Radical Cystectomy vs Trimodal Therapy for Patients With Localized Muscle-Invasive Bladder Cancer - Stephen B Williams

Stephen B Williams and his team explored the question: What is the association of patient survival and intensity of treatment with total Medicare costs that are associated with radical cystectomy vs trimodal therapy for older adults with localized muscle-invasive bladder cancer in a time Fram of longer than 180-days? He and Alicia Morgans discuss the study, its findings, and implications in patient care. The objective was to compare the 1-year costs associated with trimodal therapy versus radical cystectomy, evaluating survival and intensity effects on total costs.

Dr. Williams explains the findings that compared with radical cystectomy, trimodal therapy was associated with higher costs among patients with muscle-invasive bladder cancer. The differences in costs were largely attributed to medication and radiology expenses associated with trimodal therapy. Extrapolating cost figures resulted in a nationwide excess spending of $468 million for trimodal therapy compared with radical cystectomy for patients who received a diagnosis of bladder cancer in 2017.

Biography:

Stephen B. Williams, MD Assistant Professor in Urology, Tenure-Track, Robert Earl Cone Professorship, Director of Urologic Oncology, Director of Urologic Research, Co-Director Department of Surgery Clinical Outcomes Research Program

Alicia Morgans, MD, MPH, Associate Professor of Medicine in the Division of Hematology/Oncology at the Northwestern University Feinberg School of Medicine in Chicago, Illinois.
Read the Full Video Transcript

Alicia Morgans: Hi. I'm delighted to have you here with me. Today, Dr. Steven Williams, who's the Chief of Urology and the Director of Urologic Oncology at the University of Texas Medical Branch at Galveston. Thank you so much for being here.

Stephen Williams: Well thank you for inviting me today.

Alicia Morgans: Of course. So I really wanted to talk with you about a recent [JAMA] surgery paper that your team has published. So first, kudos. That's an amazing journal of high impact. Really exciting. But the reason that you were published in JAMA Surgery is because you had a really high impact research project. And it was looking at patients who had cystectomy versus patients who had trimodality bladder-sparing therapy. And really trying to understand their outcome, particularly survival and some economic outcomes in these populations. And I'd love to hear you talk to us about that project and that high impact paper. 

Stephen Williams: Absolutely. So what we ended up looking was a large national database called Sierra Medicare. And specifically we looked at the time period between 2002-2011, and what we wanted to do was compare radical cystectomy versus trimodal therapy and looking at survival outcomes, but also importantly, costs that are associated with these treatments. 

And what we ended up using as a propensity score match, a statistical methodology to match those two cohorts. And essentially determined survival outcomes, overall cancer-specific, as well as costs. And in doing so, we ended up identifying worse overall in cancer-specific survival associated with trimodal therapy. However, greater than $300 million dollar increase in costs that are associated with trimodal therapy. 

Now caution needs to be made when interpreting this information because it's a retrospective study. There may be inherent selection bias that we can't account for, considering its retrospective nature. And then, in addition, sensitivity analyses were performed to hopefully control for potential confounders. But we can't control for unknown confounders. And in doing so, what's interesting is that patients that received neoadjuvant chemotherapy and radical cystectomy, when compared to trimodal therapy, had even more improved survival outcomes. 

Alicia Morgans: Wow. Tell me a little bit about this. Because I think in our center, it's actually two distinct groups that end up getting trimodality therapy. There is a highly-selected group that gets chemo, radiation, followed by close follow up with the urologist for this typical trimodal therapy that mimics that, that we see in the clinical trial experience. And these patients are being treated for cure, and that is our intent and that is our hope. Highly selected. So no hydronephrosis, and really not multifocal disease. And usually, decent performance status. And again, our goal is for a cure. 

And then there are patients who get essentially trimodality therapy. But the reason is, they're not going to be candidates for cystectomy. They either have more extensive disease. Maybe they have hydronephrosis, but again, can't get surgery. But there are other factors, just as you mentioned, these confounders, that are not necessarily going to be included in a Sierra Medicare database that would lump those patients plus our patients with intent to cure into a single trimodality bucket to be compared with the surgical patients. 

And I just want to hear how did you control for that? Or sometimes we can't, and so we just have to read the paper knowing that there's that limitation, but also knowing that the data is what it is and it's really important as it stands. Go ahead.

Stephen Williams: You're absolutely correct. And as you were discussing that, I just felt this urge that I wanted to explain things further. And through another sensitivity analysis, we can't identify dosing of chemotherapy. But what we did try to do is identify fractions delivered and median fractions delivered. Which in this JAMA paper was approximately 17, which we all know would be inferior in regards for our primary trimodality treatment for bladder cancer.

However, there are limitations in regards for determining the fractions delivered that you may not be able to identify all the fractions. But when we did that, despite those results, is those that had increased greater than 17 median fractions delivered had improved survival in the trimodality cohort, however, were still inferior in survival outcomes. 

We've done a follow-up study to this that the findings will hopefully be published soon where we actually improved our identification of the fractions delivered, which is approximately 27 fractions. And although we did identify the 27 fractions delivered, it still resulted in inferior survival outcomes overall in cancer-specific among the trimodal therapy patients. 

Alicia Morgans: Okay. Well and one of the other things that you mentioned before we really sat down was that what's also really interesting is that the survival benefit that we see with the surgery as compared to the trimodal therapy included patients in that surgical cohort or group who did not have neoadjuvant chemotherapy. Which as a medical oncologist, I know that there's a nice amount of data that suggests that neoadjuvant chemotherapy is going to improve survival for those patients after cystectomy, of course, combined with cystectomy. 

So it might be that the difference, at least in the cohorts that you used in this study, would be even greater if there wasn't such underutilization in neoadjuvant chemotherapy. So again, I'd love to hear your thoughts there.

Stephen Williams: You're absolutely correct. And as we know, there's underutilization of neoadjuvant chemotherapy, in so much as there's also underutilization of radical cystectomy in the treatment of bladder cancer. But specifically answering your question, the sensitivity analyses that we did identify when we did the neoadjuvant chemotherapy with radical cystectomy compared to the trimodal therapy when looking at survival outcomes, there's even a greater discordance, if you will. 

But also too, we performed a cost analysis in this subsequent study that we're ongoing and doing right now where we identified, although there's increased costs associated with trimodal therapy, when we actually critically assessed comparing the neoadjuvant chemotherapy combined with radical cystectomy versus the trimodal therapy, we actually identified no difference in those costs. Which is important I think in today's day and age when we're considering costs, what are the components of those costs, and the increased costs that are associated with, particularly with the administration of chemotherapeutic agents and the treatment of cancer, specifically bladder cancer. 

Alicia Morgans: Okay. So really, if we look at all else being equal, if we use chemotherapy plus radical cystectomy, the cost is actually quite similar to the chemoradiation trimodality therapy? 

Stephen Williams: Correct. However, a caveat in this is, as there often are in these retrospective studies, we didn't look at the types of neoadjuvant chemotherapy that was delivered. And in a prior study that we've done with Dr. Kamat and myself, it was also one of the co-investigators in these studies, is that there's underuse not only of neoadjuvant chemotherapy but the quality. Where approximately 50% of patients that of those 14 or 11% that get neoadjuvant chemotherapy actually get the guideline-recommended chemotherapy.

Alicia Morgans: Well it sounds like there's a lot of work to be done. And I really look forward to seeing the updates by your group. I'd love to hear your closing thoughts on the multi-disciplinary approach. Because whether it's neoadjuvant chemotherapy and cystectomy or trimodality therapy and bladder sparing in highly-selective populations, working together I think is something that's really important, at least in my practice, to improving outcomes for bladder cancer. And I'd love to her your thoughts on that.

Stephen Williams: Absolutely. And it must be known that it was actually my radiation oncologist that prompted a lot of these studies. But that's kind of the open dialogue that us as providers that we have. That I think you bring an important point, that as a multi-disciplinary clinic. And at my institution where I also have learned from my training at MD Anderson, and then at Brigham Women's is the incorporation of not only the urologist but radiation oncologists, medical oncologists. But even beyond just the treatment of cancer, but treatment of the patient. 

Psychological services, in addition hospice care. And really encompassing and embracing not only the management of the cancer, but more importantly, the management of the patient. 

Alicia Morgans: I love that message. And we will definitely close on that. And thank you so much for your time.

Stephen Williams: You're very welcome. Thank you.
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