutely amazing. They’re already making a start with the PDL-1 inhibitors, aren’t they? So it is coming.

Go back 25 years, and a woman working as a consultant urologist would have been seen as a great innovation. How has that changed over your career so far?

There are several hundred of us around now, which is absolutely lovely. We even have a Women in Urology WhatsApp group, very ably supported by BAUS vice-president Jo Cresswell and Tamsin Greenwell, so we’re all connected, which is even better. One of the first consultants I ever worked for in urology didn’t think women should do any surgery. So that was a challenging job! Luckily, my other consultant at the time, Seamus MacDermott down in Torbay, was excellent – a brilliant mentor who luckily did believe women should be in surgery and who was one of the main reasons I wanted to do urology.

Obviously, views have changed over the years and people have accepted that women are excellent surgeons, equally competent as men. There are a lot more of us now – for trainees coming through in the southwest, I believe the females now outnumber the males.

BAUS have an excellent agenda for increasing diversity, and certainly the BAUS Oncology annual meeting I chaired on December 9 is a very diverse group. I think BAUS are moving in a really good direction.

Thank you very much for joining us. It’s fascinating to hear from a busy, innovative uro-oncological centre what’s being done now and what you expect to be doing in the next five, 10 and 25 years.

If you’re a fellow medical innovator and would like to share your views and ideas in this series, please email Guy Cooper at grc@combat-medical.com