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Zach Klaassen: Hi, my name is Dr. Zach Klaassen. I'm a urologic oncologist at the Georgia Cancer Center in Augusta, Georgia. And we're here in San Francisco at GU ASCO 2024. I'm delighted to be joined by UroToday's good friend, Dr. Steve Williams from UTMB Galveston. Thanks so much for joining us, Steve.

Stephen Williams: Well, thank you so much, Zach and the UroToday team. Always a joy to be here, and we're going to have some fun.

Zach Klaassen: Absolutely. So you've become really the expert in comparing radical cystectomy to trimodality therapy for muscle-invasive bladder cancer. So just walk us through what you found over the last decade or so and then introduce the genesis of the work that you presented this weekend.

Stephen Williams: Sure. Well, as you know, it's a team effort. So I've had really just a great journey working with medical oncologists, radiation oncologists, urologists, but then even economic experts to really just understand this disease. And as you know, bladder cancer is the most costly disease historically and doesn't include the even recent introduction of IO therapies and so on. So as you know, we've initially investigated this using large population-based data, primarily from SEER Medicare and found inferior outcomes with trimodal therapy versus radical cystectomy. But then what was more intriguing is the substantial costs that are associated with trimodal therapy, largely driven by medications, pharmacy as one can contribute, but also to the radiation radiology costs. So in doing so, we've done some further studies trying to tease out the nuances. There's always selection bias and one could debate the survival components and whether or not there is a difference. But really the costs are quite substantial really for either therapy, which is approximately median cost could be upwards of 300,000 to even 400,000 with trimodal therapy.

Zach Klaassen: So in this recent work, you've looked at SEER Medicare in the past, use a different database for this study. Tell us about that database.

Stephen Williams: Sure. So, what we didn't want to do was do another repeat SEER Medicare study. No one needs any more of those, right? So we wanted to use the Optum database, and this is really important because we understand from a Medicare beneficiary, but we don't know non-Medicare beneficiaries. And whether or not that does impact. Also too, we wanted to increase our cohort, so we use the Optum database, which is from 2015 to 2023. So it's actually really the most recent data that one can garnish. And we looked at the cost, but also the outcomes describing these once again and between the two. And we can't control for selection bias. And this database though doesn't have central pathology. Neither does SEER Medicare per se, but this does lack actual detailed pathologic characteristics. So we did use surrogates to try to control for that component, but really it's exciting because we get to look at the non-Medicare beneficiaries as well.

Zach Klaassen: So basically, to clarify for some of our folks that maybe don't live in the US. Medicare, older patients, more than 65 and Optum's encompassing everybody. Correct?

Stephen Williams: Correct.

Zach Klaassen: Yeah, that's great. I think when we see trends in signals like we did with SEER Medicare, it's important to validate it. And you're validating it in a completely different cohort based on age as well, correct?

Stephen Williams: Correct.

Zach Klaassen: What did you guys find? What was sort of the key takeaways from the study?

Stephen Williams: Well, interestingly enough, going off that backdrop, the median age ended up being roughly about 70 years for either the TMT group, trimodal therapy. If I say TMT, that's what I'm referring to. It is slightly older and obviously more sick than the radical cystectomy candidates. But what's more intriguing is not just the survival but really looking at the costs. And we wanted to focus on the economic contributions. And up to five years, trimodal therapy had substantial increased costs. The median cost per patient was about $400,000 versus approximately $200,000 to $250,000 for radical cystectomy patients. What's even more intriguing is in our SEER Medicare data only approximately 11 to 14% of patients received neoadjuvant chemotherapy prior to radical cystectomy. We know historically it's underused, but that's pretty substantial. This cohort actually 25% or a quarter actually received neoadjuvant chemotherapy, which is more common in more recent years as one would expect.

But that was quite surprising as well. And then the trimodal therapy actually, we looked at and used our prior lessons learned. Is it palliative radiotherapy or is this another group that we're really trying to compare apples to apples best possible? Median fractions, I believe, were upward of 30 fractions, 36 fractions, if I stand correct. So these are, one would consider, primary trimodal therapy patients that we're comparing to. And parsing out those data, it was actually quite exciting because it's really an external validation of our primary findings. And we didn't go through the necessary statistical hurdles, propensity score modeling and whatnot, because we just wanted to provide a description of the costs of comparing those two treatments.

Zach Klaassen: So some really nice data looking at specific costs. What were some of the more expensive either treatments or follow-ups that you guys found for both?

Stephen Williams: Sure. Well, if we look at time points, I think that's always important when we're comparing costs. And then costs are one nuance of it, but then we didn't look at fixed or variable costs, just costs that are associated with the diagnosis of bladder cancer. So in the first three months following either treatment, then we found that increased inpatient costs were largely contributed to radical cystectomy, one would expect. But then outpatient costs were really the leading drivers for either. And particularly for the trimodal therapy, it was pharmaceutical medication as well as radiology or radiation costs, which is important because we got a target and intervention to decrease these costs aside from, we didn't look at guideline recommended treatments and so on. But really highlights, we need to have some cost containment. And once again, this is just for chemotherapy. We didn't investigate IO reduction. And I know at ASCO GU, there's a lot of very provocative data from survival, and I'm quite certain though, as they do in the UK, we'll be also comparing the cost-effectiveness, a lot of these novel treatments. And really a disease that's already really costly.

Zach Klaassen: And that's a great lead into my next question. So if we take a very high level view at this, if I'm not mistaken, you have a new position or relatively new is leadership position in the hospital, CMO. So you're sitting at your desk and you have all these costs. How do we filter this into the day-to-day practice in terms of cost-effectiveness, being good stewards of care, resources, et cetera?

Stephen Williams: Well, I like to refer to Peter Drucker... What is it? Breakfast and strategy. And I think we have to focus on really leaning towards a culture. And I also have a position medical director, high-value care at our organization. And I've learned so much from that position because working with numerous stakeholders, including our patients, everyone's becoming more aware in an environment where that wasn't necessarily, I wasn't taught in training. And then certainly on my arrival, I didn't sense that on the pulse of the organization and not like we're trying to cut costs here and there. If something is of value to the patient to improve outcomes and is appropriate, then sure. So I think really engaging the stakeholders, our physicians, the front line in a lot of these decisions and really having them develop, and not just physicians. It could be pharmacists, it could be even administrators, which some like to always say are always trying to cost cut.

But I think if you involve those that are actually doing the work themselves, they could tell you and likely decrease variability, reduce waste, and ultimately decrease costs. So I think that's important. And patient selection criteria as at your center, we have a multidisciplinary clinic or environment. I like to say it's now perhaps more virtual, which I think is better in my opinion, that I often interact with my radiation oncologist and oncologist colleagues. And we have that discussion not only on the appropriateness of treatment but then looking at the context of the patient, their disease, and then really the cost of the system. Because with our thin margins that we're coming across in the US, this is so critical as we want to hire more physicians, more staff members and so on and so forth, we have to take ownership in that.

Zach Klaassen: Yeah. It's already an expensive disease. So these kinds of studies certainly give us food for thought. And as always, great discussion. Is there anything we haven't hit on, any take-home messages for our listeners out there?

Stephen Williams: I think one of the joys I've found is not doing the studies myself, but now I've passed on the baton, if you will, to the next generation. So there are individuals that were fellows, now attendings, they're developing these studies. That's the future. And I'm glad I perhaps was a pebble in a pond that just threw it in there and have stimulated really a new generation, if you will, that is really going to challenge our system and improve it. So creating that type of mindset has been a true joy, and I really hope that, and I've seen it here at ASCO GU, a number of other investigators share that same thought. So that's been truly rewarding in this path for me.

Zach Klaassen: Awesome. Well summarized, always a pleasure, Steve. Thanks so much.

Stephen Williams: Thank you.