Zachary Klaassen: Hi, my name is Zach Klaassen, urologic oncologist at the Georgia Cancer Center and I'm delighted to be joined on UroToday by Dr. Tim McClure, who is a urologist and interventional radiologist at Weill Cornell Medicine up in New York. Today we're going to be discussing Tim's SNMMI presentation, looking at CAIX-PET imaging and the shift toward precision diagnostics in renal cancer. Tim, thanks so much for joining us on UroToday.

Timothy McClure: Thanks for having me. It's great to be here.

Zachary Klaassen: So just a very high level view for our listeners. By way of background, why do we need high quality molecular targeted imaging for small renal masses, in your opinion?

Timothy McClure: We all know that the incidence of small renal masses is increasing, and we're increasingly seeing that in our practice, and the limitation with imaging as it stands now with standard cross-sectional imaging like MRI, CT or even ultrasound, is that we really can't differentiate cancer from non-cancer tumors. And so it creates a conundrum both for patients and us as urologists, to help manage and recommend treatment options for these patients. And ultimately, unfortunately, it has led to a lot of overtreatment for kidney cancer where there's a study that looked at patients who underwent partial nephrectomy for small renal masses, and a third of those were for benign tumors. And so we need better ways to help stratify patients to either be put on surveillance or be recommended for more definitive treatment like surgery. So that's really why we need better imaging, and with current imaging, even with advanced MR techniques or sequences, we still can't do a good job to reliably diagnose kidney cancer, particularly clear cell kidney cancer.

Zachary Klaassen: Yeah, absolutely. I think too, I mean the family physicians are seeing it. We're seeing it in the ER. They're all coming to us. We're sorting through comorbidities, age, size, all these things. I mean, every urologist in the country is seeing small renal masses. Right?

Timothy McClure: Right, right. And it is tricky because sometimes you'll see a one-centimeter tumor in a 50-year-old and is surgery the best option for them? Or you'll see a four-centimeter tumor in an 80-year-old with a lot of comorbidities, and they're stressed out thinking that they need to have surgery, when in reality surgery is probably not the best option for them.

Zachary Klaassen: Yeah, absolutely. No, that's great. Tim. I think from a biological rationale for CAIX antibody-based PET imaging, such as with 89Zr-girentuximab, what's the rationale for this combination for kidney cancer and small renal masses?

Timothy McClure: Sure. Well, we all know that there are numerous types of kidney cancers. There's clear cell, chromophobe, oncocytoma, all these different types of tumors, but the real tumor that we're worried about is clear cell because that's probably the one with the highest oncologic risk of really posing true oncologic risk to our patients. And so in clear cell, CAIX is overexpressed in these tumors, so that's why they developed the girentuximab to target that CAIX component of clear cell and basically specifically look and identify clear cell kidney cancer.

Zachary Klaassen: Excellent. It's been a couple of years now since the Lancet Oncology publication of ZIRCON, which really sort of put girentuximab-based imaging into the limelight. Maybe just give our listeners a high level overview. What was the objective of that study? What were the key findings from the ZIRCON trial?

Timothy McClure: The ZIRCON study was a fantastic study. Brian Shuch was the lead author, and this was a prospective multicenter international phase three trial that looked at 300 patients who were going to go to the operating room for a clinical T1 tumor, so a tumor less than seven centimeters, and they compared the imaging to ground truth, which was histologic pathology. And the primary endpoint was defining the sensitivity and the specificity of CAIX imaging to basically diagnose clear cell kidney cancer. And they had quite good results for the whole cohort, meaning tumors up to seven centimeters. The sensitivity was 85% and the specificity was 87%. So really good results, and when they did subanalysis for smaller tumors, the sensitivity actually increased to about 97%. So really, really good imaging outcomes with regards to defining or identifying clear cell carcinoma. And I think that because of this study, this imaging tool will really be helpful, particularly in helping us recommend treatment options for patients with small renal masses.

Zachary Klaassen: Yeah, absolutely. And I think too, if we fast-forward now, that trial and the data is part of the application to the FDA. Still pending approval as of August 1st, 2025, but let's fast-forward to approval and just tell us about where you could potentially see this in your practice. Maybe a couple of clinical scenarios where this could be really helpful for either active surveillance, treatment, et cetera.

Timothy McClure: Yeah, so I think if you look at the AUA guidelines where a lot of the recommendations on small renal masses is trying to help determine oncologic risk, and I think that this is going to be a great tool to help us better identify those patients. So I think I will use it personally for the younger patient with a small 1.5 to 2 centimeter tumor who really isn't that keen on surgery and is considering ablation or surveillance as an option. And I think this tool is a great way to help pinpoint the direction of treatment or surveillance because if it comes up negative, I'm going to feel very comfortable putting that patient on surveillance. And I also think the frequency with which we'll need to image patients will decrease from three to six months to maybe start at six months and then extend that out, knowing that you have a negative PET, whereas if it's positive in a young patient, that's a clear indication to move forward with surgery.

And I think it'll help us better identify those patients. Sometimes those patients want biopsies, they get worried about bleeds, et cetera, so I think that'll be useful from that perspective. So that's kind of the younger patient. In an older patient with comorbidities, where you're worried about just risk of surgery because of either history of strokes or heart, coagulation or renal function, this will be a great tool to help better stratify patients if surgery is a good option for them, or even if ablation is an option for them from that perspective, again, because if it's positive, that suggests that that oncologic risk of these tumors growing is real and they probably do warrant treatment.

Then potentially too, I mean, in my practice, we see a lot of pre-transplant evaluations and I think that's another good tool to help us feel more confident about following these smaller tumors. Kidney transplant patients oftentimes have these indeterminate subcentimeter, pericentimeter growths on their kidney, that in reality probably can be safely watched, but oftentimes need surgery just because of the transplant clearance process. So I can see us using this tool as a potential way to help stratify patients who need surgery and who can be safely watched from that perspective.

Zachary Klaassen: That's a great point. We've had a couple conversations with folks about this topic, and I haven't heard that one and actually it makes a lot of sense. We have a big transplant center too, and you get that 1.5, they're trying to get their transplant.

Timothy McClure: And they're not healthy to begin with, and in that situation if it comes back negative. You say, "Go ahead and clear the transplant." They get the transplant, they get healthy again, and then if you're still unsure, have them do the radical nephrectomy and the patient will do better from it. So I think it will be a real benefit from that perspective.

Zachary Klaassen: Yeah, love that point. I think that's great. The last two or three or four years, radioligand therapy has been just such a huge buzzword in prostate cancer and we're starting to see some other studies and other malignancies that we deal with. What are your thoughts on using this potentially as a theragnostic option as we go forward, 'cause certainly, there's probably some appetite for that, I would think.

Timothy McClure: Yeah, I think that's the future for a lot of these prostate cancer, kidney cancer, and I think, from a theragnostic perspective, I mean the door is wide open with regards to potential for this. I think we'll need a lot more well-designed prospective trials, good initial studies to show that you can potentially treat these tumors with theragnostics, and whether or not you do an intra-arterial, directed therapy or just standard IV, that remains to be seen. I think this will be useful though for those larger tumors where you're questioning, do you need to do a lymph node dissection, et cetera, I think that'll be helpful in guiding surgeons to do a thorough resection so we can get patients disease-free with that surgery from that perspective.

Zachary Klaassen: Yeah, great point. Tim, awesome conversation. Anything we haven't hit on that you want to touch on? Maybe a couple of wrap-up statements?

Timothy McClure: Yeah, I mean, I think the ZIRCON study is a great example of how imaging is improving, particularly with precision-targeted imaging to help better identify tumors. I think it's a great opportunity to work with our radiology colleagues to come up with new imaging strategies to help better identify patients who need treatment and ultimately lead to better management and less overtreatment of these small renal masses. Thanks again for having me. It was great being here. I appreciate it.

Zachary Klaassen: Oh, it was great to have you on UroToday. Absolutely. We'll have you back on. Appreciate your time and expertise and for educating our listeners.

Timothy McClure: Oh, sure. Have a good one. Take care everyone.