Factors shaping PSMA-PET agent selection in prostate cancer

Clinicians ordering prostate-specific membrane antigen (PSMA)-PET can choose among several approved agents, including piflufolastat F 18 (Pylarify), flotufolastat F 18 (Posluma), and gallium Ga 68 gozetotide products.

In a conversation with Urology Times®, Chad R. Ritch, MD, MBA, FACS, who chairs the division of urology for the Cleveland Clinic Florida market, discussed how urologists weigh one PSMA-PET agent against another. He covered practical differences among the approved agents, how availability and scheduling shape ordering decisions, and which characteristics to consider when selecting agents in practice. He also shared his perspective on a head-to-head study of piflufolastat and flotufolastat¹ and the evidence needed to link imaging differences to patient outcomes.

Urology Times: What practical differences among the approved PSMA-PET agents should urologists understand?

Ritch: As far as practical differences, I think the newer agents relative to gallium have a slightly higher detection rate in the studies. What that means for overall outcomes and clinical management is still up for debate, because you can detect things, but it doesn’t necessarily mean that they’re actual true-positive findings, and it doesn’t mean that by detecting them, it’s going to necessarily change your overall survival. But the newer agents tend to have a higher detection rate than gallium.

Urology Times: How much does agent choice drive your ordering compared with availability, scheduling, and payer coverage?

Ritch: I think it really comes down to the region where you practice and even your own institution. Some institutions don’t have multiple agents, so you go with what’s there. I have not experienced any issues where the insurance or payer may cover one particular agent or not.

I do have cases where, with these agents in general, [it’s difficult] trying to schedule and get them, because they have to have the tracer prepared; it’s usually several weeks out. I may say to a patient, “Hey, I’m trying to get your surgery done quickly because you’re very high risk. We need to get a PET scan next week.” That may not be feasible in my hospital, which has all the agents, but it may be feasible at a facility outside, and I end up having to take whatever that facility is using. It really comes down to whatever is available, just to get a treatment decision made in a timely manner.

Urology Times: What characteristics should clinicians consider when evaluating one PSMA-PET agent against another?

Ritch: When you’re considering the different agents, [you’re] looking at detection rates; one may be higher than the other. The newer agents seem to be higher than gallium. You also want to think about things like false positives and uptake in areas close to where you’re interested in, so the prostate bed or the pelvic area. If you have a lot of uptake in that area naturally because of the agent getting filtered into the bladder, that can cause it to look somewhat positive vs others where you don’t have that situation. The newer agents, specifically Posluma [flotufolastat], don’t have that as much.

Urology Times: What should clinicians take from the multicenter study comparing piflufolastat and flotufolastat in low-PSA biochemical recurrence?

Ritch: With one agent, there appeared to be less uptake in the pelvic area and the bladder compared to the other, which helps you to get a more nuanced view of the prostate bed. If you’re trying to make a decision based on radiation therapy, and whether what you’re seeing is actually a true positive or just tracer uptake because it’s getting filtered into the bladder and creating that halo effect around that area, the newer agent may be better in that situation, specifically for the prostate bed.

There were some other findings in the comparison where they found better detection rates with one agent than the other. I think the bigger picture here is that those weren’t biopsy confirmed. You may pick up something more on the imaging, but if we don’t have histologic confirmation that what it was picking up more of was more cancer, then is it really better? Are we really helping?

The other question I had in that study was, did it change clinical management for any of these patients? The authors [weren’t] able to conclude whether or not detecting more suspicious areas in one group vs the other actually changed their management, or actually led to lower rates of recurrence or better metastasis-free survival.

With those types of comparisons, although it’s interesting and it makes you think that one agent potentially could be more helpful, unless you have the long-term clinical outcome correlation, you can’t say that I would rather use this agent vs the other without that clinical end point.

Urology Times: What evidence would show whether differences between imaging agents translate into meaningful outcome differences?

Ritch: The study that everybody would like to see is, if you’re comparing 2 agents head-to-head, [and] you have a higher detection rate with one agent, and that also aligns with your histopathologic confirmation, meaning you’ve detected it and you’ve confirmed it’s cancer, and that is better than the other agent, I think that is clinically meaningful.

The other thing in terms of outcomes is if one agent is able to detect more recurrence or metastases, and then you treat those patients based on that result, and their overall survival is better or prostate cancer–specific [survival] is better, then that is another clinically meaningful outcome. It’s great to have studies where you can see a difference in detection, or one agent showing it picking up more. But if at the end of the day it doesn’t improve the patient’s oncologic outcome, then detecting these things earlier or finding these things may not necessarily be clinically meaningful.

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REFERENCE

1. Nordquist LT, Andrews JR, Kuo PH, et al. An intra-patient contemporaneous comparison of 18F-piflufolastat and 18F-flotufolastat urinary radioactivity and pelvic region detection rates in men with low PSA biochemical recurrence of prostate cancer after radical prostatectomy. Eur J Nucl Med Mol Imaging. 2026;53(6):3529-3541. doi:10.1007/s00259-025-07732-y