Pedro Barata: Hello, everyone. Welcome to another video at UroToday highlighting data being presented around renal cell carcinoma. Today, we're being joined by Dr. Brian Shuch, a leader in the field leading the program at UCLA in California. Brian, thank you so much for joining us once again.

Brian Shuch: I appreciate it, Pedro. Thanks for the invitation.

Pedro Barata: Absolutely. So we've talked about this topic before. We're talking about novel imaging. Maybe the first time we'll see PET scanning playing an important role in patients with renal cell carcinoma. So conventionally, we tend to say that we don't really use a lot of PETs beyond prostate cancer for GU malignancies and that seems to be changing and that's due to your amazing work or your leadership within girentuximab PET scanning against carbonic anhydrase IX. A target overexpressing clear cell RCC. I want to congratulate you, because the data and the project that you submitted to SUO really was awarded one of the top 30 abstracts and then of course, followed a presentation, so congrats for that. There's a lot of good data presented in that meeting and one of the highlights was really the data you submitted there, so congrats. I want to take the opportunity to have you here to actually talk a little bit about it, because the way I understand from getting your presentation and from the conversations that follow, it's really a unique approach. So just for those who don't know, and I'll let you explain how you did it, but basically, you have shown us all in the ZIRCON trial that actually you're able to have high sensitivity, high specificity using this girentuximab anti or finding the CAIX for undetermined renal masses.

And you got that experience from a number of sites really around the world and you got that experience. And so that's what made you embark on this effort of getting different sites, different teams from different specialties and trying to answer the question, okay, how is this impacting our life in the management of undetermined renal masses in the daily basis? Instead of me using my own words, I want you to explain this. Is that it? Can you walk us through what did you do or how you coordinate those teams to present this data?

Brian Shuch: So for ZIRCON, it was a large 300 patient trial looking at patients who had imaging and then resection. It basically established that the tracer could detect clear cell kidney cancer and hopefully, we'll see what happens with the FDA review in the next few months. The question is you diagnose something as clear cell kidney cancer. So what? Or if you say it's probably not clear cell kidney cancer, so what? So we don't have real-world data yet on how this actually impacts management. So we did have obviously 300 cases that had patients who had imaging available, had detailed history, had detailed laboratory evaluation and then had the PET-CT and we were able to use that and basically simulate cases for clinicians to decide how they were going to use that information. And clearly, it's retrospective, but it's a way to simulate patient management. So for this study, there were people who worked on the ZIRCON trial who had a multidisciplinary like a tumor board situation where every site would have two urologists, they would have a nuclear medicine specialist and were encouraged to have a radiologist.

A lot of programs had radiologists and nuclear medicine people who were one. But there were four centers and they were basically given all this information, how they wanted to manage a patient with the available information, with the caveat that these patients in ZIRCON did go for surgery, but everyone was independent in their decision-making. So basically, patients were presented, each team had a multidisciplinary discussion and as a team, they would have to decide how they were managed. And it could be either a biopsy, additional information like a SPECT-CT. It could be going for a partial nephrectomy or radical nephrectomy, going for potentially an ablation or SBRT based on the clinical scenario. Now, once the teams decided what they want to do, we waited a month to simulate, hey, we're going to order a scan and then we're going to get the scan results and we're going to see this patient back in our clinic. Clearly, sometimes you decide to do something and then a month later, your opinion can change, but usually, we're pretty certain and we don't really change by random chance. So we basically compared what happened with our decision-making four plus weeks later from before and after amongst those teams. And not surprising, there was change in management in about 48% of the cases, so looking at before and after using that information did change how the teams wanted to approach that patient's care. And things like deciding whether to do a node dissection, no node dissection, it's considered a minor change whether you're going to do things robotic or laparoscopic or transperitoneal or retroperitoneal.

Those are minor changes, but deciding whether you're going to basically do a radical or partial, do an ablation, do a biopsy, those were more major changes, so about 48% did change management and of those, three-quarters were considered major changes. And a lot of these patients had either escalation or de-escalation. So sometimes we were going to do a biopsy. 21% of biopsies were considered omitted. And then there were a lot of patients who actually had treatment escalation. If you had a complex five centimeter mass and you know it's clear, so maybe you think it's a little bit more aggressive. Maybe you would do a radical nephrectomy, or if the scan was negative, maybe you're going to do a biopsy. So we did see a lot of management changed and I think this is going to help highlight that this tool is going to basically have change in management. And I've been saying all along, we're going to manage patients ZIRCON hot one way and ZIRCON cold another way, because we have different biology in those buckets.

Pedro Barata: So I love that summary, Brian. It's really a proof of concept. And by the way, there's almost 300 patients, I believe, that you presented in this work, where you actually find these changes in management, which it's a pretty significant number of changes. And as you said, some of them are actually very, very relevant and highly impactful, I guess, in patients' lives, if you will. And I also like the fact that you're already suggesting probably in the near future, we'll see a change in the management.

Brian Shuch: Correct.

Pedro Barata: Using PET imaging to actually differentiate. So I would love to see a study having that premise to provide prospective validation of it. So I guess that's my question to you, Brian. What do you think we need to see and as you are so in-depth in this field, what do you think the further efforts are going to look like in terms of further studies that might be able to confirm these findings in a prospective manner?

Brian Shuch: So we have a prospective ongoing expanded access program and frankly, it's been so hard to keep up with you, Pedro, because you put everyone you see on a trial. So I don't know if we're ahead of or behind you, but there's been about 300 patients on that prospective expanded access trial and they are recording change in management. And again, that's not published yet, but there's a lot of patients in many of our experiences that change management in the real world. So I think that's going to be further validation that this does impact management. Again, when we don't have head-to-head trials comparing ablation and partial nephrectomy or a biopsy or no biopsy, patients really should just be offered what is considered a standard of care, but we have lots of standard of care. And I try to tell patients, "We need to get you the most information to make you to make the most informed decision for your treatment." This is another tool and I'm hoping that it'll be available in a widespread fashion in the US and beyond, where we can offer patients more information, because not every patient is going to be the perfect candidate to just rush off to surgery. We have more tools available to help them guide their management.

Pedro Barata: So this is super, super helpful, Brian. This is amazing. I'm really looking forward to seeing the next steps, as you mentioned, for the expanded access and also the ongoing trials. I know you are doing investigator-initiated studies and looking into this in different settings as well and it sounds like we will have to adapt to a new way of managing these patients. So I'm looking forward to see what our regulatory agencies have to say about it probably in the next several months and go from there. Brian, thank you so much for taking your time. Congratulations for leading those efforts. Truly, truly important, really impactful in the field and thanks for sitting down with me and talk about this important topic.

Brian Shuch: Perfect. Thanks, Pedro.

Pedro Barata: Thanks.