Risk Stratification for Active Surveillance in Low and Intermediate-Risk Bladder Cancer - Marco Moschini
April 1, 2025
Ashish Kamat speaks with Marco Moschini about expanding active surveillance criteria for recurrent low-grade bladder cancer. Dr. Moschini presents his single-center retrospective study from San Raffaele Hospital analyzing outcomes among intermediate-risk non-muscle invasive bladder cancer patients based on IBCG risk stratification. These findings demonstrate that patients with zero risk factors achieve 86% recurrence-free survival and 92% high-grade recurrence-free survival at three years, while those with one to two risk factors show comparable protection from high-grade recurrence (94%). Only patients with three or more risk factors had substantially higher risk of high-grade recurrence (24% at three years). The researchers conclude that active surveillance might safely be expanded to include select intermediate-risk patients, particularly those with zero to two risk factors. Dr. Moschini emphasizes the importance of accurate pathology and patient compliance with follow-up when implementing active surveillance protocols, noting that treatment decisions ultimately require personalized, patient-centered approaches rather than rigid algorithms.
Biographies:
Marco Moschini, MD, PhD, Urologist, Department of Urology, San Raffaele Hospital, Università Vita e Salute San Raffaele University, Milan, 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:
Marco Moschini, MD, PhD, Urologist, Department of Urology, San Raffaele Hospital, Università Vita e Salute San Raffaele University, Milan, 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: Hello, everyone. And welcome to UroToday's Bladder Cancer Center of Excellence. I'm Ashish Kamat, Professor of urologic oncology at MD Anderson Cancer Center. And joining us today on the stage is Professor Marco Moschini, who's been with us before talking about multiple things in bladder cancer. And today, Marco, it's a pleasure to welcome you and learn what you have to share with us about your recent publication, which I think was very timely because there's more of a recognition nowadays that patients with low-grade recurrent bladder cancer can sometimes avoid repeated procedures and go on active surveillance. But we all want to figure out is there the best way to identify the optimal candidate. And that's the title of your presentation. So take it away.
Marco Moschini: Thank you for the kind invitation. Very happy to be here to present our work. So I would like to start with a very small introduction, saying that actually active surveillance with all the other treatments and therapies that we offer for de-escalation is gaining a lot of new publications and new data, new exciting data to allow our patients to receive better and more tailored treatment.
And in this case, I reported here what actually say the EAU guidelines, the AUA, and NCCN, suggesting that actually for low-risk, low-grade patients might be a good idea to offer active surveillance. But in our paper, we try to expand a little bit to this concept. So we use, of course, IBCG classification, sub stratification and said, OK, should we try also to give some to our intermediate risk patients this opportunity to active surveillance instead of an active treatment. And especially, we tried. And I will show you the data to analyze how good perform the patient with zero risk factor in the intermediate risk group IBCG classification and patient with one to two risk factors.
So our data were actually a single-center, retrospective analysis from data from San Raffaele Hospital in Milan, Italy. We had all the patients treated with transurethral resection and with complete follow-up. We included in our analysis all patients who could fulfill potentially the criteria for active surveillance. All the patients have less than five suspicious lesions, no active macro hematuria. The patient, of course, was treated with TURBT. There was a negative urine cytology collected before the surgery, and the major lesion, the index lesion, was smaller than one centimeter.
Then I will show you the Kaplan-Meier analysis. On the left side, there is the recurrence-free survival analysis stratified according to the three subgroups for intermediate risk group and the IBCG classification. And you can see for the overall recurrence rate, it performed actually very well. So the patient with the zero risk factor at three years had 86% recurrence-free survival. For a patient with one to two risk factors, 76%. And the patients who actually have three or more risk factors had a recurrence rate of 54%.
On the right side, we also analyzed the risk of having high-grade recurrence. And in this case, you can see that having zero risk factor or one to two risk factors perform actually almost the same. So the recurrence-free rate was 92% at three years for the zero risk groups and 94% for the patient having one to two risk factors. On the other hand, having three or more risk factors was associated with a higher risk of having high-grade recurrence at three years, with 76%.
So our summary was actually that we could support very good the prognosis of patients with intermediate risk non-muscle invasive bladder cancer for the subgroup having zero risk factor, but also for the subgroup having one to two risk factors, suggesting that these patients are very low risk of harboring a high-grade recurrence during the follow-up. On the other hand, the subgroup with three or more risk factors were associated with an increased risk of developing high-grade recurrence. And so should probably be spared for these active surveillance protocols. So thank you very much for your attention.
Ashish Kamat: Thank you so much, Marco. And thank you for doing this work. When we first proposed the IBCG risk classification back in 2014, it was based on expert consensus. And then it was modified in 2022, again, based on some existing data because Dr. Soloway and others had published on active surveillance. But clearly, we require work, such as what you've done, to show that you can use these criteria to fit patients into appropriate categories correctly. And active surveillance is something that's gaining more recognition and acceptance. But we have to make sure that we do patients no harm when we put them on active surveillance. So tell us a little bit. Are you using these criteria now in your clinic, in your practice to counsel patients? How are you using these criteria?
Marco Moschini: So now we just started our active surveillance protocol. Of course, when you start an active surveillance protocol, you want to start with the very best candidate. And you want to start with very low-risk patients, just because we personally do not have a lot of experience on active surveillance. And that's why the reason. And so at this moment, we are not treating the intermediate risk group patients with active surveillance. We started this paper with that idea, actually. We want to expand that because I do believe actually that there is a space also in the intermediate risk group of offering active surveillance. And that was the first step. So now knowing that with our data that actually patients with zero risk factor, one to two risk factors, perform really well, it's an impulse more for us to say, OK, we can also offer active surveillance to show the data to our patient, to say you are safe to be treated with active surveillance. There is no risk and no harm to choose this path.
Ashish Kamat: Right. Exactly. Because again, it's not for every patient. But there are some patients that are older, on anticoagulation, or just don't want to have a procedure. Or sometimes we feel, well, they've had too many procedures. So let's not keep traumatizing the bladder. And knowing the data that you have that shows, especially for the high grade, because that's what patients worry about, going from low-grade to high-grade and showing the minimal, extremely small risk of high-grade recurrence is very important.
So tell me a little bit about the study design. Because obviously, when you have patients that already have existing tumors and then you talk about high-grade recurrences, that's easy to understand. But help the audience understand what you meant by recurrence-free survival in patients that already have existing tumors.
Marco Moschini: Well, that is always difficult when you do analysis with non-muscle invasive bladder cancer because you have so many elements, and we have a huge database collecting prospectively all our patients, all our history. So it's difficult sometimes to differentiate an entity from an event, which is the huge problem and a huge dilemma when you try to do analysis on non-muscle invasive bladder cancer. But actually, we started from a definite set point. And we also included patients who had previously recurrence or previously tumors.
And so these patients were patients with a history of recurrent tumor within one year and so could fit in this sort of category. Because in my mind, the idea was if I start tomorrow in my practice to have an active surveillance protocol, I will see also patients having, for example, a recurrence yesterday. And I want to have a model where I'm able to put all these categories and to explain exactly to the patient his risk at three years of having high-grade recurrence, for example. So the patient can balance very well the chance of having it or to choose other types of treatments.
Ashish Kamat: Great. Now, that's a good point. And the other thing that's coming up recently is you have active surveillance, but then you also have office fulguration, you have chemo ablation, all other ways to de-intensify the treatment. And you've been part of the IBCG's most recent retreat, where we're talking about the ways to address intermediate risk. Share with our audience a little bit your thoughts on where you think office fulguration, chemo ablation, and active surveillance fit in. Not necessarily just for this paper, but in general, what is your thought process for those patients?
Marco Moschini: Well, I think there are several considerations that you need to make when you decide to do one treatment instead of the other, for example, cost, but also the idea of the patient of receiving a treatment or undergoing active surveillance. I would stress on two different points that for me are understudied. One is the ability of the pathologist to correctly diagnose the high-grade tumor or a variant histology, for example.
Because when I start an active surveillance protocol, I really want to have my pathologists giving a report that actually I have from the previous TURBT. Because what I see sometimes when I do a revision of the pathology is that in our series, at least, we had a 20% to 30% of change in the diagnosis because a local pathologist is probably more associated to skipping aberrant histology or skipping a high-grade tumor. And this is something that I don't want, at least for this type of treatment.
And the second part, the second important part that I think is always missing in this kind of discussion is also the willingness of the patients to come and do the follow-up and to do the treatment. And that is not just a follow-up for active surveillance, but also like, for example, doing the maintenance treatment after an induction. Or also for the chemo ablation, if you have a scheme of chemo ablation, that requires also a patient to come and to do the treatment properly, and all parameters that you have to keep in account.
Of course, the laser fulguration, if you have it, it's easier because you just use it, and then you just need to follow-up the patient. But from the other side, you feel more relief because in a way, you already give treatment. So you have to consider all these parameters. I'm trying to build a diagram in our hospital so for all the urologists who just follow the line and follow the diagram. But sometimes it's not so easy to capture all these elements in one diagram. And so sometimes it requires also a little bit of workup with the patient to understand needs and the actual problems.
Ashish Kamat: Of course. Now, I mean, those are great points. But I like what you said at the end because it truly is a patient-centric approach. And it's a shared decision-making between us and the patient. If you could put everything in an algorithm, then we could just have AI run your clinic. You don't need to have Professor Moschini in there with all your wisdom and nuances. So that's very important. It has to be personalized and tailored to each patient. And it's not a cookie cutter, just everybody fits one paradigm. Marco, I want to thank you always for your interest in expanding the field and for taking the time today. Thank you very much.
Marco Moschini: Thank you. Thank you for the invitation.
Ashish Kamat: Hello, everyone. And welcome to UroToday's Bladder Cancer Center of Excellence. I'm Ashish Kamat, Professor of urologic oncology at MD Anderson Cancer Center. And joining us today on the stage is Professor Marco Moschini, who's been with us before talking about multiple things in bladder cancer. And today, Marco, it's a pleasure to welcome you and learn what you have to share with us about your recent publication, which I think was very timely because there's more of a recognition nowadays that patients with low-grade recurrent bladder cancer can sometimes avoid repeated procedures and go on active surveillance. But we all want to figure out is there the best way to identify the optimal candidate. And that's the title of your presentation. So take it away.
Marco Moschini: Thank you for the kind invitation. Very happy to be here to present our work. So I would like to start with a very small introduction, saying that actually active surveillance with all the other treatments and therapies that we offer for de-escalation is gaining a lot of new publications and new data, new exciting data to allow our patients to receive better and more tailored treatment.
And in this case, I reported here what actually say the EAU guidelines, the AUA, and NCCN, suggesting that actually for low-risk, low-grade patients might be a good idea to offer active surveillance. But in our paper, we try to expand a little bit to this concept. So we use, of course, IBCG classification, sub stratification and said, OK, should we try also to give some to our intermediate risk patients this opportunity to active surveillance instead of an active treatment. And especially, we tried. And I will show you the data to analyze how good perform the patient with zero risk factor in the intermediate risk group IBCG classification and patient with one to two risk factors.
So our data were actually a single-center, retrospective analysis from data from San Raffaele Hospital in Milan, Italy. We had all the patients treated with transurethral resection and with complete follow-up. We included in our analysis all patients who could fulfill potentially the criteria for active surveillance. All the patients have less than five suspicious lesions, no active macro hematuria. The patient, of course, was treated with TURBT. There was a negative urine cytology collected before the surgery, and the major lesion, the index lesion, was smaller than one centimeter.
Then I will show you the Kaplan-Meier analysis. On the left side, there is the recurrence-free survival analysis stratified according to the three subgroups for intermediate risk group and the IBCG classification. And you can see for the overall recurrence rate, it performed actually very well. So the patient with the zero risk factor at three years had 86% recurrence-free survival. For a patient with one to two risk factors, 76%. And the patients who actually have three or more risk factors had a recurrence rate of 54%.
On the right side, we also analyzed the risk of having high-grade recurrence. And in this case, you can see that having zero risk factor or one to two risk factors perform actually almost the same. So the recurrence-free rate was 92% at three years for the zero risk groups and 94% for the patient having one to two risk factors. On the other hand, having three or more risk factors was associated with a higher risk of having high-grade recurrence at three years, with 76%.
So our summary was actually that we could support very good the prognosis of patients with intermediate risk non-muscle invasive bladder cancer for the subgroup having zero risk factor, but also for the subgroup having one to two risk factors, suggesting that these patients are very low risk of harboring a high-grade recurrence during the follow-up. On the other hand, the subgroup with three or more risk factors were associated with an increased risk of developing high-grade recurrence. And so should probably be spared for these active surveillance protocols. So thank you very much for your attention.
Ashish Kamat: Thank you so much, Marco. And thank you for doing this work. When we first proposed the IBCG risk classification back in 2014, it was based on expert consensus. And then it was modified in 2022, again, based on some existing data because Dr. Soloway and others had published on active surveillance. But clearly, we require work, such as what you've done, to show that you can use these criteria to fit patients into appropriate categories correctly. And active surveillance is something that's gaining more recognition and acceptance. But we have to make sure that we do patients no harm when we put them on active surveillance. So tell us a little bit. Are you using these criteria now in your clinic, in your practice to counsel patients? How are you using these criteria?
Marco Moschini: So now we just started our active surveillance protocol. Of course, when you start an active surveillance protocol, you want to start with the very best candidate. And you want to start with very low-risk patients, just because we personally do not have a lot of experience on active surveillance. And that's why the reason. And so at this moment, we are not treating the intermediate risk group patients with active surveillance. We started this paper with that idea, actually. We want to expand that because I do believe actually that there is a space also in the intermediate risk group of offering active surveillance. And that was the first step. So now knowing that with our data that actually patients with zero risk factor, one to two risk factors, perform really well, it's an impulse more for us to say, OK, we can also offer active surveillance to show the data to our patient, to say you are safe to be treated with active surveillance. There is no risk and no harm to choose this path.
Ashish Kamat: Right. Exactly. Because again, it's not for every patient. But there are some patients that are older, on anticoagulation, or just don't want to have a procedure. Or sometimes we feel, well, they've had too many procedures. So let's not keep traumatizing the bladder. And knowing the data that you have that shows, especially for the high grade, because that's what patients worry about, going from low-grade to high-grade and showing the minimal, extremely small risk of high-grade recurrence is very important.
So tell me a little bit about the study design. Because obviously, when you have patients that already have existing tumors and then you talk about high-grade recurrences, that's easy to understand. But help the audience understand what you meant by recurrence-free survival in patients that already have existing tumors.
Marco Moschini: Well, that is always difficult when you do analysis with non-muscle invasive bladder cancer because you have so many elements, and we have a huge database collecting prospectively all our patients, all our history. So it's difficult sometimes to differentiate an entity from an event, which is the huge problem and a huge dilemma when you try to do analysis on non-muscle invasive bladder cancer. But actually, we started from a definite set point. And we also included patients who had previously recurrence or previously tumors.
And so these patients were patients with a history of recurrent tumor within one year and so could fit in this sort of category. Because in my mind, the idea was if I start tomorrow in my practice to have an active surveillance protocol, I will see also patients having, for example, a recurrence yesterday. And I want to have a model where I'm able to put all these categories and to explain exactly to the patient his risk at three years of having high-grade recurrence, for example. So the patient can balance very well the chance of having it or to choose other types of treatments.
Ashish Kamat: Great. Now, that's a good point. And the other thing that's coming up recently is you have active surveillance, but then you also have office fulguration, you have chemo ablation, all other ways to de-intensify the treatment. And you've been part of the IBCG's most recent retreat, where we're talking about the ways to address intermediate risk. Share with our audience a little bit your thoughts on where you think office fulguration, chemo ablation, and active surveillance fit in. Not necessarily just for this paper, but in general, what is your thought process for those patients?
Marco Moschini: Well, I think there are several considerations that you need to make when you decide to do one treatment instead of the other, for example, cost, but also the idea of the patient of receiving a treatment or undergoing active surveillance. I would stress on two different points that for me are understudied. One is the ability of the pathologist to correctly diagnose the high-grade tumor or a variant histology, for example.
Because when I start an active surveillance protocol, I really want to have my pathologists giving a report that actually I have from the previous TURBT. Because what I see sometimes when I do a revision of the pathology is that in our series, at least, we had a 20% to 30% of change in the diagnosis because a local pathologist is probably more associated to skipping aberrant histology or skipping a high-grade tumor. And this is something that I don't want, at least for this type of treatment.
And the second part, the second important part that I think is always missing in this kind of discussion is also the willingness of the patients to come and do the follow-up and to do the treatment. And that is not just a follow-up for active surveillance, but also like, for example, doing the maintenance treatment after an induction. Or also for the chemo ablation, if you have a scheme of chemo ablation, that requires also a patient to come and to do the treatment properly, and all parameters that you have to keep in account.
Of course, the laser fulguration, if you have it, it's easier because you just use it, and then you just need to follow-up the patient. But from the other side, you feel more relief because in a way, you already give treatment. So you have to consider all these parameters. I'm trying to build a diagram in our hospital so for all the urologists who just follow the line and follow the diagram. But sometimes it's not so easy to capture all these elements in one diagram. And so sometimes it requires also a little bit of workup with the patient to understand needs and the actual problems.
Ashish Kamat: Of course. Now, I mean, those are great points. But I like what you said at the end because it truly is a patient-centric approach. And it's a shared decision-making between us and the patient. If you could put everything in an algorithm, then we could just have AI run your clinic. You don't need to have Professor Moschini in there with all your wisdom and nuances. So that's very important. It has to be personalized and tailored to each patient. And it's not a cookie cutter, just everybody fits one paradigm. Marco, I want to thank you always for your interest in expanding the field and for taking the time today. Thank you very much.
Marco Moschini: Thank you. Thank you for the invitation.