Long-Term Survival Outcomes in Patients with BCG Unresponsive Non-Muscle Invasive Bladder Cancer: Evaluating Bladder-Sparing Treatment - Wei Shen Tan
May 11, 2023
In this conversation, Wei Shen Tan joins Ashish Kamat in discussing findings on BCG unresponsive bladder cancer patients, comparing bladder-sparing treatment and early radical cystectomy. The study they discuss shows no difference in overall or cancer-specific survival, suggesting a bladder-sparing approach may be suitable for selected patients. However, early salvage cystectomy is recommended if bladder-sparing treatment fails. The discussion highlights the importance of case selection and prompt treatment for high-grade recurrence. It also emphasizes the need for emerging data on second and third-line bladder-sparing approaches for selected patients.
Biographies:
Wei Shen Tan, MD, PhD, FRCS (Urol), Urologic Oncology Fellow, Department of Urology, MD Anderson Cancer Center, University of Texas, Houston, TX
Ashish Kamat, MD, MBBS, Professor, Department of Urology, Division of Surgery, University of Texas MD Anderson Cancer Center, President, International Bladder Cancer Group (IBCG), Houston, Texas
Biographies:
Wei Shen Tan, MD, PhD, FRCS (Urol), Urologic Oncology Fellow, Department of Urology, MD Anderson Cancer Center, University of Texas, Houston, TX
Ashish Kamat, MD, MBBS, Professor, Department of Urology, Division of Surgery, University of Texas MD Anderson Cancer Center, President, International Bladder Cancer Group (IBCG), Houston, Texas
Read the Full Video Transcript
Ashish Kamat: Well, welcome Wei Shen Tan to UroToday and thank you for taking the time and spending it with us today to discuss all the work that you're doing in bladder cancer. For those of you that may not know, Wei Shen Tan is currently a fellow at MD Anderson, but comes with a long history of involvement with bladder cancer. And first off, let me say, it's been a pleasure to have you at MD Anderson, working on our team. So tell us a little bit about the abstract and the podium presentation that you had at the AUA, talking about patients with BCG unresponsive disease and their long-term outcomes.
Wei Shen Tan: Thank you very much Dr. Kamat, for your kind introduction and mentorship. So essentially what I presented today was looking at patients with BCG unresponsive, non-muscle invasive bladder cancer. And what we did was we compared outcomes between patients who underwent a bladder-sparing approach treatment versus early radical cystectomy. And what we found was that there was no difference in overall survival, as well as cancer specific survival with a long-term follow-up of a median of 70 plus months or so.
We also did some further analysis comparing patients who received early cystectomy versus the late cystectomy. And again, we found no differences in overall survival and cancer specific survival. The median time to cystectomy, in the early cystectomy cohort, was about two months and it was about 12 months for the delayed cystectomy. So what we concluded was that, in this study of BCG unresponsive patients at MD Anderson for over a 20-year period, in a selected group of patients, particularly patients without lymphovascular invasion and without variant histology, they may be suitable for a bladder-sparing approach. However, it is important to appreciate that an early salvage cystectomy, following failure of a bladder-sparing approach, is indicated to preserve survival benefit.
Ashish Kamat: So share with us a little bit your thoughts as to why this question was important. Why did you look at this question?
Wei Shen Tan: It's pretty important, because radical cystectomy, while it is the standard of care in muscle invasive bladder cancer, a lot of patients might be quite reluctant to undergo radical cystectomy for non-muscle invasive bladder cancer. And very often patients seek out bladder-sparing approaches. And although there have not been enough data... Historically, there is not sufficient data to recommend a bladder-sparing approach for BCG unresponsive, there's emerging data today to suggest that there are alternatives, although high grade recurrence rates still remains high, indicating that, again, early salvage cystectomy, it would be important to advocate if a patient would continue to pursue a bladder-sparing approach.
Ashish Kamat: One of the fears we've had when we were designing the initial studies with pembrolizumab, with the nadofaragene and all of the others that are currently emerging with N-803 and CG0070 and many others, was are we losing that window of opportunity for care for our patients by advocating that they go on these clinical trials? Based on what you've found, what would your answer be at this point?
Wei Shen Tan: I think based on our retrospective data, it's safe to say that in well-selected group of patients, you don't compromise survival outcomes when a patient would elect to go for a bladder-sparing approach. So it's emerging data and we will add to the building evidence, which suggests that it is reasonable to try these approaches rather than do early radical cystectomy for everybody.
Ashish Kamat: And you also looked at the issue of early salvage cystectomy, as you said, after the patients have tried to have bladder-sparing therapy and it hasn't worked for them. Can you shed some light as to how you might recommend our viewers use that data to counsel their patients, that want to try treatments forever? Where they come and say, "Well, I tried drug one. Now I want to try drug two. I want to try drug three.". How would you suggest that the patients and us use that data to counsel patients?
Wei Shen Tan: I think case selection is very important. So if you've got varying histology, you've got high risk factors, you've got lymphovascular invasion, it's important that these cohort of patients might be best served with an early radical cystectomy to begin with. The other thing is also to be aware that in our cohort actually, a lot of patients had following failure of a trial, of a bladder-sparing approach. They went on to a radical cystectomy, so that about 40, 50% of patients would continue to develop high grade recurrence. And it's important to promptly treat these patients to preserve their survival, to preserve oncological outcomes. We don't have much data from our analysis to suggest that what happens if they go on to a second, third line bladder-sparring approaches. So it's quite important that hopefully that there'll be emerging data to support that in selected patients.
Ashish Kamat: And that's a critical point that you made. One of the things to remember is that when we design clinical trials, these patients are excluded. Patients at variant histology, lymphovascular invasion, they're excluded from participating in these trials. So we can't really take the results of the clinical trials, in patients that are pure, and then apply them to the general population that has these high risk factors that you talked about. So that's a very important point that you raised. Thank you again for taking the time and being here with us on UroToday. In closing, any high level thoughts from your abstract that you want to leave the audience with?
Wei Shen Tan: Thank you very much. So, in summary, in well-selected group of patients, particularly patients without lymphovascular invasion, as well as without variant histology, it is reasonable to attempt a bladder-sparing approach, important to appreciate that the risk of high grade recurrence continues to be quite high even after bladder-sparing approaches. So an early salvage cystectomy is important to preserve oncological outcomes.
Ashish Kamat: Excellent. Thank you so much.
Wei Shen Tan: Thank you very much. Thank you.
Ashish Kamat: Well, welcome Wei Shen Tan to UroToday and thank you for taking the time and spending it with us today to discuss all the work that you're doing in bladder cancer. For those of you that may not know, Wei Shen Tan is currently a fellow at MD Anderson, but comes with a long history of involvement with bladder cancer. And first off, let me say, it's been a pleasure to have you at MD Anderson, working on our team. So tell us a little bit about the abstract and the podium presentation that you had at the AUA, talking about patients with BCG unresponsive disease and their long-term outcomes.
Wei Shen Tan: Thank you very much Dr. Kamat, for your kind introduction and mentorship. So essentially what I presented today was looking at patients with BCG unresponsive, non-muscle invasive bladder cancer. And what we did was we compared outcomes between patients who underwent a bladder-sparing approach treatment versus early radical cystectomy. And what we found was that there was no difference in overall survival, as well as cancer specific survival with a long-term follow-up of a median of 70 plus months or so.
We also did some further analysis comparing patients who received early cystectomy versus the late cystectomy. And again, we found no differences in overall survival and cancer specific survival. The median time to cystectomy, in the early cystectomy cohort, was about two months and it was about 12 months for the delayed cystectomy. So what we concluded was that, in this study of BCG unresponsive patients at MD Anderson for over a 20-year period, in a selected group of patients, particularly patients without lymphovascular invasion and without variant histology, they may be suitable for a bladder-sparing approach. However, it is important to appreciate that an early salvage cystectomy, following failure of a bladder-sparing approach, is indicated to preserve survival benefit.
Ashish Kamat: So share with us a little bit your thoughts as to why this question was important. Why did you look at this question?
Wei Shen Tan: It's pretty important, because radical cystectomy, while it is the standard of care in muscle invasive bladder cancer, a lot of patients might be quite reluctant to undergo radical cystectomy for non-muscle invasive bladder cancer. And very often patients seek out bladder-sparing approaches. And although there have not been enough data... Historically, there is not sufficient data to recommend a bladder-sparing approach for BCG unresponsive, there's emerging data today to suggest that there are alternatives, although high grade recurrence rates still remains high, indicating that, again, early salvage cystectomy, it would be important to advocate if a patient would continue to pursue a bladder-sparing approach.
Ashish Kamat: One of the fears we've had when we were designing the initial studies with pembrolizumab, with the nadofaragene and all of the others that are currently emerging with N-803 and CG0070 and many others, was are we losing that window of opportunity for care for our patients by advocating that they go on these clinical trials? Based on what you've found, what would your answer be at this point?
Wei Shen Tan: I think based on our retrospective data, it's safe to say that in well-selected group of patients, you don't compromise survival outcomes when a patient would elect to go for a bladder-sparing approach. So it's emerging data and we will add to the building evidence, which suggests that it is reasonable to try these approaches rather than do early radical cystectomy for everybody.
Ashish Kamat: And you also looked at the issue of early salvage cystectomy, as you said, after the patients have tried to have bladder-sparing therapy and it hasn't worked for them. Can you shed some light as to how you might recommend our viewers use that data to counsel their patients, that want to try treatments forever? Where they come and say, "Well, I tried drug one. Now I want to try drug two. I want to try drug three.". How would you suggest that the patients and us use that data to counsel patients?
Wei Shen Tan: I think case selection is very important. So if you've got varying histology, you've got high risk factors, you've got lymphovascular invasion, it's important that these cohort of patients might be best served with an early radical cystectomy to begin with. The other thing is also to be aware that in our cohort actually, a lot of patients had following failure of a trial, of a bladder-sparing approach. They went on to a radical cystectomy, so that about 40, 50% of patients would continue to develop high grade recurrence. And it's important to promptly treat these patients to preserve their survival, to preserve oncological outcomes. We don't have much data from our analysis to suggest that what happens if they go on to a second, third line bladder-sparring approaches. So it's quite important that hopefully that there'll be emerging data to support that in selected patients.
Ashish Kamat: And that's a critical point that you made. One of the things to remember is that when we design clinical trials, these patients are excluded. Patients at variant histology, lymphovascular invasion, they're excluded from participating in these trials. So we can't really take the results of the clinical trials, in patients that are pure, and then apply them to the general population that has these high risk factors that you talked about. So that's a very important point that you raised. Thank you again for taking the time and being here with us on UroToday. In closing, any high level thoughts from your abstract that you want to leave the audience with?
Wei Shen Tan: Thank you very much. So, in summary, in well-selected group of patients, particularly patients without lymphovascular invasion, as well as without variant histology, it is reasonable to attempt a bladder-sparing approach, important to appreciate that the risk of high grade recurrence continues to be quite high even after bladder-sparing approaches. So an early salvage cystectomy is important to preserve oncological outcomes.
Ashish Kamat: Excellent. Thank you so much.
Wei Shen Tan: Thank you very much. Thank you.