CUT-less Trial Aims to Eliminate Secondary TURBT in Non-Muscle Invasive Bladder Cancer - Francesco Del Giudice
May 5, 2025
Ashish Kamat interviews Francesco Del Giudice about the CUT-less trial, which aims to streamline the treatment pathway for non-muscle invasive bladder cancer. Dr. Del Giudice explains that despite being the most common urological procedure for cancer, TURBT remains a "neglected procedure" where patients often require a second resection due to uncertainty about the quality of the first. The CUT-less trial combines pre-operative MRI using the VI-RADS scoring system with intraoperative PDD (photodynamic diagnosis) to potentially eliminate the need for repeat TURBT in select patients. The non-inferiority trial will randomize 370 patients between standard care (white light TURBT followed by repeat TURBT) and the experimental arm (single PDD-TURBT with no repeat procedure). With primary outcomes focused on three-month recurrence rates, the study aims to demonstrate that this approach is oncologically safe while reducing patient burden and healthcare costs.
Biographies:
Francesco Del Giudice, PhD, FEBU, Assistant Professor of Urology, Department of Maternal Infant and Urologic Sciences, Sapienza University of Rome, Rome, Italy
Ashish Kamat, MD, MBBS, Professor of Urology and Wayne B. Duddleston Professor of Cancer Research, University of Texas, MD Anderson Cancer Center, Houston, TX
Biographies:
Francesco Del Giudice, PhD, FEBU, Assistant Professor of Urology, Department of Maternal Infant and Urologic Sciences, Sapienza University of Rome, Rome, Italy
Ashish Kamat, MD, MBBS, Professor of Urology and Wayne B. Duddleston Professor of Cancer Research, University of Texas, MD Anderson Cancer Center, Houston, TX
Read the Full Video Transcript
Ashish Kamat: A warm welcome to all of you from the UroToday studios. I'm Ashish Kamat, Professor of Urologic Oncology at MD Anderson Cancer Center in Houston, Texas, and we're live at AUA 2025, in Vegas. Welcoming to our studio is Francesco, who has come to us all the way from Italy, and he's going to be talking to us about the CUT-less trial. So welcome, Francesco.
Francesco Del Giudice: That is correct. And thank you very much for the kind words, the invitation, and once again to UroToday for being here today and discussing about our important trial. That is, for sure, important for us and hopefully for the community, especially in our UA system, where most of the national health systems are provided, and where there is probably really a need for a partnership in terms of management of bladder cancer.
So why CUT-less trial? So when we started looking at the algorithm, according to our European Association of Urology guidelines, we have always been thinking about that nowadays with all the multi-disciplinary and translational research that we have from pre-operative imaging into intraoperative tools like PDD or MBA, we will really need to do something to potentially cut out the arduous path that this patient has.
And when we talk about non-muscle-invasive bladder patients, one of your-- my preferred definition of this procedure, the TURBT, is that for urology is a neglected procedure. I was a student, when I was a resident, when I was looking at this tutorial, and I truly share that opinion. It's a neglected procedure, but at the same time is the most prevalent, more utilized, more commonly used over the training period procedure that we do for cancer, for non-muscle-invasive bladder cancer, which is for sure the 80%, and the vast majority, of all of this disease.
When I moved towards-- currently I'm doing a fellowship in cystectomies in London. And I will be coming back in Rome at the end of the year, and I will eventually start my practice in bladder cancer. I always find it very difficult to discuss to a patient about that after his primary resection, he will need to undergo a secondary TURBT, just because we are unaware or unsure about the quality of the primary resection itself.
And it is really difficult to explain to someone that just undergo the same exact procedure that has to be done because, after almost 60 years of TURBTs, we are still not sure about the diagnostic, the complete resection, and finally the complete eradication of the primary non-muscle-invasive bladder cancer disease.
So with that, we decided that especially in our center in Rome, in Sapienza University of Rome, where our radiology center is very important. Professor Valeria Panebianco has developed the VI-RADS score system for pre-operative detection of non-muscle versus muscle-invasive bladder cancer. So we try to combine the pre-operative advantages of MRI pathway that would give you the certainty of identifying pre-TURBT, those patients that are really non-muscle-invasive bladder cancer, and trying to implement an intraoperative tool-- like PDD and Photocure that is going to be the main sponsor of our trial-- in order to potentially redefine the criteria for those who could skip a secondary resection, always in a safe environment, I would say.
Ashish Kamat: So explain to us a little bit about the typical patient that comes in. And when you're counseling the patient-- pretend I'm the patient. Explain the trial to me.
Francesco Del Giudice: Yeah. So what we will do is that we will just put in front of the patient what is the current algorithm. We will explain that given his pre-operative characteristics, it's very likely that he might be a high risk or intermediate high-risk non-muscle-invasive bladder cancer. And if this will be confirmed after the primary resection, we will need to do a second resection.
In the trial, we will just submit every patient to a pre-operative MRI in order to have the idea of the extension of the disease before the resection itself. To have a VI-RADS score that should be only VI-RADS score 1 and 2, which is our pre-enrollment criteria necessary to get into the randomization. And then the patient will be allocated to the current standard of care-- which would be primary white light TURBT, followed by a secondary white light TURBT in about two to six weeks time-- versus our experimental arm, which is actually removing a procedure from the pathway.
So the patient will just undergo their primary PDD-TURBT, and then we'll just follow it up according to our EAU guidelines schedule. So they will have BCG, they will have induction. And then the primary outcome will be looking at the recurrence rate at three months after the primary resection.
So we wanted specifically to have an outcome that could be a surrogate of the quality of the resection rather than looking in the long or mid-term outcomes of survival where we know, especially, for example, from the PHOTO trial, that the survival disadvantages of the adoption of one PDD or now would eventually potentially disappear.
So this is going to be the trial-- is actually quite easy in the way that it's been designed. The experimental part would be, actually, the removal of their secondary TURBT in their experimental group. And then patients will be just followed in terms of oncological outcomes as normal schedule.
Ashish Kamat: So let me ask you a couple of questions. Because, again, there is data that suggests that if you use optical-enhanced technologies such as PDD, you are improving the quality of the resection. So my personal bias is that I think you will have a good positive trial. How does implementing the VI-RADS-- other than taking out the higher-risk patients-- but how does implementing the VI-RADS potentially help this in the future when you're trying to make it broadly applicable?
Francesco Del Giudice: So secondary TURBT, or re-TURBT, is recommended for two main recommendations. The first of all is understaging bladder cancer after the primary resection. So those patients who are T1 might potentially harboring a T2 disease, which is just not be sampled because of the quality issues, which are inherent in our primary resection.
And the other real issue for which EAU guidelines would recommend a secondary resection is that there are plenty of series describe that incomplete resections are up to possibly 70% of the series. So there are two main issues-- the understaging that should be covered by our pre-operative VI-RADS, which, by identifying only VI-RADS score 1 and 2 should very reliably only tell us after the primary resection that T1 patient is actually a real T1 patient, and we are not missing the risk of losing a T2.
And the intraoperative announcement of PDD will actually help us to improve taking down the persistent disease after the primary resection, so clearing the margin, identifying those CIS lesions that would otherwise be missed. So it's the combination of the two tools-- the VI-RADS and the intraoperative PDD that might go together-- giving you enough, I would say security safety to avoid safely a secondary resection because one is doing something that either could eventually not cover for. So that would be the rationale.
Ashish Kamat: Great, great. And, again, where are you as far as the whole trial? How many patients enrolled? Has it reached a certain point yet? And what's the power calculation?
Francesco Del Giudice: So thank you. So this is going to be a non-inferiority trial. So whenever we'll be able to demonstrate that the new pathway, basically, is not inferior to the standard of care, we would eventually be able to safely keep going. In order to do so, we will need to enroll, in the next three years, an amount of number that would be 370 patients that will be equally standardized in both arms, and that would eventually follow off for the rest of the period.
But what I think will be very, very nice from this trial is that our primary aim is actually a very short-term aim because we are worried about, once again, of the quality indicators from the resection that would be the early bladder cancer recurrences. So we will hopefully be able to have an interim analysis that will be arriving after one year of the trial that will start.
Unfortunately, as you know, dealing with interventional pharmaceutical trials is really painful, and sometimes the schedule is a little bit delayed, so we are planning to have our first patient enrolled by the beginning of October 2025, and hopefully we'll be finishing in time. But what I think will be much more striking, in terms of our EAU implications, is that whenever we will achieve oncological efficacy, so we will be able to demonstrate there is non-inferiority to trials.
The implication would be for the patients, in terms of health-related quality of life, so less hospitalization, less anesthesia, less complication potentially related to a non-trivial procedure like a re-TURBT. And even more strikingly would be the economical short and long-term analysis that we are planning. So we will hope that, of course, the direct hospital costs should be favoring our approach because we are effectively implementing more money in terms of MRI and PDD, for sure, but we are definitely avoiding a secondary procedure.
And also in the long run, if you think about bladder cancer is also indirect cost is all these kind of issues. The quality-adjusted life would be eventually very, very significant. And this could potentially, a little bit, redefine-- if you will be successful-- the current indication of EAU guidelines.
And last thing I want to tell you is that we are, right now, as a single-center trial. So we developed this idea in collaboration with our radiology department with Professor Panebianco and our radiology team. But if after one year of interim analysis, we were able to detect safety outcomes from the trial, what we would like to do is expand our boundaries and eventually include and become a multicentric by including the UK center-- where I am currently doing my fellowship nowadays-- and as well the US hopefully.
So hopefully we will hope to bring the CUT-less trial to an international multicentric level, which will be probably even more hard than painful, but I think that would be the level of evidence at that point that could give us a reliable and safe indication to potentially shift the current algorithm.
Ashish Kamat: Well, congratulations on getting this off the ground. Wishing you the best of luck, and hopefully we'll have you back here next year, at least to give us some preliminary results.
Francesco Del Giudice: I really hope for the interim analysis. We'll be here, and we'll be more than grateful. And I really want to thank you so much for the invitation once again.
Ashish Kamat: Thank you.
Francesco Del Giudice: Thank you very much.
Ashish Kamat: A warm welcome to all of you from the UroToday studios. I'm Ashish Kamat, Professor of Urologic Oncology at MD Anderson Cancer Center in Houston, Texas, and we're live at AUA 2025, in Vegas. Welcoming to our studio is Francesco, who has come to us all the way from Italy, and he's going to be talking to us about the CUT-less trial. So welcome, Francesco.
Francesco Del Giudice: That is correct. And thank you very much for the kind words, the invitation, and once again to UroToday for being here today and discussing about our important trial. That is, for sure, important for us and hopefully for the community, especially in our UA system, where most of the national health systems are provided, and where there is probably really a need for a partnership in terms of management of bladder cancer.
So why CUT-less trial? So when we started looking at the algorithm, according to our European Association of Urology guidelines, we have always been thinking about that nowadays with all the multi-disciplinary and translational research that we have from pre-operative imaging into intraoperative tools like PDD or MBA, we will really need to do something to potentially cut out the arduous path that this patient has.
And when we talk about non-muscle-invasive bladder patients, one of your-- my preferred definition of this procedure, the TURBT, is that for urology is a neglected procedure. I was a student, when I was a resident, when I was looking at this tutorial, and I truly share that opinion. It's a neglected procedure, but at the same time is the most prevalent, more utilized, more commonly used over the training period procedure that we do for cancer, for non-muscle-invasive bladder cancer, which is for sure the 80%, and the vast majority, of all of this disease.
When I moved towards-- currently I'm doing a fellowship in cystectomies in London. And I will be coming back in Rome at the end of the year, and I will eventually start my practice in bladder cancer. I always find it very difficult to discuss to a patient about that after his primary resection, he will need to undergo a secondary TURBT, just because we are unaware or unsure about the quality of the primary resection itself.
And it is really difficult to explain to someone that just undergo the same exact procedure that has to be done because, after almost 60 years of TURBTs, we are still not sure about the diagnostic, the complete resection, and finally the complete eradication of the primary non-muscle-invasive bladder cancer disease.
So with that, we decided that especially in our center in Rome, in Sapienza University of Rome, where our radiology center is very important. Professor Valeria Panebianco has developed the VI-RADS score system for pre-operative detection of non-muscle versus muscle-invasive bladder cancer. So we try to combine the pre-operative advantages of MRI pathway that would give you the certainty of identifying pre-TURBT, those patients that are really non-muscle-invasive bladder cancer, and trying to implement an intraoperative tool-- like PDD and Photocure that is going to be the main sponsor of our trial-- in order to potentially redefine the criteria for those who could skip a secondary resection, always in a safe environment, I would say.
Ashish Kamat: So explain to us a little bit about the typical patient that comes in. And when you're counseling the patient-- pretend I'm the patient. Explain the trial to me.
Francesco Del Giudice: Yeah. So what we will do is that we will just put in front of the patient what is the current algorithm. We will explain that given his pre-operative characteristics, it's very likely that he might be a high risk or intermediate high-risk non-muscle-invasive bladder cancer. And if this will be confirmed after the primary resection, we will need to do a second resection.
In the trial, we will just submit every patient to a pre-operative MRI in order to have the idea of the extension of the disease before the resection itself. To have a VI-RADS score that should be only VI-RADS score 1 and 2, which is our pre-enrollment criteria necessary to get into the randomization. And then the patient will be allocated to the current standard of care-- which would be primary white light TURBT, followed by a secondary white light TURBT in about two to six weeks time-- versus our experimental arm, which is actually removing a procedure from the pathway.
So the patient will just undergo their primary PDD-TURBT, and then we'll just follow it up according to our EAU guidelines schedule. So they will have BCG, they will have induction. And then the primary outcome will be looking at the recurrence rate at three months after the primary resection.
So we wanted specifically to have an outcome that could be a surrogate of the quality of the resection rather than looking in the long or mid-term outcomes of survival where we know, especially, for example, from the PHOTO trial, that the survival disadvantages of the adoption of one PDD or now would eventually potentially disappear.
So this is going to be the trial-- is actually quite easy in the way that it's been designed. The experimental part would be, actually, the removal of their secondary TURBT in their experimental group. And then patients will be just followed in terms of oncological outcomes as normal schedule.
Ashish Kamat: So let me ask you a couple of questions. Because, again, there is data that suggests that if you use optical-enhanced technologies such as PDD, you are improving the quality of the resection. So my personal bias is that I think you will have a good positive trial. How does implementing the VI-RADS-- other than taking out the higher-risk patients-- but how does implementing the VI-RADS potentially help this in the future when you're trying to make it broadly applicable?
Francesco Del Giudice: So secondary TURBT, or re-TURBT, is recommended for two main recommendations. The first of all is understaging bladder cancer after the primary resection. So those patients who are T1 might potentially harboring a T2 disease, which is just not be sampled because of the quality issues, which are inherent in our primary resection.
And the other real issue for which EAU guidelines would recommend a secondary resection is that there are plenty of series describe that incomplete resections are up to possibly 70% of the series. So there are two main issues-- the understaging that should be covered by our pre-operative VI-RADS, which, by identifying only VI-RADS score 1 and 2 should very reliably only tell us after the primary resection that T1 patient is actually a real T1 patient, and we are not missing the risk of losing a T2.
And the intraoperative announcement of PDD will actually help us to improve taking down the persistent disease after the primary resection, so clearing the margin, identifying those CIS lesions that would otherwise be missed. So it's the combination of the two tools-- the VI-RADS and the intraoperative PDD that might go together-- giving you enough, I would say security safety to avoid safely a secondary resection because one is doing something that either could eventually not cover for. So that would be the rationale.
Ashish Kamat: Great, great. And, again, where are you as far as the whole trial? How many patients enrolled? Has it reached a certain point yet? And what's the power calculation?
Francesco Del Giudice: So thank you. So this is going to be a non-inferiority trial. So whenever we'll be able to demonstrate that the new pathway, basically, is not inferior to the standard of care, we would eventually be able to safely keep going. In order to do so, we will need to enroll, in the next three years, an amount of number that would be 370 patients that will be equally standardized in both arms, and that would eventually follow off for the rest of the period.
But what I think will be very, very nice from this trial is that our primary aim is actually a very short-term aim because we are worried about, once again, of the quality indicators from the resection that would be the early bladder cancer recurrences. So we will hopefully be able to have an interim analysis that will be arriving after one year of the trial that will start.
Unfortunately, as you know, dealing with interventional pharmaceutical trials is really painful, and sometimes the schedule is a little bit delayed, so we are planning to have our first patient enrolled by the beginning of October 2025, and hopefully we'll be finishing in time. But what I think will be much more striking, in terms of our EAU implications, is that whenever we will achieve oncological efficacy, so we will be able to demonstrate there is non-inferiority to trials.
The implication would be for the patients, in terms of health-related quality of life, so less hospitalization, less anesthesia, less complication potentially related to a non-trivial procedure like a re-TURBT. And even more strikingly would be the economical short and long-term analysis that we are planning. So we will hope that, of course, the direct hospital costs should be favoring our approach because we are effectively implementing more money in terms of MRI and PDD, for sure, but we are definitely avoiding a secondary procedure.
And also in the long run, if you think about bladder cancer is also indirect cost is all these kind of issues. The quality-adjusted life would be eventually very, very significant. And this could potentially, a little bit, redefine-- if you will be successful-- the current indication of EAU guidelines.
And last thing I want to tell you is that we are, right now, as a single-center trial. So we developed this idea in collaboration with our radiology department with Professor Panebianco and our radiology team. But if after one year of interim analysis, we were able to detect safety outcomes from the trial, what we would like to do is expand our boundaries and eventually include and become a multicentric by including the UK center-- where I am currently doing my fellowship nowadays-- and as well the US hopefully.
So hopefully we will hope to bring the CUT-less trial to an international multicentric level, which will be probably even more hard than painful, but I think that would be the level of evidence at that point that could give us a reliable and safe indication to potentially shift the current algorithm.
Ashish Kamat: Well, congratulations on getting this off the ground. Wishing you the best of luck, and hopefully we'll have you back here next year, at least to give us some preliminary results.
Francesco Del Giudice: I really hope for the interim analysis. We'll be here, and we'll be more than grateful. And I really want to thank you so much for the invitation once again.
Ashish Kamat: Thank you.
Francesco Del Giudice: Thank you very much.