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Sam Chang: Hello, my name is Sam Chang, a urologist in Nashville, Tennessee, and I work at Vanderbilt University Medical Center. And we are more than fortunate to have, actually, Dr. Jeannie Hoffman-Censits. Dr. Hoffman-Censits is an associate professor at the Johns Hopkins University School of Medicine at the, yes. I'll stop with that. And we're fortunate to have Jeannie here with us today to talk about the new AUA guidelines on upper tract urothelial carcinoma, that is being presented, or was presented, at the AUA 2023 meeting.

And in looking at the authors of that guidelines, Dr. Hoffman-Censits, you're the only medical oncologist on the panel. So you had a lot of say on what was found, and what was discussed during that kind of process of putting the guidelines together. So tell me first, what did you think of that process of working with the AUA, putting these guidelines together?

Jean Heather Hoffman-Censits: Well, first of all, Sam, thanks so much for the opportunity to sit here with you today, and talk about these guidelines.

Sam Chang: Yes.

Jean Heather Hoffman-Censits: Yeah, it was a wonderful experience, and I want to just thank the chairs of the committee and the AUA for really thinking about this, and putting in the effort and the heart and soul to, I think, bring highlight to upper tract urothelial cancer, and to get these guidelines together. It was a great experience. A lot of discussion about the data that's out there, a lot of retrospective data, but more prospective data more recently. And yeah, it's been great.

Sam Chang: Right. Which is an exciting time. I mean, clearly, the AUA attempts to have evidence-based guidelines. You can only go so far based upon the quality of evidence, as was discussed during the guidelines. And it was important to have a multidisciplinary panel. And so, to have you on there, to be able to discuss the pros and cons of systemic therapy, I think was very, very important.

So let's talk about, from a medical oncologist standpoint, upper tract urothelial carcinoma. Let's say you see the patient first. And obviously, some of these recommendations, a lot will be coming from the guidelines that were just being presented. But say a person sees you first, with a diagnosis of upper tract disease, kind of go through your thought processes, what you're thinking about, the timing, et cetera.

Jean Heather Hoffman-Censits: Sure. Well, typically, patients don't see me first, Sam, but.

Sam Chang: They're referred from outside.

Jean Heather Hoffman-Censits: Referred from, yeah, from urology.

Sam Chang: They saw a urologist in middle Tennessee whose first name's Sam, last name... And they wanted to have an idea of, okay, from a medical oncology standpoint, you've got a small piece, tiny biopsy, because that's all I could get.

Jean Heather Hoffman-Censits: Right.

Sam Chang: And it shows urothelial carcinoma, and it says no evidence of invasion. And it does say some low risk features. Let's say it says low grade and some high grade. Tell me the things you think about.

Jean Heather Hoffman-Censits: Sure. So seeing a patient with upper tract urothelial cancer as a medical oncologist, I think for most general medical oncologists, this is not going to be a common thing that we see. We're more used to seeing patients for a consultation from a urologist for muscle invasive bladder cancer.

Sam Chang: Sure.

Jean Heather Hoffman-Censits: Where we know this is platinum based neoadjuvant chemotherapy, leads to overall survival benefit. And so, really, I think from that perspective, we have that down pat. There's much less information about the upper tract space.

Sam Chang: So I think these guidelines are so helpful. Right.

Jean Heather Hoffman-Censits: Exactly. So helpful. But in addition to less prospective and retrospective information, there's less clinical information. So we come with less staging. So as you mentioned, it's going to be a tiny biopsy. These are not expected to be invasive biopsies. So our usual rules of seeing a muscle-invasive tumor in order to give someone neoadjuvant chemotherapy in bladder cancer, those rules don't apply in the upper tract setting. So if we have a high grade tumor, visible tumor that you can see on imaging, endoscopic biopsy, and a patient planned for a nephroureterectomy, that patient should at least be counseled whether or not they should get neoadjuvant chemotherapy.

So we love the fact that even the plan for a discussion is in the guidelines, to have that discussion. And it's important, because as we know, cisplatin is metabolized by the kidneys, and also potentially toxic to the kidneys. For some of these patients, you have one shot on goal to get chemotherapy into them, because their renal function, in general, is going to drop following surgery. So you go from having a GFR in the 60 to 70 range, where platinum-based chemotherapy may be safe, in the post-op setting, after that nephrou, it may no longer be feasible. And then all of a sudden you might be trying to take care of a patient with a high grade, high risk tumor, lymph node positive disease, and you can't give them chemo.

Sam Chang: And you have limited options at that point.

Jean Heather Hoffman-Censits: You have limited options. Exactly.

Sam Chang: So from a medical oncology standpoint, obviously, so many factors come into play. You mentioned renal function, you mentioned kind of the nature of the disease. Obviously for us, the presence of a solitary kidney versus both kidneys. Lots of questions come into play.

Jean Heather Hoffman-Censits: Yeah.

Sam Chang: And sometimes, things are disparate. So for instance, if you had even a really small tumor that was high grade, but their current EGFR is around 50, that patient, you may normally, if their EGFR was fine, you might consider, okay, they can do nephrou, we can do adjuvant, we can see if they need adjuvant. So tell me kind of the things that really are important to you as you see this patient. What are you looking at?

Jean Heather Hoffman-Censits: Well, of course, I think those patients that you're treating with the idea of curative intent.

Sam Chang: Okay.

Jean Heather Hoffman-Censits: And for chemotherapy, for cisplatin based chemotherapy, we are really talking about those patients that have high grade upper tract urothelial cancer. The size may not matter as much, but for those patients where they're destined for a nephrou, those are the patients where we really want to see them for chemotherapy. Like bladder cancer, upper tract urothelial cancer is a disease where we clinically understage patients. So we get those unhappy surprises following surgery, with positive lymph nodes, or tumors that are a little bit more invasive. And stage for the stage compared to bladder cancer, the outcomes are worse. So I think that this is really important to have those multi-d discussions with urology, with medical oncology, prior to making those decisions. Sometimes we'll see that people will get a biopsy.

Sam Chang: Sure.

Jean Heather Hoffman-Censits: Get some imaging, and then immediately be booked for the operating room. I don't think there's that degree of urgency that there, it's a good chance to take a pause and have discussion about really what are the options, and is neoadjuvant chemotherapy the right thing for this person?

Sam Chang: Right. So let's move away from the guidelines for a little bit. So tell me about the process at Hopkins. In terms of, you're right, most of the patients you don't see up front, it's one of the surgeons who will see. But tell me kind of the process for those patients that are diagnosed with an upper tract in Baltimore.

Jean Heather Hoffman-Censits: Sure. So there's a few different processes, but one of the things that we're really excited about is a new multi Z clinic that we have. So for patients often that are coming for a second opinion, they've already been diagnosed with an upper tract tumor, or maybe have had a ureteroscopy, or two or three, and still don't have a diagnosis for a lesion that's pretty kind of far up into the renal pelvis. So those patients will come to see us, and they're seen at the same time with me as medical oncology, a specialist in a upper tract urothelial cancer from a urology standpoint, as well as radiology at the same time.

Sam Chang: Oh, fantastic.

Jean Heather Hoffman-Censits:
With pathology that kind of comes in beforehand, before the consultation. So we are really excited about doing all that at once. Yeah.

Sam Chang: That's a great model.

Jean Heather Hoffman-Censits: Yeah.

Sam Chang: I mean, because I think the guidelines definitely, and this is the case for the bladder cancer guidelines, this kind of clear realization of the multidisciplinary team effort. I mean, we say that, but to be actually seeing that in motion, and being done at such a place like Hopkins, that's really, really, I think telling, number one, of how important and how effective it is. And number two, hopefully will serve as a role model for other institutions, to help improve the care of our patients.

Jean Heather Hoffman-Censits: Yeah. And it's hard to do that all in person, and we realize that. And so, a lot of times these conversations are happening. We all use Zoom now.

Sam Chang: Sure.

Jean Heather Hoffman-Censits: Some of our tumor boards are in that realm.

Sam Chang: Absolutely.

Jean Heather Hoffman-Censits: And I think different places do it in different ways, but to have that multi-d discussion, however that's happening, is important. I think that's happening more and more with upper tract disease.

Sam Chang: So from a medical oncologist standpoint, as you see these guidelines, and you understand the role of systemic therapy and the timing of it, what is the most exciting, from your standpoint, of, okay, where are we going to go next in the complete treatment of these patients? Is it going to be maintenance therapy, maintenance immunotherapy? Is it going to be, are we going to do different types of targeted agents? What, to you, is the most exciting coming up from a systemic therapy standpoint?

Jean Heather Hoffman-Censits: Sure. I mean, I think for me, Sam, the bar's a little bit low. I'm excited the fact that we're having the conversation about patients with upper tract disease. As someone on the medical oncology side, one of the things that is a bit disheartening is that there still is a lot of variability in the treatment of patients with upper tract disease. We don't see that as much with bladder cancer.

Sam Chang: Sure.

Jean Heather Hoffman-Censits: That's pretty standardized. Straightforward.

Sam Chang: And that took time.

Jean Heather Hoffman-Censits: It took a long time.

Sam Chang: It took time.

Jean Heather Hoffman-Censits: It took a long time time.

Sam Chang: Right.

Jean Heather Hoffman-Censits: Yeah. Remember a decade ago, meetings like this were discussions about the pros and cons. [inaudible 00:09:43] Right?

Sam Chang: No, absolutely. Absolutely.

Jean Heather Hoffman-Censits: Right. Right. So the good news is, we don't have that conversation anymore. And hopefully in another few years, not a decade, we won't be having those conversations about upper tract urothelial cancer. But I think to have some streamlined consistent guideline based approach to these patients, I am super excited about that.

Sam Chang: Yeah.

Jean Heather Hoffman-Censits: Because I think that we'll be seeing patients that are getting the best care that they can no matter where they are, based on these guidelines. We have the opportunity to give neoadjuvant chemotherapy based on some prospective data, some from our group, some from Jonathan Coleman's group at Memorial, which is awesome. We have, of course, the POUT trial from Europe.

Sam Chang: Sure.

Jean Heather Hoffman-Censits: Alison Birtle and her colleagues, showing that post-operative chemotherapy beneficial for those high-risk patients. And then of course, as you mentioned, the opportunity too, to give adjuvant immunotherapy for patients maybe that had pre-operative chemotherapy. And we see biologically, boy, this tumor did not respond to pre-operative chemotherapy.

Sam Chang: This is bad tumor, B-A-D.

Jean Heather Hoffman-Censits: Yeah. This is bad news. And then we have a second opportunity to give immunotherapy in the post-op setting for those patients.

Sam Chang: So the number of options, I think, is amazing. And with the last question, I do want you to mention, you are working on starting a trial in upper tract disease with systemic therapy. So give us kind of a little Reader's Digest version of that.

Jean Heather Hoffman-Censits: Sure.

Sam Chang: Before it starts opening up widespread.

Jean Heather Hoffman-Censits: Sure. So this trial is really for a population of patients, our colleague, Surena Matin, cause these, let's see, guideline ignored in trial ineligible patients who... Because urothelial cancer is a disease that can come back over time to see a patient with high risk, high grade, upper tract urothelial cancer, and either one kidney or really poor kidney function, and then to tell that patient, well, the standard of care is a nephrou, and you need to go on dialysis or have such poor kidney function.

Sam Chang: And there're more of those patients than-

Jean Heather Hoffman-Censits: There's a lot.

Sam Chang: Exactly. They are-

Jean Heather Hoffman-Censits: There's a lot. Yeah.

Sam Chang: They don't fit our little algorithms very well.

Jean Heather Hoffman-Censits: They don't. They don't. And when this comes up, I think we're always constantly, of course, having a discussion in tumor board and talking about what is the standard. But I think each time, we're still having that discussion about what's the best thing for those patients? And as far as I know, we really don't have prospective data. So this is a trial with a goal of replacing the idea of surgery for those patients, the majority of whom, who don't want surgery, with systemic therapy. So we have a combination of chemotherapy and immunotherapy for those patients. Hopefully, that trial will be opening soon.

Sam Chang: Oh, that'd be great.

Jean Heather Hoffman-Censits: Still working on some behind the scenes paperwork, but.

Sam Chang: No. Yeah. Because clearly, just as I said, there are many more of those patients than we would like to admit.

Jean Heather Hoffman-Censits: Yeah.

Sam Chang: This is not a common tumor. But when it occurs, and there have been retrospective studies show that this is not usually a healthy population.

Jean Heather Hoffman-Censits: No.

Sam Chang: They've had exposures, many to tobacco. Their age tends to be older. So this is a high risk population from not a necessarily disease standpoint, but from an overall kind of patient performance status standpoint.

Jean Heather Hoffman-Censits: Yeah, exactly. I know. We're talking about perioperative chemotherapy for these patients, but we know about half of those patients that we see in the office don't qualify. The average age of our population, they're in their 70s.

Sam Chang: Yes, absolutely.

Jean Heather Hoffman-Censits: So this is a, it's a tough road sometimes. Yeah.

Sam Chang: Yeah. But to have something kind of codified in guidelines from the AUA for the first time, I think, is really an important first step.

Jean Heather Hoffman-Censits: It is.

Sam Chang: Thank you so much for your help, and in helping to formulate these AUA guidelines. And as always, whenever I spend any time with you, always learn so much, and appreciate your efforts. You're the best. Appreciate it very much.

Jean Heather Hoffman-Censits: Oh, thank you. You too. No, it's been my pleasure and honor to try and better serve this population of patients, and to talk about them with you today. Thank you.

Sam Chang: Great. Thanks.

Jean Heather Hoffman-Censits: Thanks.