Sam Chang: Hello everyone. My name is Sam Chang. I'm a urologist in Nashville, Tennessee. I work at Vanderbilt University. And I am incredibly privileged today, as all of you are, to have Dr. Jeanie Hoffman-Censits from Johns Hopkins University. Dr. Hoffman is in fact, the co-director of the upper tract urothelial carcinoma multidisciplinary clinic at Hopkins. And as all of you're aware, she is truly a leader, when it comes to evaluating, treating, and actually studying, upper tract urothelial carcinoma.

And so this morning, I've asked her to actually talk a little bit about this multidisciplinary clinic. We, at Vanderbilt, don't have that clinic, and I think a lot of places don't. So I was going to ask her first, tell us about the clinic, Jeanie, and how did you guys develop it? And why is it so important to those patients with upper tract disease?

Jean Hoffman-Censits: Sam, first of all, good morning. Thank you so much for the opportunity to talk to you.

I think one of the things that we've recognized, that I've recognized as a medical oncologist, who has a lot of interest in upper tract urothelial cancer, and has had the pleasure of seeing these patients in clinic, is that they often, number one, sometimes don't completely even understand their diagnosis when they come to us. I've had more than a few patients come in, thinking that they have kidney cancer because someone maybe drew a picture of the kidney or something like that. Part of this program that we have, a clinic as well as a program, is having a home for patients to come to that have upper tract urothelial cancer.

We have, not only a clinic presence, where patients are seen by a medical oncologist, it's me, a urologic oncology specialist, Dr. Singla, as well as a typical pathology review, as well as radiology review. But we actually have a great online presence as well, for patients to go to, to get in for information about upper tract urothelial cancer. We found that, when patients are trying to find information on the internet, having a cancer diagnosis, it's scary in and of itself. And then, to search the internet, not really find anything that has anything about your diagnosis, is very isolating. So we wanted to rectify that, and have our team and our clinic as a home for those patients.

Sam Chang: So with the urologists usually, usually, not always, but usually diagnosing these patients, who do you think, should all upper track patients be in this kind of setting? Or are there patients that you all tend to focus on more than others? And if so, why?

Jean Hoffman-Censits: Yeah, sure. So as you know, just like in lower tract urothelial cancer, a lot of these tumors are low-grade tumors. So as a medical oncologist with the toolkits that I have, systemic chemotherapy, immunotherapy, and targeted therapy, there's less of a role really, or no role, that we currently have necessarily, for those patients. That might change in the future. But sometimes, I feel like patients often are seeing enough specialists sometimes that, especially for the low-grade patients, I don't see as much of a role for a medical oncologist. There are so many topical therapies, as well as new and exciting trials coming around. Certainly, if patients want to see a medical oncologist, we're happy to do a consult. But for the most part, from the multidisciplinary perspective, we're focused on patients that have high-grade upper tract urothelial cancer.

Sam Chang: And so for these patients, there's been obviously, a big renewed interest, or perhaps a first-time interest, with published trials, actually showing an advantage to adjuvant chemotherapy in patients who undergo nephroureterectomy. But as with clinicians always, we're quick to say we need more study. And when the study's done, we're quick to say, well, that wasn't the right study to do. But the nice thing about that, it does initiate other studies. Are there studies currently, that are enrolling, that you find interesting or promising?

Jean Hoffman-Censits: Yeah. And actually, even before we talk about those studies, I think it's really important just to point out the fact that we're having the conversation. That we're talking about the fact that the POUT study is out there, and shows a benefit in adjuvant chemotherapy. That team completed a randomized Phase III trial in upper tract urothelial cancer. Let's celebrate that. Let's talk about that for a second.

Sam Chang: Absolutely agree with you.

Jean Hoffman-Censits: It's so important.

Sam Chang: Absolutely, 100% agree with you.

Jean Hoffman-Censits: Thank you. Right.

Sam Chang: Yes.

Jean Hoffman-Censits: I think that so much focus is debating where should the chemotherapy be? Let's just hang on for a second, that we've completed a Phase III study. It's so important. And I think part of the issue with patients that have upper tract urothelial cancer, they're often in a subgroup analysis. So we're trying to gather data in ways that we really shouldn't. So the fact that we are now designing clinical trials, answers these important questions. That we're having debates, that we're having sections at big meetings, talking about upper tract disease. That's the big success for science and for patient care. That's a big success.

Sam Chang: I think I agree with you absolutely. In that, it's always easy to throw tomatoes but to actually complete these, to complete this trial, is absolutely laudatory. It deserves praise, and not complaints and concerns. So as patients with high-grade disease, they come to your clinic, and in terms of evaluation, how do you go through the process of someone who has a newly diagnosed high grade, high-risk, upper track lesion that, let's say, doesn't have any concerns of any disease outside of the confined renal pelvis or ureter? How do you guys analyze things? Do you lean towards clinical trials? Do you lean towards following the POUT data? What do you guys look at?

Jean Hoffman-Censits: Yeah. I think like maybe a lot of places in the US, we, of course, are extrapolating some of our data and some of our practice, from using cisplatin in the neoadjuvant setting, for patients with high-grade bladder cancer, where neoadjuvant cisplatin-based chemotherapy improves overall survival. There are special considerations in people who have upper tract disease. There's typically a lot less tissue to work with. And as you know, these are really challenging patients to clinically stage. But stage for stage, they tend to do worse in patients with bladder cancer. And so, at least in our practice, we do generally have a multidisciplinary discussion with those patients. We have open ECOG-ACRIN 8192, which is our large Phase III neoadjuvant chemotherapy study of dose-dense MVAC, compared to dose-dense MVAC plus durvalumab, that's looking at a primary survival endpoint, but also at a pathologic CR endpoint.

Jean Hoffman-Censits: And so, we do talk to patients about preoperative chemotherapy. Depending on the patient, there may be special circumstances where, either from a patient perspective or from a medical perspective, we favor adjuvant chemotherapy. But for the most part, we're at least having a discussion about neoadjuvant chemotherapy. And then, whether or not that's on or off trial, really is dependent again, on the clinical situation.

Sam Chang: Well, let me ask you about the patient that we also struggle with bladder cancer and lower tract disease. Someone that we have concern about regional lymph node disease. So we have someone within enlarged nodes. We give neoadjuvant chemotherapy. There's been a response. And there's some debate, although I think we've definitely shifted towards, if there's a response, that we be as aggressive as possible, proceed with a radical cystectomy, with a lymph node dissection. In upper tract disease, I don't know if there's been a tendency to do that. Yes or no.

Sam Chang: Tell me your thoughts of local-regional control. If you see someone that you've got enlarged nodes, unclear if they're metastatic or not, is that a patient you clear, or perhaps, steer towards neoadjuvant treatment? Or is that someone that you would want actually, nephroureterectomy, and the lymph nodes, to know what exactly we're dealing with? And I know it's individualized, in terms of how the patient is, performance status, and renal function, and other things. But tell me what the mindset is at Hopkins, for those types of patients that have beyond locally confined disease.

Jean Hoffman-Censits: Yeah. Sam, I think you just described a patient that we see a lot in tumor boards. And I think that it becomes really challenging to make decisions as to... I almost feel like we need to update the word metastatic, because there's metastatic and then there's metastatic. Right? There's a surgically resectable lymph node-positive cancer, versus something where a tumor has moved outside of the region, and really, surgery's off the table. I don't know about you. I think a lot of us are becoming more aggressive about that local regional kind of disease. Where we might talk to a patient about a past for frontline chemotherapy, and then local therapy based on how they do, if you see significantly lymph node shrinkage. And I think a lot of us would be very worried about that clinical situation and want to do everything we can to provide good control.

Jean Hoffman-Censits: I think that you brought up really, an important point too, in the treatment of high-grade upper tract disease, which is a lymph node dissection. I think that is another discussion that is had a lot. And sometimes, we'll see patients with a high-grade tumor, that don't have a lymph node dissection. I think that becomes challenging when you're thinking about how to treat them in the adjuvant setting.

Jean Hoffman-Censits: And also an important place in the community for clinical trials. Because it lays out a path for what we all believe should be standard of care. Which is, at least in a clinical trial setting, getting a biopsy, to prove that somebody has an upper tract tumor. Being able to see something on a scan. And then also, performing a lymph node dissection. Those are three components of ECOG 8192, that you are mirroring good clinical standard of care, that I think then, definitely continue that narrative in this trial, and maybe others in the future, as well.

Sam Chang: So let's take that, and let's make this your final point, in terms of recommendations then, for medical oncologists. As a medical oncologist evaluates a patient for upper tract disease, there are obviously, lots of factors that you take into account as you determine the next best steps. To you, are there certain disease characteristics that make you more worried, versus less worried, about individuals? Be it volume, be it previous lower tract disease. Are there certain things that make you say, "Wow, we really need to have this patient have some kind of systemic therapy." Certain clinical characteristics, that medical oncologists, as well as surgeons, know about, as they see and treat these patients.

Jean Hoffman-Censits: Yeah, well, I think like you brought up, lymph node-positive disease would definitely be an important consideration for chemotherapy. The other is, of course, kidney function. So we know from the POUT data, that postoperative chemotherapy is a perfectly reasonable path, that will lead to disease-free survival with platinum-based chemotherapy. But the issue is, is that number one, not everybody can tolerate that. So if someone has a borderline kidney function with a creatinine clearance in the 50s, prior to surgery, with two kidneys, then it's unless they have a completely nonfunctional kidney, that's going to come out. That patient really might not tolerate platinum-based chemotherapy in the postoperative setting. So that really has to come into play, when you're having those kinds of discussions with patients. But I think clearly, perioperative chemotherapy is an important component for patients with locally advanced T2 and higher disease.

Sam Chang: Well, Jeanie, thank you so much for spending time with us. And I do really want to applaud your efforts, and the efforts at Hopkins, in terms of actually forming a multidisciplinary clinic, specifically for this disease type. That's just, I think, part of the evolution, and part of the growing understanding. That these tumors, even though small in number, the type of therapy you choose can really be impactful, in terms of how these patients do.

So thank you again. And I personally applaud to all your efforts, and all the efforts at Hopkins, as well.

Jean Hoffman-Censits: Thank you. Thanks for your time. It's great talking to you.

Sam Chang: Thank you.