An interpretation of the OSPREY study of 18F-DCFPyL injection in patients with high-risk prostate cancer and implications of its use.
Alicia K. Morgans, MD, MPH: Let’s talk a little about the data that led to the 18-fluoride DCFPyL PSMA [prostate-specific membrane antigen] PET [positron emission tomography] agent. This was tested in several trials, both with bird-type names. Birds must have very good eyesight, perhaps that’s why. Scott, I’d love to hear you talk through this with us a little bit. The OSPREY trial was started a few years ago and was presented about a year ago in patients with high-risk prostate cancer, some maybe with locally recurrent metastatic disease. Can you tell us a little about the OSPREY trial and the 2 cohorts that were enrolled?
Scott T. Tagawa, MD, MS, FACP: Yes. Let me speak a little more broadly. Both of the FDA-approved tracers were tested in similar ways in terms of grouping patients, in terms of the label, suspected metastatic disease, or basically higher-risk disease prior to primary treatments. For both of the trials, their major readout in that situation was compared to histology and pathology. Then in post-primary treatment, biochemical relapse disease, there were additional data sets.
There are 3 different uses for PSMA PET that are essentially in prime time today. One is deciding on initial treatments, especially it’s helpful to know if there’s something we see outside the prostate or not. Whether that changes things, we don’t know, but it’s still useful information. With biochemical relapse, the major question is, where’s my PSA [prostate-specific antigen] coming from? When there’s surgery and then radiation, the PSA goes up. Localization can be quite helpful. And then, not that we have an approved agent yet, but it can be helpful in treatment selection, or at least optimization for metastatic disease with PSMA-targeted radionuclide therapy.
The 2 data sets, in terms of the preoperative settings, were almost identical. I agree with Phil that there are clear differences in radiochemistry. But for an end user, I don’t think they really matter. It’s probably not addressing the question today comparing both head to head—and there are several more coming—vs figuring out the best use for them and getting long-term data. That’s more important. But it showed basically the same thing, that when compared with the microscope, each one was only about 40%. But when we look at the larger results, in terms of true positivity, then we’re looking at 95% to 98%.
With OSPREY being published relatively recently in the Journal of Urology, and the Gallium-68 PSMA-11 from UCSF [University of California, San Francisco] and UCLA [University of California, Los Angeles] in press in the Journal of Clinical Oncology, we have to put things into perspective, in that the sensitivity of imaging is not going to be down to the single-cell level, like a microscope, especially with a microscope plus immunohistochemistry. But on a practical basis, it especially would expand this and go to something like proPSMA compared with CT and bone scan, then there’s really no comparison. CT, bone scan, and MRI led to some major advances, but not near the sensitivity of PSMA PET. It doesn’t approach the sensitivity of the microscope, but these are some major advances in prime time now.
Alicia K. Morgans, MD, MPH: I completely agree. Certainly, we’re not here to suggest that the Gallium agent is better or worse than the fluoride agent. From my perspective, any PSMA PET imaging that you can undergo is great, and there’s no evidence that either is better than the other. But it’s important to recognize and tell our patients that this will only identify PSMA-positive disease. That can be a challenge sometimes for patients who think, “Any of my disease should be identified.” But that’s not always the case, and we saw that in the TheraP trial. We’ll probably talk about that later. Some disease can sometimes be FDG [fluorodeoxyglucose]-avid, but not PSMA-avid, so it’s important to recognize this is only going to pick up the PSMA-positive disease. Phil, do you have any comments on that?
Phillip J. Koo, MD: That’s a great point. Something that we should re-emphasize is PSMA PET-CT is not perfect. As Scott mentioned, it doesn’t replace a microscope. For some reason, a lot of times I see PSMA PET equated to identifying micrometastatic disease, and that’s not true. It cannot identify micrometastatic disease. By definition, these are things that we’re detecting with microscope, pathology, and tissue. That’s important because it sheds light on the limitations of the imaging modality. Clearly, we’ve seen a lot of the trials that use PSMA PET to identify patients who will be treated and how they’ll be treated, like those oligometastases types of trials. What we see is those patients still recur. That’s because even though we might see 1, 2, or 3 lesions on a PSMA PET, in reality, there are maybe additional nodes that have micrometastatic disease that we’re not seeing with PSMA PET. It’s because we need a certain threshold of cells that are expressing the PSMA receptor in order to detect it on the PET-CT technology, on the hardware.
Alicia K. Morgans, MD, MPH: Great. Thank you for clarifying that. Although it’s a great way for us to identify low volumes of disease, it will not be able to replace a microscope.
Transcript edited for clarity.