Zachary Klaassen: Hi, my name is Zach Klaassen, urologic oncologist at the Georgia Cancer Center. We are at AUA 2025 in Las Vegas. On UroToday, I'm pleased to be joined by Doctor Pratik Kanabur, who is a urologic oncologist at UCLA. Pratik, thanks so much for joining us on UroToday.

Pratik Kanabur: Absolutely. Thank you. Glad to be here.

Zachary Klaassen: You have some really important and exciting data you presented at AUA, looking at the cost‑effectiveness analysis of zirconium‑girentuximab, which is a new PET imaging agent for identifying small renal masses from the clear cell histology. So before we get into the great results from your study, maybe just give us a background highlight of the unmet need of molecular imaging in these patients.

Pratik Kanabur: Absolutely. So when you're talking about small renal masses, T1 masses, it kind of falls into two different categories. The first is overtreatment. We're diagnosing these masses earlier, more often. There's been an epidemic of full‑body MRIs. So we're trying to figure out what to do with these small renal masses.

Trying to figure out if it's cancer or it's not is a difficult task. CT/MRI can only do so much. Sensitivity is about 70% or so. There have been some likelihood scores, called the Clear Cell Likelihood Score, that maybe improve it to about 75%, but still not optimal. And despite our best interests and doing surgery, 20% of these masses can be benign after surgery. So that's a difficult task.

The flip side is undertreatment of masses. So we're undergoing surveillance, but maybe not everyone's a good candidate. We do know that patients who have clear cell or adverse histology can develop metastatic disease even at smaller sizes. So it's important to really distinguish and find the tumor biology. So I think this is where molecular imaging can really help and figure out if there's a better sensitivity to pick up these masses and figure out who should be treated and who should not be treated.

Zachary Klaassen: Yeah, great background. That kind of leads us into the ZIRCON study, which was presented a couple of years ago now at GU ASCO and then subsequently published in Lancet Oncology in 2024. Just highlight briefly what that trial showed, inclusion criteria, and then the diagnostic characteristics.

Pratik Kanabur: Absolutely. So the ZIRCON trial was a phase III, open‑label trial. It looked at patients who were suspected to have clear cell cancer and who were T1 masses, so less than 7 centimeters. It was a resect‑and‑see trial, meaning the patients were already scheduled for partial nephrectomy or radical nephrectomy. And the PET scan was compared to the pathology from review.

What it showed is two important things. The first is that there were no adverse safety events, so no issues with the girentuximab PET scan or the tracer. The second thing is the results compared to CT—the sensitivity was about 86%. Specificity was about 87%. And that significantly outperformed the CT scan. And it didn't change for the size of the mass, even less than 2 centimeters, bigger than 4 centimeters. So it's pretty sensitive and accurate. And it's a good noninvasive tool for these patients.

Zachary Klaassen: Yeah, great summary. Getting into the trial design of your guys' cost‑effectiveness analysis from the UCLA cohort, just set us up with the study design of what you guys looked at.

Pratik Kanabur: Absolutely. So it was a cost‑effective analysis, and I'd like to first thank my colleagues at Johns Hopkins, Tony Su and his mentors, Nirmish Singla and Mohammad Allaf, and then my mentor Brian Shuch and colleague Hiten Patel, who were all instrumental in this idea and analysis.

So this is a cost‑effective analysis comparing three different arms. The first is a reference, meaning everyone gets surgery. The second is patients get a biopsy. If it's positive, they have surgery. The third is they get the TLX250 PET scan. If it's positive, they undergo surgery. If it's negative, we surveil. And the third or fourth arm is they get the PET scan. And then, if it's negative, they'll follow by the biopsy.

Zachary Klaassen: I see.

Pratik Kanabur: So what our analysis showed is that first doing this, the third arm, meaning you do the PET scan followed by the biopsy, had the greatest proportion of leaving benign masses untreated and had the lowest proportion of malignant masses left untreated, meaning we're capturing the patients that really need the surgery based on this model.

The second thing is that it showed that this arm, the PET scan followed by biopsy, was cost‑effective, looking at the cohort. And the third thing is if you vary all the probabilities and parameters and costs, if you are willing to pay $100,000 per quality‑of‑life improvement, which is what's commonly used in health economic analysis, it showed that this arm was beneficial compared to doing biopsy or partial nephrectomy empirically.

Zachary Klaassen: That's great. That's a good explanation. Some of these results are hard to interpret for the audience. You did a great job of explaining that. When I think about—there's a lot to unpack from this, and the one that I really honed in on was the fact that when we think about mixing biopsy—and there's people that don't biopsy anybody. There's people that biopsy everybody. And there's a lot in between. Your study basically shows that if it is a negative TLX250 scan, that's when we should maybe consider biopsy. Is that fair?

Pratik Kanabur: Yeah, I think that's fair. I think that in terms of health economic analysis, it's really important to know that any sort of noninvasive test is always going to be kind of cost beneficial. There have been studies that look at clear cell likelihood scores that are usually cost beneficial. And then my colleague Tony Su showed that for the sestamibi scan, it was sestamibi followed by biopsy. That was also cost‑effective. So it's important to know that anything that you do is noninvasive.

And yes, the idea is to do this PET scan. And if it's negative, then you perform a biopsy. What's important to know is that the trial, this data from this study, looked at clear cell likelihood possibility. But we do know that this PET scan can pick up CA9, which can be expressed even in papillaries and other tumors that have pseudohypoxia. So it's important to know. So maybe doing biopsy might enrich for benign masses or indolent masses. So the biopsy may be kind of a rule‑out system. I don't think it's still going to be an important toolkit in the urologist workup of these masses.

Zachary Klaassen: Absolutely. It's been a great discussion. Maybe just a couple of concluding or take‑home messages for our listeners.

Pratik Kanabur: Absolutely. Thank you so much for having me.

Zachary Klaassen: Of course.

Pratik Kanabur: I think three important points are I think this is going to be—or three kinds of case scenarios I can see this to be used for. The first is for these small renal masses. We have patients who come in with multiple scans or who have an unclear scan. I think this is a good scan to say kind of a yes or no, and kind of work them way to the threshold.

I think the second is to maybe use for larger or locally‑advanced renal masses to see if we can find metastatic disease earlier. And then the third is in patients who have metastatic or who had the radical nephrectomy, this may be able to detect it earlier and figure out what the best therapy, whether it's adjuvant or systemic therapy for them.

So it's exciting to see where all the case scenarios are. Our analysis was about small renal masses, but I do think this PET scan will be helpful for all different kinds of patients with kidney cancer.

Zachary Klaassen: Yeah, absolutely. There's a lot of ways that we're going to incorporate this into our practice following a pending, hopefully, approval of this agent. So again, thank you for joining us. Awesome discussion.

Pratik Kanabur: Absolutely. Thank you so much for having me.