Episode 41: In the Clinic - Discussing bladder radiotherapy and preservation in Bladder cancer with Professor Ananya Choudhury

Join us for this episode focusing on the role of radiotherapy in the treatment of bladder cancer. We talk to leading bladder radiotherapy expert Professor Ananya Choudhury.

Ananya is passionate about all things bladder cancer related and discusses her views on bladder preservation and radiotherapy.

She makes a strong case for bladder radiotherapy in muscle invasive bladder cancer versus surgery and we review the evidence.

We also talk about the use of 'plan of the day' and on set imaging in radiotherapy.

This is a fascinating insight from a world expert in bladder cancer.

We hope you enjoy.

Transcript

Simply Oncology Podcast Recording_ Bladder preservation-20250114_132945-Meeting Recording

January 14, 2025, 1:29PM

Hello, I'm doctor John Mc Grane and I'm doctor Michael Rowe. And in this episode, we are going to be looking at muscle invasive bladder cancer and specifically looking at the role of radiotherapy and to do that we have.
 Delighted to invite Professor Ananya Choudhury from the Christie Hospital in Manchester on the show today and then you're welcome.

 CHOUDHURY, Ananya (THE CHRISTIE NHS FOUNDATION TRUST)   0:47
 Hello, lovely to see you both.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   0:50
 Alright. And Anya, I don't think we could have a stronger voice in the room when it comes to muscle invasive bladder cancer. When we think about treatment with radiotherapy or bladder preservation for muscle invasive bladder cancer. But could you set the scene there might be some people listening who might not be fully engaged with the muscle veins of bladder cancer. You know what kind of options are when we when we've got that.
 You know, muscle invasive, bladder cancer and MDT.
CHOUDHURY, Ananya (THE CHRISTIE NHS FOUNDATION TRUST)   1:22
 In this case, we're talking about localised muscle invasive bladder cancers, so people who have the cancer solely within the bladder and it hasn't spread outside.
 As with many solid tumours, there is data suggesting that patients can be treated with surgery, but they can also be treated with non-surgical modalities and often that means that you can.
 Actually, conserve the organ. We see it in prostate cancer head and neck, oesophageal, pancreas. You know, cervix, you know lots and lots of solid tumours. And we also see this in bladder cancer. So, in muscle invasive bladder cancer that hasn't spread.
 Patients can have treatment either with surgery as the main component of their radical treatment, or with radiotherapy as the main component. And yet what's really interesting is if you look at the data out there.
 The vast majority of patients, certainly outside the UK and in some centres in the UK, get treated with surgery. But when you discuss the treatment options with patients and you're doing sort of public patient information gathering or doing surveys, a lot of patients will say that they never realised that they could have had an alternative treatment to surgery, so.
 Within the bladder cancer community, we have a we have we have I think quite an quite an important disconnect.
 Between what we think the options are for patients and maybe this is because we're all non-surgical oncologists, right?
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   3:06
 Mm hmm.
CHOUDHURY, Ananya (THE CHRISTIE NHS FOUNDATION TRUST)   3:06
 And what the perception of treatment is out there, both with patients and their families, but actually also I think with a lot of our surgical colleagues as well, there is there is there's a lot of data that shows that the outcomes with surgery and radiotherapy.
 Are the same.
 Especially once you take into account.
 Known prognostic factors, so if you take into account how old the patient is, whether they have comorbidities or not, you know how advanced the cancer is, using the TNM staging.
 You actually find that the survival curves with surgery and radiotherapy are slap bang on top of each other and we've actually known this for decades. This isn't new information. There are studies dating back to the 70s and 80s that showed that show this.
 But because to date, there's never been a prospective trial directly comparing surgery with radiotherapy.
 Lots of people seem to dismiss the Stata, and the difficulty is that certainly in the UK there will never be a prospective trial.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   4:22
 And there will be people sitting, listening, thinking how lazy is bladder cancer as a community. But it's not that we haven't tried this. We have tried to have surgery versus radiotherapy, but that trial just didn't complete Recruitment, isn't that right?
CHOUDHURY, Ananya (THE CHRISTIE NHS FOUNDATION TRUST)   4:36
 Absolutely. So I think in the UK to be absolutely fair to us, we identified the gap in knowledge and we tried to do this trial and actually we tried to do this trial, you know almost 20 years ago and what we found was that over the course of three years.
 We couldn't recruit patients, patients into this study and the team that did the study, they did a lot of work looking at why that you know why that would be and what they found.
 And was that a lot of patients when they realised that we didn't know whether surgery or radiotherapy was better?
 But, and given the differences between the two treatments, you know, one is very big operation.
 Really potentially lots of side effects debilitating and you know really have a huge impact on, you know, on life versus a treatment that doesn't require a big operation.
 And actually has less of an impact on life.
 Patients didn't want to be randomised and you know that was that was actual true patient choice.
 So we couldn't recruit to it in three years. We recruited less than 50 patients and that means that quite rightly, we stopped trying to do that study and no other country as far as I'm aware has tried to do that study. So, at the moment we are in an evidence free zone and.
 We have to deal with the best data that we have, actually what's really interesting is that Brazil have actually just announced that they have, they are going to fund a study comparing surgery with radiotherapy. So, if they can recruit, then we might actually have an answer to this question within the next decade.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   6:32
 Now, really, just as you say, ties back to what you were saying, right, the beginning of the episode is that often that conversation about the equipoise between the two choices and the fact that there is more than one choice is sometimes not being had. And then suddenly when you put it in a clinical trial scenario, when it has to be had, then patients usually have a very, very clear idea as to what they want out of treatment.
CHOUDHURY, Ananya (THE CHRISTIE NHS FOUNDATION TRUST)   6:55
 Absolutely sorry, John.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   6:55
 Well, I think you know we see patients coming through a urological diagnostic pathway and they see the surgeons and then of course.
 You know the amount of times that people come to my clinic saying, well, of course surgery's the gold standard and you're like, well, it's only that's been established through practise but not through evidence. I want to ask.
CHOUDHURY, Ananya (THE CHRISTIE NHS FOUNDATION TRUST)   7:16
 But somebody's decided, right? Somebody's decided the girls under the surgery.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   7:18
 Yep. I want to ask you a question. You must have been asked a million times, and I knew.
 So we've got this equipoise between surgery and radiotherapy, who is a good surgical candidate in your book and who is a radiotherapy candidate.
CHOUDHURY, Ananya (THE CHRISTIE NHS FOUNDATION TRUST)   7:42
 Because I think are important. If you're trying to identify people who will benefit from surgery rather than radiotherapy.
 Are to do with symptoms. So if we have a patient who has a lot of symptoms from their bladder cancer or have a lot of urinary symptoms regardless of their bladder cancer, then I think as non-surgeons we have to be very honest.
 Our radiotherapy is not going to make that better.
 Hopefully we won't make it worse and there's quite a lot of data saying that the long term side effects from bladder radiotherapy are actually really quite low, but we're not going to make it better. So if I have a patient in clinic and you say you know, what's your priority, you know what's the most important thing you want out of this treatment apart from curing your bladder cancer and they say I want to stop getting up 12 * a night.
 Then actually surgery is going to be the best treatment for them, providing their fit enough to have surgery. The only other group of patients that I.
 Would steer away from radiotherapy are patients who've previously had radiotherapy in their pelvis because potentially with those patients you do put them at additional risk of side effects in the future. Having said that.
 Of course, I have treated patients who've had previous pelvic radiotherapy and especially if the radiotherapy has been a long time ago, they do pretty well. So, I don't think it's a deal breaker, but I think those are the sort of things that I'd consider.
 Who's suitable for radiotherapy? Pretty much everyone.
 And I, you know, they're all the patients who aren't suitable for surgery, are suitable for radiotherapy.
 Are there patients who are particularly suited for radiotherapy? Well, those are the patients that are, I think the surgeons would want as well. So anybody who's fit who is engaged and committed because they will have to have quite a lot of follow up after they've had their radiotherapy.
 You know, patients who have small tumours who don't have a lot of comorbidities, they are all ideal candidates for radiotherapy, but they're ideal candidates for surgery as well.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   10:05
 Now we keep on talking about radiotherapy, but it's not just radiotherapy alone that we're talking about here. It's radiotherapy with a radiosensitizer and that's where a lot of the evidence is in terms of better outcomes.
 There's a number of radio sensitizers that you can choose. Obviously the two, the two main ones are chemotherapy or carbogen & nicotinamide, what factors do you consider when so first of all you'd I assume you would want to use a radio sensitizer in everyone having radical radiotherapy.
CHOUDHURY, Ananya (THE CHRISTIE NHS FOUNDATION TRUST)   10:34
 Absolutely user agent sensitizer to everyone.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   10:37
 And what factors do you consider when you're choosing the type of radiosensitizer do you choose? Do you prefer one or the other? Does it kind of depend on what your centre has?
CHOUDHURY, Ananya (THE CHRISTIE NHS FOUNDATION TRUST)   10:47
 I think that's a really interesting question. There are a number of radio sensitizers available, but there's I suppose there's four that are used commonly. There's gemcitabine, there's mitomycin C and 5 FU. There's cisplatin and there's carbogen & nicotinamide.

Other drugs have been used for radio sensitisation like taxane, but they tend to not be used as widely and.
 
 So there's two things we don't know. We don't know if any radios sensitizer is better than any other radios sensitizer. And we also don't know whether certain patients benefit from 1 radiosensitiser rather than another. And the reality is that we're never going to do the clinical trial to compare the radiosensitizers. You'd have to design it as a non-inferiority if you're comparing all four radiosensitizers, that's thousands of patients.
 And it's just never going to happen. It's unrealistic to think that it would. So, I think we have to deal with the data that we have.
 Often the data that we have, as far as we can tell is that all the radio sensitizers are pretty much as good as each other. So the important thing is to give a radio sensitizer and choosing the best radio sensitizer is down to what is available in your practise, what is acceptable to the patient and you know what's easy to deliver.
 And I'm always a big fan of cost effectiveness as well. So, we should be considering that there is biomarker work to try and see whether we can select the right radiation.
 For patients, but we're not at the point where any of those biomarkers are ready for the clinic. So I think that's still an ongoing research.
 Project.
 Personally, I tend to use two radio sensitizers I either use carbogen & nicotinamide, or I use low dose gemcitabine but I don't have a good robust way of selecting a radio sensitizer for the patient in front of me.

 ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   13:01
 But I think that's a really good point. You've got one chemo sensitizer, and your team learns how to use that and to use it consistently and use it well. And then you have that backup with the carbogen and nicotinamide for somebody that may fall just underneath that chemotherapy radiosensitiser. And that's certainly what we do. But we're a mitomycin and 5 FU team in terms of chemo.
 But we've carbogen and nicotinamide for those patients that we feel might be better suited to that.
 
 
CHOUDHURY, Ananya (THE CHRISTIE NHS FOUNDATION TRUST)   13:31
 I think you're absolutely right, John. Basically, it means that I haven't used radiotherapy alone.
 For years, I can't remember the last time I gave a patient radiotherapy alone because, like you said, there's always. There's always something I can give, even if it's just the carbogen without the nicotinamide. But I think that also raises the point about radiotherapy alone. There's a lot of people who will say you should never give radiotherapy alone. And I've heard people stand up at meetings and say that I don't think that's right.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   13:47
 Yeah, yeah.
CHOUDHURY, Ananya (THE CHRISTIE NHS FOUNDATION TRUST)   14:02
 And I think radiotherapy alone is actually an option that's better than either not treating the patient or treating the patient palliatively if you can get in a radical dose of radiotherapy. So, I don't think we should assume that there is no place for radiotherapy alone. There might be a select patient for whom who can tolerate 4 weeks of radiotherapy, but who for whatever reason.
 Will not tolerate a radiosensitiser.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   14:31
 Now in bladder cancer, there's been a lot happening. Now we're going to try and stay within the kind of muscle and vas of radiotherapy sphere and we're not going to get drawn into too much of Tom Powell's.
 Although there are a lot of exciting ones of those, Rader trial reported recently and that was a kind of de-escalation and trial. Do you want to talk us through the results of that?
CHOUDHURY, Ananya (THE CHRISTIE NHS FOUNDATION TRUST)   14:58
 Rada was auk. Well actually it was an international trial because not only did we recruit patients in the UK as a bladder community.
 The US, The Australians and Kiwis recruited patients as well, and it was a randomised phase two trial. There were three groups within the trial. The first group was standard of care.
 Whatever that standard of care is pretty much.
 And I think that's important because I think that did impact on the results of the study.
 The second group was plan of the day.
 Where each patient had three plans generated as opposed to the one that most patients have a small a medium and a large plan and on a daily basis, the radiographers did their pre-treatment imaging and then decided which plan was going to be used.
 Whether it was a small, medium or large, depending on the bladder volume on that day and then the third group looked at plan of the day. But alongside that did a concomitant boost to the tumour bed.
 And DS de-escalated the dose to the rest of the bladder.
 And what is interesting, I think about the trial is that like many clinical trials, it is it can be interpreted depending I think on what your belief system is of a clinician. So, if you're a believer, you.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   16:39
 None.
CHOUDHURY, Ananya (THE CHRISTIE NHS FOUNDATION TRUST)   16:42
 Support the positives of the trial or you believe in the positives of the trial. If you're sitting on the fence or you're nonbeliever, I don't think the results of the trial push you in a direction to believe it's a positive trial. Officially it's a negative trial, right? The Raiders primary objective was to look at toxicity at two years with the hypothesis that the.
 Plan of the day or and the OR the de-escalation of dose to the most of the bladder would reduce.
 Toxicity at two years and there was no significant difference between the three groups.
 So actually what Raiders said so the first thing I think Raider says to me is the outcomes are really good. Seriously, people look at the paper, look to see what contemporary management of muscle invasive, bladder cancer with non-surgical treatment gives you the patient, the outcomes of a good week, your bladder cancer.
 Without patients having to have, you know, debilitating operations. So that's my first take home message. OK, you can tell me that the other trials are decades old, but this is this is modern treatment that we're giving. I think the second message that I give when I'm describing RAIDER is that you can do this treatment without having fancy technology and get good outcomes anywhere in the world that has radiotherapy machines you can give this treatment, it doesn't have to have to be.
 Daily image guided, although it doesn't have to be on an MR Linac, it doesn't have to have plan of the day. It doesn't have to have fancy, you know, resource intensive treatment going on. You get good outcomes with pretty basic treatment that is standard right across the world.
 And going back to the cost effectiveness thing, I think that's a really important message.
 My concern has always been with daily image guided radiotherapy and then reducing the margins as I've always worried about there being pelvic recurrence.
 Either BCOM BC 2001 were really interesting studies because the pelvic nodal recurrence was really low, despite us not treating the pelvic nodes in Rader, we haven't treated the pelvic nodes and the pelvic recurrence is 7%.
 That's really low. You know, every time the surgeons turn round to us and go. Oh, but we take all the lymph nodes out and you don't do anything to the lymph nodes. We have really good data now to say maybe you don't need to take all those lymph nodes out because look, because look, when you give new adjuvant chemo or maybe it's because you give new adjuvant chemo.
 So maybe it's because we're giving incidental dose of lymph nodes. We don't have a huge problem with pelvic nodal recurrence, isolated pelvic nodal recurrence. When we do bladder preservation with radiotherapy. So, I think that's a really good.
 Outcome from the trial as well.
 And then finally, I think what it tells us is that.
 We can do.
 Fancy radiotherapy across multiple centres within a you know a country like the UK. So, within this sort of healthcare systems that we have, if there is a need to do fancy radiotherapy, if there are patients who we think would benefit from doing having plan of the day. If there were patients where for some reason maybe they've had previous pelvic radiotherapy. So you want to try and reduce the dose a little bit to the pelvis.
 This by de-escalating some of the bladder, then actually we can do that, we can do it in all sorts of centres, big, small, you know, loads of resources, fewer resources and the patients get a good outcome from it.
 I think what's going to be difficult about the radar study is for the believers, for everybody who's truly believes that we should be doing plan of the day or dose de-escalating.
 We don't the evidence for that, it's going to be hard to Commission something like that or to encourage people outside the bladder community is that's what we should be doing and we're not going to do this trial again. So for everybody who thinks, oh, well, if only we'd had more numbers because it's underpowered or maybe we should have asked fewer questions or, well, it's because we now do image guided radiotherapy standard and that's where the biggest gain was.
 Is actually knowing that we're treating the target and not treating, not treating too much bowel on a daily basis.
 Yeah, that might be true. But we're not doing the trial again. So again, we have to use the best data that we have, and we have to interpret it in the best way that we can.

And Anya, thank you so much. There was a fantastic we've gone through a huge amount in terms of muscle invasive bladder cancer, radiotherapy surgery, future directions, particularly in terms of novel therapies and also straight into you know some of the, the political and the and the ethical.
 Basis for those therapies. Now we're going to finish up this episode and I'm going to ask you what rather than three take away points, I'm going to ask you what your three. If you have 3 wishes.
 To improve outcomes in bladder cancer generally.
 What would those be?

 CHOUDHURY, Ananya (THE CHRISTIE NHS FOUNDATION TRUST)   42:00
 So I think having more advocacy and more information out there and more awareness of bladder cancer and its diagnosis for the patients, but also the treatment options and outcomes that those treatment options give.
 I would like more resources for my for the bladder cancer service. I think in a lot of practises bladder cancer plays.
 The forgotten about younger sibling to prostate cancer. I think prostate cancer, there are many more, many more men with prostate cancer. I think often all of us are distracted by what's going on in the prostate cancer world and we have to be reminded that you know that our bladder cancer patients deserve.
 The best treatment and all the support that we can give them as well.
 And.
 So to associate with that, I think having more research resources so you know, so blood, you know, bladder cancer actually is a rare cancer. We see it ends up not being considered a rare cancer because we group together non-muscle invasive bladder cancer and muscle invasive bladder cancer into numbers. If you take muscle invasive bladder cancer as a disease by itself it is actually qualifies as a rare cancer but it doesn't it doesn't.
 Those resources, and we it would be good to have money to do research that is focused on our bladder cancer patients, whether that is you know improving techniques and technology, finding out more about the biology or actually finding meaningful biomarkers that will help us select the right treatments for Patients in clinic.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   44:00
 I want you to know, and I knew that we did give some people Christmas wishes, but nobody has ever been allowed three wishes.
 And that is it. And that is kind of as thanks for being so honest with your views, so forthright and clearly a massive believer in radiotherapy and bladder preservation as am I.
 So thank you so much for that.
CHOUDHURY, Ananya (THE CHRISTIE NHS FOUNDATION TRUST)   44:27
 Thank you. Thank you so much for inviting me to come and talk to you both today.
ROWE, Michael (ROYAL CORNWALL HOSPITALS NHS TRUST)   44:32
 Thanks very much.