En Bloc Resection vs. Standard Resection for Bladder Tumors: Multicenter Trial Results and Clinical Considerations - Jeremy Teoh
May 11, 2023
Jeremy Teoh joins Wei Shen Tan in a discussion on a multicenter randomized control trial comparing en bloc resection to standard resection for bladder tumors less than three centimeters in size. The primary outcome was the one-year recurrence rate, and secondary outcomes included progression rate and detrusor muscle sampling. The study focused on non-muscle invasive bladder cancer and recruited 276 patients after excluding benign and muscle-invasive cases. The results showed a statistically significantly lower one-year recurrence rate in the en-bloc resection group than in conventional resection. The one-year progression rate did not reach statistical significance. The study suggests that en bloc resection may be beneficial for reducing recurrence in low to intermediate-risk bladder cancers. The choice of energy modality (laser vs. bipolar) was a surgeon's preference, and the approach and adherence to oncological principles were emphasized as important factors in achieving better outcomes.
Biographies:
Jeremy Teoh, MBBS, FRCSEd (Urol), FCSHK, FHKAM (Surgery), Urologic Oncology Fellow at MD Anderson Cancer Center, Houston TX
Wei Shen Tan, MD, PhD, FRCS (Urol), Urologic Oncology Fellow, Department of Urology, MD Anderson Cancer Center, University of Texas, Houston, TX
Biographies:
Jeremy Teoh, MBBS, FRCSEd (Urol), FCSHK, FHKAM (Surgery), Urologic Oncology Fellow at MD Anderson Cancer Center, Houston TX
Wei Shen Tan, MD, PhD, FRCS (Urol), Urologic Oncology Fellow, Department of Urology, MD Anderson Cancer Center, University of Texas, Houston, TX
Read the Full Video Transcript
Wei Shen Tan: Good afternoon. I'm Shen Tan, a Urological Oncology Fellow at MD Anderson Cancer Center. Today I have here with me Professor Jeremy Teoh, who's an Associate Professor at Chinese University of Hong Kong. I've known Jeremy for a while and it's a pleasure to see you again, Jeremy.
Today we'll be discussing a paper that you'll be presenting at AUA, titled, "En Bloc Resection Versus Standard Resection for Bladder Tumor, A Multicenter Randomized Control Trial." Congrats, Jeremy, for completing this trial. As we know, it's always difficult to complete surgical trials. Can you brief us a little bit about the trial and what the outcomes are?
Jeremy Teoh: Yeah, sure. Good to see you, Shen. Really a pleasure. It is multicenter randomized trial, basically focusing on bladder tumors less than three centimeters in size. We try to randomize them to receive either en bloc resection or conventional TURBT.
The primary outcome is one-year recurrence rate. And we'll also look into some secondary outcomes, including one-year progression rate, detrusor muscle sampling, et cetera. Basically this study focused on non-muscle invasive bladder cancer. So it is a pre-plant analysis focusing on this group of patients only. So we recruited 350 patients, but then at the end of a study a number of patients have benign and also muscle invasive blood cancer. So after excluding these patients we have 276 patients. And then basically what we found is that the one-year recurrence rate was 38.1% in the conventional arm, versus 28.5% in the en bloc resection arm.
And it was statistically significant. For the one-year progression rate, it was 2.6% in the conventional arm versus 0% in the en bloc resection arm. But then this didn't reach a statistical significance, whereas for the other secondary outcomes including the detrusor muscle sampling rate, they were basically similar between the two arms. And for the same profile, again, they're quite similar between the two arms. So what we conclude from this study is that in patients with non-muscle invasive bladder cancer, less than three centimeter in size, en bloc resection did result in a lower recurrence rate of one year. When compared to the conventional TURBT.
Wei Shen Tan: It looks like a positive signal and it's actually one of the previous trials looking at en bloc did not show recurrence benefit. Comparing the previous randomized trial versus your trial, is there any reasons on why you could explain the differences in results?
Jeremy Teoh: Well I think the main reason is firstly the sample size compared to previous trials. I think our sample size is relatively larger. This is also the only trial that really use one year recurrence rate as you primarily come to calculate sample size. And secondly, I think it really depends on the quality of TURBT across the different centers in the trial. If you are doing a really good TURBT at your express center with very experienced surgeon, obviously the benefit of en bloc recession may not be that big.
But in a multi-center setting, in terms of the generous ability of the procedure, I think we did manage to show a benefit simply because en bloc resection, the way you do it, it's not merely just removal of the tumor in one piece, per se. It's basically a much more systematic way of really determining the margin circumferentially really getting into the muscle layer from the circumferential, normal detrusor muscle layer, and then gradually move towards the center. So you kind of get it into a correct [inaudible 00:04:00], in a much more systematic way. So I believe in this study the recurrence is really defined by histology. So I'm quite convinced that the results are really reflecting the genuine benefit of procedure.
Wei Shen Tan: Appreciating it's a randomized study, but were the cohorts well-balanced, meaning, did they both grade and stage wise, and also use of adjuvant intra cycle treatment between the two cohorts?
Jeremy Teoh: Yeah, basically the age tumor grading. We also look into the EAU risk groups. They are quite balanced between the two groups. In terms of the postoperative mitomycin C insulation, they are also similar between the two groups. Even for the rate of secondary resection and also BCG instillation. They're also similar between two groups. So at least it appears to be quite balanced. Yeah.
Wei Shen Tan: It's good to know. And also in your mind, which are the best group of patients that you would treat en bloc? Would you treat everyone, or would you tailor your approach based on the appearance of the tumor?
Jeremy Teoh: Well, this is more of my own opinion. So en bloc resection, there are two main benefits when compared to standard resection. Firstly is, when you do it in the en bloc manner then the margins are much more well-defined. It's not really judged by the surgeon's eyes alone, but instead you can look into margin histologically, whether it's a clear margin. And secondly, when you resect the tumor in one piece, you hope to reduce the amount of flowing tumor cells, reduce chance of seeding, et cetera. So this is more on a surgical side.
So if you can have a good local complete resection together with minimizing the risk of re-implantation, basically you can hopefully reduce the early disease recurrence.
But for really high grade diseases, really bad diseases, or patients with CIS, field change cancerization, then it's not only about surgery, you might need a lot more adjuvant treatment, BCG treatment, or even novel treatments, which may lead, hopefully, to a better control in long run as well.
So although this trial showed that it has a good benefit in reducing recurrence rate, in my opinion it's probably better for low grades or low risk or intermediate risk cancers. Whereas in high risk cancers, we probably need a combination of a good surgery together with a good adjunct treatment in order to have a good control. So that's what I believe.
Wei Shen Tan: And in terms of modality or treatment, laser versus endoscopic bipolar, or monopolar, do you have a preference? And what are your thoughts in terms of your breakdown? Were they quite similar? Does it matter? Does it not matter? What do you think?
Jeremy Teoh: In this particular study, we basically use bipolar for both the en bloc resection and also the conventional TURBT arm. From a personal perspective, I think using laser is particularly good for lateral wall tumors because there's no obturator reflex. It might be more difficult in bladder dome tumors because usually laser is end-firing and it's quite pointing towards the dome, and it's really quite difficult to ensure good depth resection. Even using bipolar can be difficult, but laser will be more difficult in my opinion.
And for bipolar, of course, you encounter any difficulty, then you can just switch back to conventional TURBT in a much more efficient manner. I think the approach is much more important. The approach of en bloc resection is primary, and what energy modality used really, in my opinion, is a surgeon preference most of the time. So to me it doesn't really matter.
Wei Shen Tan: So congrats again, Jeremy on your trial. Before we conclude, is there any final words that you would want to summarize the results of the key findings for our listeners?
Jeremy Teoh: Yeah, so in our study, basically we show that en bloc resection leads to a better cancer control in terms of one year recurrence rate. I think the key message that I want to deliver is that number one en bloc, this name, removal in one piece, sounds very sexy in a way. But I think the key point is that we should respect it as a cancer surgery. We should always do this procedure in a systematic way. We should try to preserve oncological principles as much as we can and sometimes we can't. We just confer back to the confession where that's also fine. But it's not only about the surgical approach, but also our mindsets of respecting it as a cancer surgery. And only when we do it in a very meticulous way, a systematic way every time, then hopefully we can achieve a better outcome in the long run.
Wei Shen Tan: Great. Thanks very much Jeremy.
Jeremy Teoh: Thank you. Thank you.
Wei Shen Tan: Good afternoon. I'm Shen Tan, a Urological Oncology Fellow at MD Anderson Cancer Center. Today I have here with me Professor Jeremy Teoh, who's an Associate Professor at Chinese University of Hong Kong. I've known Jeremy for a while and it's a pleasure to see you again, Jeremy.
Today we'll be discussing a paper that you'll be presenting at AUA, titled, "En Bloc Resection Versus Standard Resection for Bladder Tumor, A Multicenter Randomized Control Trial." Congrats, Jeremy, for completing this trial. As we know, it's always difficult to complete surgical trials. Can you brief us a little bit about the trial and what the outcomes are?
Jeremy Teoh: Yeah, sure. Good to see you, Shen. Really a pleasure. It is multicenter randomized trial, basically focusing on bladder tumors less than three centimeters in size. We try to randomize them to receive either en bloc resection or conventional TURBT.
The primary outcome is one-year recurrence rate. And we'll also look into some secondary outcomes, including one-year progression rate, detrusor muscle sampling, et cetera. Basically this study focused on non-muscle invasive bladder cancer. So it is a pre-plant analysis focusing on this group of patients only. So we recruited 350 patients, but then at the end of a study a number of patients have benign and also muscle invasive blood cancer. So after excluding these patients we have 276 patients. And then basically what we found is that the one-year recurrence rate was 38.1% in the conventional arm, versus 28.5% in the en bloc resection arm.
And it was statistically significant. For the one-year progression rate, it was 2.6% in the conventional arm versus 0% in the en bloc resection arm. But then this didn't reach a statistical significance, whereas for the other secondary outcomes including the detrusor muscle sampling rate, they were basically similar between the two arms. And for the same profile, again, they're quite similar between the two arms. So what we conclude from this study is that in patients with non-muscle invasive bladder cancer, less than three centimeter in size, en bloc resection did result in a lower recurrence rate of one year. When compared to the conventional TURBT.
Wei Shen Tan: It looks like a positive signal and it's actually one of the previous trials looking at en bloc did not show recurrence benefit. Comparing the previous randomized trial versus your trial, is there any reasons on why you could explain the differences in results?
Jeremy Teoh: Well I think the main reason is firstly the sample size compared to previous trials. I think our sample size is relatively larger. This is also the only trial that really use one year recurrence rate as you primarily come to calculate sample size. And secondly, I think it really depends on the quality of TURBT across the different centers in the trial. If you are doing a really good TURBT at your express center with very experienced surgeon, obviously the benefit of en bloc recession may not be that big.
But in a multi-center setting, in terms of the generous ability of the procedure, I think we did manage to show a benefit simply because en bloc resection, the way you do it, it's not merely just removal of the tumor in one piece, per se. It's basically a much more systematic way of really determining the margin circumferentially really getting into the muscle layer from the circumferential, normal detrusor muscle layer, and then gradually move towards the center. So you kind of get it into a correct [inaudible 00:04:00], in a much more systematic way. So I believe in this study the recurrence is really defined by histology. So I'm quite convinced that the results are really reflecting the genuine benefit of procedure.
Wei Shen Tan: Appreciating it's a randomized study, but were the cohorts well-balanced, meaning, did they both grade and stage wise, and also use of adjuvant intra cycle treatment between the two cohorts?
Jeremy Teoh: Yeah, basically the age tumor grading. We also look into the EAU risk groups. They are quite balanced between the two groups. In terms of the postoperative mitomycin C insulation, they are also similar between the two groups. Even for the rate of secondary resection and also BCG instillation. They're also similar between two groups. So at least it appears to be quite balanced. Yeah.
Wei Shen Tan: It's good to know. And also in your mind, which are the best group of patients that you would treat en bloc? Would you treat everyone, or would you tailor your approach based on the appearance of the tumor?
Jeremy Teoh: Well, this is more of my own opinion. So en bloc resection, there are two main benefits when compared to standard resection. Firstly is, when you do it in the en bloc manner then the margins are much more well-defined. It's not really judged by the surgeon's eyes alone, but instead you can look into margin histologically, whether it's a clear margin. And secondly, when you resect the tumor in one piece, you hope to reduce the amount of flowing tumor cells, reduce chance of seeding, et cetera. So this is more on a surgical side.
So if you can have a good local complete resection together with minimizing the risk of re-implantation, basically you can hopefully reduce the early disease recurrence.
But for really high grade diseases, really bad diseases, or patients with CIS, field change cancerization, then it's not only about surgery, you might need a lot more adjuvant treatment, BCG treatment, or even novel treatments, which may lead, hopefully, to a better control in long run as well.
So although this trial showed that it has a good benefit in reducing recurrence rate, in my opinion it's probably better for low grades or low risk or intermediate risk cancers. Whereas in high risk cancers, we probably need a combination of a good surgery together with a good adjunct treatment in order to have a good control. So that's what I believe.
Wei Shen Tan: And in terms of modality or treatment, laser versus endoscopic bipolar, or monopolar, do you have a preference? And what are your thoughts in terms of your breakdown? Were they quite similar? Does it matter? Does it not matter? What do you think?
Jeremy Teoh: In this particular study, we basically use bipolar for both the en bloc resection and also the conventional TURBT arm. From a personal perspective, I think using laser is particularly good for lateral wall tumors because there's no obturator reflex. It might be more difficult in bladder dome tumors because usually laser is end-firing and it's quite pointing towards the dome, and it's really quite difficult to ensure good depth resection. Even using bipolar can be difficult, but laser will be more difficult in my opinion.
And for bipolar, of course, you encounter any difficulty, then you can just switch back to conventional TURBT in a much more efficient manner. I think the approach is much more important. The approach of en bloc resection is primary, and what energy modality used really, in my opinion, is a surgeon preference most of the time. So to me it doesn't really matter.
Wei Shen Tan: So congrats again, Jeremy on your trial. Before we conclude, is there any final words that you would want to summarize the results of the key findings for our listeners?
Jeremy Teoh: Yeah, so in our study, basically we show that en bloc resection leads to a better cancer control in terms of one year recurrence rate. I think the key message that I want to deliver is that number one en bloc, this name, removal in one piece, sounds very sexy in a way. But I think the key point is that we should respect it as a cancer surgery. We should always do this procedure in a systematic way. We should try to preserve oncological principles as much as we can and sometimes we can't. We just confer back to the confession where that's also fine. But it's not only about the surgical approach, but also our mindsets of respecting it as a cancer surgery. And only when we do it in a very meticulous way, a systematic way every time, then hopefully we can achieve a better outcome in the long run.
Wei Shen Tan: Great. Thanks very much Jeremy.
Jeremy Teoh: Thank you. Thank you.