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Sam Chang: Hi everyone. My name is Sam Chang. I'm a urologist at Vanderbilt. And I have the great fortune to be joined by Dr. James, AKA Jed Ferguson, who is an Assistant Professor of Urology at the University of Alabama at Birmingham campus, and the medical center there. He is a rising star in the field of bladder cancer.

He and his group recently published an evaluation of the National Cancer Database, looking at how treatment delivery varies, depending on certain profiles, certain factors. And it really, I think, was quite telling in terms of what may influence the reception, or patients actually getting different types and levels of care.

So Jed, first of all, thank you so much, and really admire everything that you've already done in such a short career, and look forward to you sharing some of your findings.

J.E. Ferguson: Well, thank you so much, Sam, and I'm just flattered for the opportunity. And yeah, this was really kind of an eye-opening finding that I'll share, and excited to kind of share that with all the viewers.

The general idea around this is, the question is, why don't more patients with muscle-invasive bladder cancer receive potentially curative treatments? And this was based on a... In general, muscle-invasive bladder cancer is an aggressive cancer, with about 60% survival at five years, despite aggressive and life-changing treatments, such as cystectomy with urinary diversion, chemoradiation, or trimodality therapy, or TMT.

Historically, there were a few studies that looked at this back in the early 2000s, 2010s, John Gore, a group from ACS, and then Sima Porten at UCSF, and using it. Steven Williams also had a nice paper on this. But all of them, with NCDB or SEER, or other databases, saw a significant proportion of muscle-invasive bladder cancer patients not getting cystectomy or aggressive treatment. And so, we were hopeful that that had changed and improved with time, but weren't sure, and that was really the goal of this paper.

So just to introduce the team, the first author is Sol Moon. He's a current UAB urology resident of PGY-4, and actually applying for urologic oncology fellowships as we speak. Vishruti Pandya was assisting Sejong Bae with UAB biostatistics. Andrew McDonald's, a radiation oncologist here on our team. He was a medical oncologist here. Just wanted to make sure we had all the stakeholders involved in all the different treatment modalities. So really excellent team and very helpful.

In case you don't know about the National Cancer Database, it's a nationwide database representing about 70% of incident cancer diagnoses in the US. So when we looked at this database, we found about 102,000 patients with non-metastatic resectable muscle-invasive bladder cancer diagnosed between 2009 and 2018, which was the last date that would have been fully updated from a data standpoint in the database.

And just to cut to the chase, overall, in these patients, 26.6% received no further treatment for their muscle-invasive bladder cancer after TURBT. And an additional 13% received chemotherapy only, which we know is a suboptimal treatment for muscle-invasive bladder cancer. So, in sum, a total of 41% received what we called non-aggressive therapy. And when we combined cystectomy and radiotherapy to represent aggressive therapy, only 55% of the patients received them.

When we did a multivariable analysis to try to understand what variables were associated with not receiving aggressive therapy, just some of the things that you would expect, including age, high comorbidity score, Black race, certainly wouldn't expect that. But underinsured status, and then presence at non-academic and low-volume centers. And this is Figure 2 from the manuscript, basically showing, in orange here, breaking it down by decade of age. The number of patients getting observed goes way up, as you would expect, in those greater than 90 years old. And for surgery, in blue, that correspondingly decreases significantly. The numbers at risk are down here at the bottom.

So when you look at age, older patients, greater than 70 years old, made up the majority of patients not receiving aggressive therapy. So in this pie chart, this is greater than 90 patients in their 80s and patients in their 70s, but over 30% of these patients were under the age of 70, which historically has kind of been well within the wheelhouse of patients that you would think would be candidates for cystectomy from an age perspective.

Other findings included, we looked at the utilization of perioperative chemotherapy over this time, and it increased, when you looked at cystectomy patients, from 17% to 47% by 2018. So a huge increase in neoadjuvant chemotherapy utilization, which I think is a huge win, and shows that medical oncologists and urologists are really improving and responding to guidelines. And then, the utilization of trimodality therapy increased over this timeframe from 5.4% to 8.8%, so almost double. Which, if they're not going to get cystectomy, I think trimodality therapy is certainly a good potentially curative option. So that was encouraging.

In terms of conclusions, the utilization of aggressive therapy for muscle-invasive bladder cancer, I would say, has basically not improved over the last 20 years. In general, patients not receiving aggressive therapy are older, sicker, and more likely to be cared for in low-volume centers in the community.

Black patients, which make up about 7% of this cohort, are 30% less likely to receive aggressive treatment after controlling for other variables. So this is a major disparity that deserves further attention.

We looked at rates of treatment refusal or ineligibility between Black and non-Black patients and didn't see any difference. Although, I would say that these variables in this database are not quite as accurate as something more granular. Finally, at least 30% of patients not receiving aggressive therapy are relatively young, as defined as age less than 70.

So, I think the important questions are how we can improve on this? We've seen this over the last 20 years, but we're really not changing anything, and I think we need to do better on that.

Most importantly, we need more granular data from registries to better understand why this is and what we can do about it. But with the majority of these patients getting care at community and low-volume centers, it's going to be difficult to study efficiently, which is probably why it hasn't been done already. So I think we need to really put our heads together and see how we can get that data efficiently.

Next question is, are these patients getting high-level counseling about aggressive therapies, including trimodality therapy? And if they're in the community, do they have access to a radiation oncologist? Do they have access to a high-volume cystectomist? And if not, can telehealth play a role to facilitate the consultation? I think that's an interesting question that we can now start to ask in the post-COVID era with the explosion of telehealth.

Next, are patients refusing therapies, and if so, what concerns do they have? Would any further patient education help, or are continent diversions being discussed? Again, I think this is where having additional consultations with high-volume cystectomists and radiation oncologists may really help.

And finally, are there access to care or travel issues to tertiary care centers? And for patients with low resources, can we leverage community resources better?

So that's all the findings I had, and at that point, I'll-

Sam Chang: I'd like to focus on that last slide first, because clearly the three that were pictured on your slide are much brighter than the two individuals that the viewers are now going to be looking at. So I applaud you on that. That's number one.

Number two, these are very thought-provoking, and clearly, the buzzword of hypothesis generating, there's no question. The first thing I take away from this is, knowing that the National Cancer Database covers about 70% of patients that are treated for cancer, they tend to be, to be part of the NCDB, you need to meet certain requirements. You need to fill out forms. You need to keep up with patient outcomes. You need to stage patients. I would think that even those, that 30% not covered, the level of care, if anything, may be even worse.

J.E. Ferguson: Absolutely. Yeah.

Sam Chang: So it is quite sobering. So let's take your last point in the future directions. The distance to travel, the distance to get to tertiary care, driving to a big city, etc. We have struggled with this. I know the folks in Birmingham have, I know the people in Nashville. People struggle with that travel. What do you think are our next steps? How can we improve this access to care from first a geographic standpoint?

J.E. Ferguson: Yeah. I don't have a good answer for that.

Sam Chang: I don't think anybody does.

J.E. Ferguson: Yeah. I think telehealth is a possibility. But to be honest with you, a lot of these patients have bad Wi-Fi, and they don't have access.

Sam Chang: No Wi-Fi.

J.E. Ferguson: ...to the internet.

Sam Chang: Or no Wi-Fi. Yeah.

J.E. Ferguson: Yeah. And they may not have a smartphone. So I think there have been some studies that suggest that telehealth actually worsens disparities, then improves them. So I throw that out there briefly, but I think when the rubber hits the road, it might not be the fix that we all hope it would be. Maybe having some docs travel there periodically to offer consultations in person would be one way, kind of an outreach program. But people are so busy that it's going to be hard to make that work.

Sam Chang: I think almost by default, people have written about centers of excellence. John Gore has used that term, centers of excellence, and whether or not we need to actually define that. And if you look at, I've had discussions on this podcast actually with Manish Patel from Australia, who has helped set up exactly that system in that country, which also has geographic demands of very vast areas of travel that are required, and has basically started to establish that. In the US, do we make the next step of really identifying, hey, if you have invasive bladder cancer, these are the places you need to go? Like I said, it's already happening by default, but do we need to really, not necessarily mandate that, but really advocate that as a medical community? Controversial question. I hate to put you on the spot, but it's something to really consider, especially with data like you present.

J.E. Ferguson: Yeah. I think you can make a strong argument for that. On the flip side, just to play devil's advocate, I wonder if we... There's this feeling, I think, among community urologists that cystectomies are, they're complicated patients. A lot of comorbidities. And I've heard, I'm not as worried about in an RVU system, I'm not worried about reimbursement, but the payment structure just doesn't pay well to take care of patients with invasive bladder cancer. But, if you can incentivize them and make it worth their while, and train doctors in the community to perform cystectomy on these rare patients where they can't make it to the center of excellence because of travel issues or whatever, then maybe that increases the number of patients receiving cystectomy. But they're going to be doing one or two a year. So from a volume perspective, it doesn't set up well, but maybe it's better than nothing.

Sam Chang: I mean, there's no correct answer. And so much has been done regarding, and this data actually supports that, the higher volume centers, et cetera, higher volume surgeons tend to do better, but that's not an absolute. Some of the busiest hospitals and surgeons sometimes have, actually, some of the worst outcomes, and those that just do a few may have, actually, quality outcomes. So if we do set up any type of center of excellence, I think we're going to have to actually have quality measures, not base it totally on volume, but have some quality measures. And what those quality measures are, that's always the big question for anything that we do in medicine.

I want to then end with the disparities. I think your data regarding chemotherapy use and its improvement, I think you're absolutely right. We've done a fairly good job of starting the groundswell of understanding the importance of multidisciplinary care. And I think there's a ceiling to pre-op chemotherapy. Many individuals may not be eligible, may refuse, may have neuropathy, heart issues, et cetera, that may preclude, renal function issues. But that number rising, as well as the trimodal therapy using basically bladder-preserving strategies. I think that also increasing shows a better realization of what should be done. So I am encouraged with some of your findings for sure.

It is discouraging about the two things, that significant percentage of under 70, 30% plus not getting definitive care, be great to be able to dive into those numbers. And then the risk, independent of other variables, that Black race led to a significant decrease in the chance of actually getting curative, or potentially curative treatment. So I think just if you said, Sam, Washington, others, the folks at UCSF, Sima and others, have started looking at this, and trying to tease out what is leading to this. But I definitely think that's an area where we're starting to recognize it, which is the start. But now the question is, what do we do? How do we educate, change, alter practice? So would like to know what your thoughts are about that.

J.E. Ferguson: Yeah. We just need more granular data, a lot more granular data. Our levels of Black patients are higher than average here in Birmingham. So something that we are interested in looking at. But if you really want to drill down into this specific subset of muscle-invasive bladder cancer patients that are not receiving cystectomy, I suspect it's going to be a hard patient population to really pin down and study carefully. So the numbers are likely to be pretty low, and multidisciplinary collaborations are going to be important.

Sam Chang: Your point, I think, is a really good one because there are clearly individuals who never get to us, never get to the medical oncologist, and that true denominator, we really don't know. All the ones that we see, and those that we see, may have different reasons for not pursuing care, totally independent of their disease process, and it's hard to capture that.

I remember, we attempted to try to do a study on why patients got certain urinary diversions. And we ran into exactly the same kind of issue: there were patients that never pursued cystectomy because they were worried about their diversion. And then the ones that got the diversion, is it surgeon dependent? What's going on? So many different possible variables. When it comes to this type of therapy, it may be as simple as the patient may not want it, to the cost of treatment, to "I've lived a good life." All these different things will be hard to capture, but it is kind of sobering regarding the differences associated with race, as well as the lack of possible curative care for those that you would think age-wise would benefit. So this is great.

Jed, where do you go next in terms of research? What are you guys interested in doing next, based on this data?

J.E. Ferguson: Well, I'd love to get a registry together, kind of a rapid case assessment registry, multidisciplinary, multi-institutional registry. Now I'm picking up the phone and sending some emails to see who would be interested in doing that.

The challenge with that, again, is just the relative lack of these patients at academic medical centers. How do you reach out to community groups? I even looked at the VA numbers, kind of nationwide VA, and it really functions more of a community-type practice. But it would take the top 33 highest volume muscle-invasive bladder cancer centers to average one of these patients a year, per center. Per center. So it would be 33 patients over a year, if you captured all of them.

Sam Chang: Got it.

J.E. Ferguson: So it's just an incredibly daunting thing. I actually reached out to John Gore, who, he and Angela Smith, did a nice job with the CISTO registry for non-muscle-invasive BCG-exposed patients, and are proposing a muscle-invasive bladder cancer study looking at this patient decision-making with cystectomy versus trimodality therapy, and I think including a no-treatment or observation-only arm in that. And then they have all the chops to really get at the patient-level questionnaires and motivations. So, I think that is something that I'll keep pounding John about.

Sam Chang: No, I think that would be very, very telling. Very, very important. And it's rising academic researchers and leaders like you that will help answer these questions.

And I want to thank you for spending some time with us today. But more importantly, thank you for your efforts. Your early career success at UAB is something of note, and I look forward, like I said, to future findings and future research. Thanks so much, Jed.

J.E. Ferguson: Thank you, Sam, I appreciate it. Thanks for the spotlight.