Sam Chang: Hello, everyone. My name is Sam Chang. I'm a urologist in Nashville, Tennessee, and I work at Vanderbilt University. And we are all quite fortunate to have Dr. Jeanny Aragon-Ching. Jeanny's the Clinical Program Director of GU Cancers at the Inova Schar Cancer Institute in Fairfax, Virginia. And she's going to be giving an updated presentation for what she presented at GU ASCO 2022. And then we'll spend a few minutes kind of asking her and probing her thoughtful mind of where the next steps are going to be in terms of urothelial carcinoma. So we'll start off with Jeanny. Jeanny, thank you so much for spending time with us.

Jeanny Aragon-Ching: Sam, thank you so much and for UroToday, too, for giving us a little bit of insights on the abstract that I presented at GU ASCO.

So this is the treatment and survival differences in patients with urothelial versus non-urothelial bladder and upper tract carcinomas and analysis from the National Cancer Database. And as we all know, bladder cancer occurs in about 81,000 patients, and there is an increased need for learning more about urothelial and non-urothelial cancers because non-urothelial cancers typically have known to be worse prognosis than urothelial cancers. So the objective really of this dataset is to further describe the patterns, demographics, stage, metastasis, and response to chemotherapy and immunotherapy explored through the NCDB.

So this is what we did. It was a de-identified dataset from NCDB ranging from 2004 to 2017. And we used these different histologic terms to define transitional cell or urothelial cell carcinoma versus the non-urothelial cancer cell cohorts. And using chi-square tests, Kaplan-Meier method, and log-rank tests, a statistical analysis to look at the data.

And in total, we had 649,000 patients and as expected, there were more urothelial cancers compared to the non-urothelial cancer patients. Majority of patients were men, as expected, again. Upper tract cancers, 62%, 75% for bladder for men. And median age is actually very similar across the board. Majority were Caucasian men. And interestingly enough, there were more African-American patients in the non-urothelial cancer cohorts, about twice as much, 10.8%, compared to 5.26%.

Now, primary surgery occurred more frequently in the patients with urothelial cancer, 94.7%, compared to the non-urothelial cancer cohorts. And this is the high-level data that we saw. In stage zero and one patients you will see that urothelial cancer patients had a better median overall survival compared to the non-urothelial cancer patients. On the other hand, as stage increases towards stage two and three, as well as stage four cancers, we see that the curves soon to be are overlapping. Whereas on the right-hand side of your slide, you will see the effects of chemotherapy. So effects of chemotherapy on the urothelial cancer cohort certainly is more favorable, median survival's about 73 months compared to only 17 months for the non-urothelial cancer cohorts. On the other hand, immunotherapies affects similarly is more favorable for the urothelial cancer, about 115 months median survival compared to only about 64.5 months.

So in summary, urothelial cancer of both bladder and upper tract origin compared to the non-urothelial cancer cohort tend to have a better prognosis in both presentation, as well as even treatment with chemotherapy or immunotherapy. This highlights the need for better therapeutic strategies for patients with non-urothelial cancers. And with that, thank you so much for your attention.

Sam Chang: Jeanny, thank you so much. I think the presentation, just like every great presentation, just asks many more questions that are out there. So some of the questions I had in mind are, and you may not know this because it's tough sometimes in the NCDB, but were there certain subtypes, and this is dangerous whenever you go back and you try to parse out more, certain subtypes that seem to be worse than other subtypes in the non-urothelial cancers?

Jeanny Aragon-Ching: Yes. And we actually had an earlier dataset that looked at the fine-tuning or details of the non-urothelial cancer subsets. On the other hand, we know that certain histologies, like adenocarcinoma tend to do worse than, let's say, as well as like small cell carcinoma patients, for instance. But to your point, Sam, we have yet to dissect all the non-urothelial cancer cohorts to see which one of the group actually fares a little better than the others.

Sam Chang: And then, did you notice, as you parsed out kind of the urothelial versus non-urothelial and you had different stages, as a group, did the non-urothelial, and you may, again, not be able to tell this, but did they tend to present at a similar stage for a stage or they tended to be later and more progressive in terms of disease?

Jeanny Aragon-Ching: Yeah. It tends to be later and more, and that's what we see in clinical practice too, which is they typically present at the later stage and metastatic for whom the opportunities for early cure unfortunately, is not available to everyone.

Sam Chang: So, as you consider non-urothelial carcinomas... As our medical oncologists struggle with, we don't really know, there's no best set regimen that we know of. And each one may have nuances, a squamous cell versus an anode, versus a small cell. We're basically guessing. In terms of these kind of very small populations, but clearly that do worse, where do you think the next step should be in terms of study? Should we parse them out only for small cell or do we start off with, as a group, non-urothelial? What are your thoughts regarding that?

Jeanny Aragon-Ching: Yeah. Again, by sheer numbers alone, the limitation of the numbers, I think creating or designing a trial that would encompass all of the non-urothelial cancer patients as a catchment, for instance. And of course, several studies come to mind, including ICONIC, which will capture all of the patients with rare GU cancers. And from that sort of basket trial, we can hopefully glean a little bit more on the treatment paradigms and the treatment in general.

And the one thing I would say about the limitation from a lot of these cancer databases is of course the lack of granularity, right? So when we look at the outcomes from chemotherapy or immunotherapy, for instance, there is no real detail about, is it cisplatin-based chemotherapy or toxin base? What about the immunotherapy, what drugs were used? So there's no ability to fine-tune what those treatments are.

Sam Chang: Right.

Jeanny Aragon-Ching: One thing I would also say is the database captured until 2017. So, that was around the time when immunotherapy drugs were starting to first come to the clinic. So there's still a lot of data we have not captured. So I would say stay tuned for more.

Sam Chang: Right. Yeah, I think very interesting would be that from 2017 to say, 2022, these next five years when we really have incorporated kind of standard of care for those patients that are not eligible for chemotherapy, what happens when they get immunotherapy? And we may have already selected out the worst actors early on.

Jeanny Aragon-Ching: Exactly.

Sam Chang: It'll be very interesting. As you look at the NCDV, which is, you just pointed out some of the weaknesses, but it is very real world.

Jeanny Aragon-Ching: Right.

Sam Chang: It captures the data from 70, 80% of the cancer centers, and this is what happens and this is where you go. What is your group's next project? What are you guys interested in looking at and why?

Jeanny Aragon-Ching: Yeah. I think the next project really would be, and there is a lot of interest really in the non-urothelial cancer cohorts, especially because, again, we see time and again, that they are the worst actors, poor prognosis group of patients. And I think developing strategies in order to help them as a whole would be really the next step, using this databases again, as you pointed out, Sam, as a real-world pattern so that we can further glean from this database so that we can apply it to our next generation of clinical trials.

Sam Chang: Last question then, what did you find out about urothelial cancers that you found interesting or unique or different? Because clearly just like you, and I think many others, we're looking at this non-urothelial, because we're trying to gain as much information from that as possible, because we don't have a lot of good information. Was there anything on the urothelial side that you found interesting, intriguing, maybe kind of fodder for the next trial, anything on the urothelial side?

Jeanny Aragon-Ching: Yeah. I do think there may be still a lot of room to evolve with this. So notice that our project actually encompass bladder and upper tract urothelial cancer. And even among urothelial cancers in the GU tract, I do think there is a difference between upper tract and bladder, even amongst the set of urothelial cancers. So I think that would be the next step to further dissect. We know in a lot of big databases, the adjuvant immunotherapy trials, the upper tract patients, even though they are urothelial, they behave differently. And I think that would be very important for us to tease out, because there definitely would be regular differences, behavioral differences, why they act differently or actually behave differently in terms of treatment as well.

Sam Chang: Well, Jeanny, thank you again for spending some time with us and really appreciate all the efforts that you've made. And obviously the folks at GU ASCO also wanted to show their appreciation as you presented it. So thanks again. And we look forward to future projects from your group.

Jeanny Aragon-Ching: Yeah. Thanks for having me here too.

Sam Chang: Absolutely.