Ashish Kamat: Welcome to UroToday's Bladder Cancer Center of Excellence. My name is Ashish Kamat I'm Professor of Urology and Cancer Research at MD Anderson Cancer Center in Houston. We're fortunate today to be joined by three colleagues from the UK today. Dr. Veeru Kasivisvanathan who is a clinical lecturer of urology and current professor at the University College of London. Dr. Kevin Gallagher, who's a urology specialist registrar, and a clinical research fellow at the Western General Hospital in the UK, and Dr. Nikita Bhatt who's a urology specialist registrar east of England, UK. Welcome, everyone.

Veeru Kasivisvanathan: Hi!

Nikita Bhatt: Thank you.

Ashish Kamat: We're actually going to be hearing from two of our guests today, and then we'll have an open discussion with all three of them on a very interesting study that caught our attention called the RESECT study. Kevin, I understand you're going to start and lead the show. So it's all yours.

Kevin Gallagher: Thank you, professor Kamat and UroToday for giving us the opportunity to talk about our new study, RESECT. RESECT is a global prospective observational study about TURBT surgery. The study is run by BURST, the British Urology Researchers in Surgical Training. We are a UK-based, but global research collaborative. The objective of the study is to improve the quality of TURBT surgery and thus improve outcomes in nonmuscle-invasive bladder cancer. We know that doing a good TURBT particularly giving into the cycle of chemotherapy significantly improves outcomes in patients, but there's evidence that we just don't do it. This study suggested only 50% of centers in the US were routinely giving single shots of mitomycin C and only about 6% of the time. From a study in Scotland, where I work, we know that what we are proposing with the RESECT study works. This work led by [inaudible] in Scotland and a member of the RESECT steering group showed that there was evidence of huge variation in the achievement of TURBT quality across Scotland's health boards.

They started measuring this and publishing it in a report every year and, low and behold, the quality of TURBT surgery rapidly increased. And, there's emerging evidence that that is making a difference to outcomes. We have the opportunity, you have the opportunity and to do this with us across the world and in your hospital to rapidly improve outcomes for patients undergoing TURBT surgery.

RESECT aims to be the largest study of TURBT ever performed. We will collect anonymous data about patients undergoing TURBT, we'll collect data about the surgery, and also about things that may impact the achievement of TURBT's quality and TURBT surgery in different hospitals, across different surgeons. The primary outcome of this study is the proportion of TURBT surgeries achieving the quality indicators. Key quality indicators will include amongst others, the resection of the detrusor muscle, the administration of single-shot interphase cycle chemotherapy within 24 hours, and the performance of re-TURBT in relevant cases. The secondary outcome is the early recurrence rate. I'm going to hand over to Dr. Bhatt, now, who's going to tell you how easy it is to get involved in a study and to begin to make a difference for your patients.

Nikita Bhatt: Thanks, Dr. Gallagher. So this is no ordinary study. This study will open recruit thousands of patients and report on them leading to direct patient benefit within two years. We're looking for sites to take part now and register within the next six months, aiming to publish in early 2023. So how can you get involved? We've currently opened up preregistration for sites, which you can do using the link here. We will approach interested individuals to apply for national coordinators soon, similar to our previous BURST projects, this can be approved as it gets notes reviewed or an audit in most centers. You will then receive a database login to enter data anonymously from your center. As a part of the project, surgeons can also look at their performance live as the project goes on.

Finally, why get involved? Well, looking at previous BURST projects like MIMIC and IDENTIFY a study with 11,000 patients with hematuria, this will be the largest TURBT study ever performed. The returns will be fast. It's very straightforward to take part, register, and enter data with a minimum requirement of ethics. You will have the opportunity to present the project at various meetings, take part in manuscript writing depending on the level of your contribution, and then publish your national and local data, as well. But ultimately, this is aimed at improving our TURBT practice internationally, but the live feedback during the study will give you the opportunity to improve your own practice as you go along. So please take part in this global study on TURBT by registering on the link here, www.bursturology.com/resect. Thank you.

Ashish Kamat: That was great. And thank you so much for that very concise introduction to our audience. A couple of questions. If I might open it up to all three of you and feel free to take this in no particular order, but one of the questions that I have is what exactly are you looking to study and identify in this other than observational TURBT data points? What's the hypothesis here?

Kevin Gallagher: The primary outcome is to determine what the achievement of quality is and the range of that across the world. That's an observation outcome and as a primary outcome, but it's an important one because, and to have the drive to improve, we're going to need to know where we sit on that scale of achieving these indicators. We don't actually know how good hospitals are across the world at achieving quality in TURBT. That's the primary outcome and the first thing. But in terms of making a difference, and what's the hypothesis of the study that you asked there, a key hypothesis is that by measuring and reporting the achievement of these quality indicators, back to surgeons and hospitals, we can actually make a difference. We can actually make an improvement in the practice of the surgery and in one of the short term outcomes, which is the early recurrence rate.

Veeru Kasivisvanathan: And it's Dr. Veeru Kasivisvanathan, Chair of the BURST Research Collaborative. I might add one point to the points Kevin made. And part of our design involves collecting a proportion of data from their TURBT practice retrospectively. We then report some of the results from those two centers, and we then prospectively collect some of the data on their TURBT quality. So there'll be a way of us directly assessing the impact of what we're doing in this on TURBT outcomes.

Ashish Kamat: Okay. And that's a good point because that's one of the questions I was going to ask you is, are you going to marry this with a little bit of retrospective identification and study as to what's ongoing in centers already? You know, in our center, for example, we do about 1,500 TURBTs a year, and we do have our own inbuilt quality control systems. Are you going to factor that into your study? Are you going to allow different centers to build in their own quality control metrics, or is it something that most centers will have to be agnostic regarding their own quality control?

Veeru Kasivisvanathan: So in terms of using our data collection system, we use REDCap, which is an international trial level-approved database. And the idea would be that the data points we collect have been decided on by our internal and external peer review process. And so in order to generalize outcomes across different centers, we will have to stick by the data points we've set out to collect. However, if centers also use their own inbuilt system, there's no reason why they can't be entered on both of them. One of the things we try to do in our piloting process of the data collection sheet is to make sure it's as user friendly as possible. So we'll go through several phases of development. And one of those will be to make sure that data collection is not too onerous to make sure that the use of the system is straightforward and unambiguous.

So that was our current plan.

Kevin Gallagher: I could add a little bit there, Veeru, to reduce workload potentially in centers that may have their own data collection processes. There is a facility in REDCap to bulk upload data. If some of the data is collected in exactly the same way or with a little bit of modification and can be directly uploaded to REDCap rather than having to be entered on a per-patient basis.

Ashish Kamat: Okay, great. Let me just ask each one of you to comment a little bit on what kind of optical enhancement to regular TURBT is used at your centers. This is a little bit off-topic from the specific question of the registry, but I'll get to another question as a followup. So if you want to start, Kevin?

Kevin Gallagher: So for an all new TURBTs at our hospital, so for first tumor resections, we use blue light PDD for all new tumors and have done for some years.

Ashish Kamat: And do you also use blue light in follow-up in office cystoscopies?

Kevin Gallagher: No, we don't. It's just for the first rigid cystoscopy resections.

Ashish Kamat: Okay, Nikita?

Nikita Bhatt: So I work in a relatively small hospital at the moment, and we, unfortunately, don't have any optical enhancements either for diagnosis or recurrence.

Ashish Kamat: What about narrow-band imaging? Do you have that access to that capability?

Nikita Bhatt: No, it's got just the flexible cystoscopy. 

Ashish Kamat: Okay, Veeru?

Veeru Kasivisvanathan: Yeah, so we don't use narrow-band imaging, but I work in a London teaching hospital center. We do use PPP blue light cystoscopy in certain circumstances. I think Kevin's center for the UK is probably an exception rather than the standard. His center is quite well advanced due to some of the PIs in his center. I think we tend to use it in specific indications or in patients in whom there is a persistent suspicion of bladder cancer, or for example, CIS, they might have a positive cytology in whom we haven't seen anything or in those who have an existing tumor and we're looking for some concurrent CIS.

Ashish Kamat: Okay. So, obviously, there's a lot of push globally to provide our patients with "the best possible TURBT" and one of the quality metrics that has been proposed by several guidelines in agencies is the use of optical enhanced cystoscopy, regardless of whether it's a PDD or NBI, or if you have OCT or any other technology. Is that something that has been accounted for in the RESECT study? And if so, what the [inaudible] variation, even amongst the three of you on the panel, how will that be statistically analyzed?

Kevin Gallagher: So it's one of the data points that we will collect about the TURBTs and whether there has been optical enhancement used. It's not going to be one of the stipulated quality indicators in the study currently from our discussions that we've had in the steering committee. The primary outcome is the achievement of the quality indicators. We don't plan to account for the use of optical enhancements statistically, but it will be reported. So, we will be assessing factors which cause higher achievement of TURBT quality and the use of optical enhancement will be assessed as one of those potential factors leading to higher achievement, or for instance, complete resection or resection of the detrusor muscle.

Veeru Kasivisvanathan: So what are the ways in which we can look at this in our secondary outcomes? As Kevin said, is looking at the factors that predict achievement of quality indicators or a secondary outcome, three-month recurrence rates. And so what you do is you use the imaging assistant used as one of the variables of interest, and it may be narrow-band imaging, blue light cystoscopy, or neither. And that would be one of the variables in the multi-variant regression. You can do some formal statistical analysis on it to see whether the odds ratio for using one of those imaging systems is significantly associated with achieving quality indicators or recurrence rate at three months.

Ashish Kamat: Okay. To clarify, your primary endpoints are whether there's presence or absence of the detrusor muscle in the specimen, whether the patient got perioperative chemotherapy and whether a re-TURBT was performed. And I presume that's for high-grade disease. Correct?

Kevin Gallagher: So, where indicated. So if it was, for instance, an incomplete resection or, there was no detrusor muscle in the specimen for tumors higher than G1Ta. So where indicated.

Ashish Kamat: Okay, great. And then the secondary endpoint is early recurrence rate as defined at what time point?

Nikita Bhatt: First follow-up. So re-TURBT or first check cystoscopy.

Ashish Kamat: So three months. And so when we enter a patient in the study, does that mean that the follow-up is the first follow-up essentially, and after that, the patient drops off the study?

Nikita Bhatt: Currently, that's what we have planned, but BURST has always been quite responsive to its collaborators. So, if we think there's interest and if this first phase of the study is a success, then we can plan to continue follow-up and possibly continue it for a year to show outcomes at one year as well.

Ashish Kamat: Okay, great. Again, I commend the three of you for putting together this very important initiative. As you may or may not know I've been a big proponent of improved quality of TURBT for many, many years. It is one of those surgeries that we tend to not recognize as probably the most critical part of the management of bladder cancer patients. Because if you don't do a good TURBT, everything subsequently can pretty much go down the wrong path, either under staging or just plain wrong treatment. I really commend the three of you. In closing, I want to give you the floor again. So just closing thoughts from each one of you.

Veeru Kasivisvanathan: Thank you very much, Professor Kamat and UroToday, for giving us the opportunity to talk about our study. We really do feel that, as you've pointed out, this is an area which can improve patient outcomes. We think by getting involved in this study, you can do that for your patients and globally, from the data we obtain, we'll be able to produce something quite meaningful in a short time period. And we hope to, as we've demonstrated in our previous studies, for example, identify looking at the diagnosis of bladder cancer. We can produce quite large studies quite quickly. So please do get involved.

Nikita Bhatt: Yeah, thanks. Thank you very much for inviting us to interview today. I think for me, the single biggest thing on why I would take part in such a study is to see where we stand. So it's going to give you an opportunity to see how you're performing in your center or personally, compared to the world. As we've already mentioned that this is one operation that directly reflects a patient outcome. So this is quite important and I'd urge you all to please register and help us out in getting great patient numbers.

Kevin Gallagher: Yes. So thank you very much for the opportunity to speak today. Our previous studies are a testament to the fact that this is going to be a great study. And what I think is great about TURBT is that every urologist should be trained to do this surgery, but the variation in how it's done is huge. As a urology trainee, you're still training in how to do the surgery. I know that I haven't properly reviewed how well I'm doing it, looked at all my cases, and saw how many I'm resecting the detrusor muscle in. And this study is going to provide a really nice way to see exactly how you are performing against your peers and thus how you might improve.

Ashish Kamat: Great. So once again, thank you so much for taking the time, stay safe, and stay well.

Kevin Gallagher: Thank you very much.

Nikita Bhatt: Thank you, thank you very much.