Metastatic CRPC: Utility of Imaging as a Biomarker

Transcript:
Alicia Morgans, MD, MPH: Let’s shift gears a little because there has been, as we discussed in other modules, advances in imaging and the use of imaging as a biomarker in other situations. I think in the metastatic CRPC [castration-resistant prostate cancer] setting, imaging can also be a very important biomarker. The thought is that this is what we might consider a phenotypic biomarker to use imaging in this setting. I wonder, Scott, from your perspective, what do you think is the role of phenotypic biomarkers in selecting patients for treatment, whether it’s immediately or in the near future as therapies are newly available to us? How useful is this?

Scott T. Tagawa, MD, MS, FACP: I think it’s very useful. I think that we, without realizing it, have used imaging as biomarkers, at least prognostic, for forever. So, node only versus node plus bone versus visceral, particularly liver, we’ve known about in terms of prognostic biomarkers for a long time. Those in combination with other biomarkers can be phenotypic. For instance, a bulky pelvic metastasis and liver [metastases] with a low PSA [prostate-specific antigen] have been ways of looking at different phenotypes. There’s also some terminology that I am not going to get into, but different types that might respond better to certain drugs or not as well to other drugs, but regardless of what we use, these are at least prognostic in terms of survival. We’ve been using those for a long time.

We transitioned into molecular imaging, in a way, a long time ago. We’ve had different types of PET [positron emission tomography] imaging. We’ve had PSMA [prostate-specific membrane antigen] imaging for decades. People forget about the first PSMA imaging agent, which is a couple of decades old, the antibody didn’t work well. I’m not going to spend a long time on that. We’ve known for instance FDG [fluorodeoxyglucose] PET imaging has been prognostic. We’ve known that for a number of years from MSK [Memorial Sloan Kettering Cancer Center] data and others. There are other targets, such as DHT [dihydrotestosterone], in terms of imaging, are we hitting the AR [androgen receptor] pathway, at least in the setting of castration?

Then PSMA imaging is not so new when we look at it worldwide, but it is very new in the clinic, at least in the United States. We have a number of different opportunities there at different disease states: walking in the door, localization, where is it, head-to-head comparisons with CT and bone scans. I think the proPSMA study was mentioned earlier today. At least in the Australian data set, not only is PSMA PET better in terms of sensitivity and specificity, but it’s also cost effective. It may not be true in the United States. But based on what they charge for PSMA PET, it was superior as well as cost effective.

I mentioned prognostic data with a number of these different imaging agents. It looks like it is also predictive, at least in certain situations. We now have from ASCO GU [American Society of Clinical Oncology Genitourinary Cancers Symposium] 2022 imaging data looking at both predictive and prognostic imaging data from the TheraP study. These were highly selected patients by PSMA and FDG imaging to get in. But once you’re in, you’re randomized to 177Lu-PSMA-617 [lutetium PSMA] versus cabazitaxel. Validated in that data set was FDG as a prognostic biomarker, but also given the randomized nature of the study, was a predictive biomarker. Among those who had to have bright [standard uptake value (SUV)max≥20] imaging by PSMA PET to get in, those with the brightest imaging did even better with lutetium PSMA. There was no difference with docetaxel as a predictive biomarker. That’s just the tip of the iceberg. I think with additional study, we’ll be able to use a lot of these different tools to examine all different sites of disease at the same time. That’s an advantage of an imaging tool where certain areas might be brighter than others, or if we have more than one imaging type, where certain areas will lighten up and other areas won’t with certain tracers and vice versa.

Alicia Morgans, MD, MPH: Thank you. That’s really helpful and leads right to my next question, which I have for Matthew. When I think about the use of phenotypic biomarkers, of course Scott mentioned several different PET imaging strategies, such as PSMA versus FDG, what do you think of the use of these phenotypic biomarkers in terms of characterizing what can be pretty significant disease heterogeneity in patients with metastatic CRPC? How useful, in that context, will that be, the use of these different imaging strategies? Is this actually going to be feasible in our clinical practices?

Matthew R. Smith, MD, PhD: I think it is. I believe that, based on comments from my colleagues, PSMA PET is really going to transform the field. There’s going to be a tremendous stage migration by identifying patients who previously were thought to be nonmetastatic being classified as metastatic, but also identifying additional sites of disease in patients with known metastases. It’s going to be extremely informative in making decisions about timing of therapy and selection of therapy. Probably the best example is the one you just heard. PSMA lutetium is going to be appropriate for patients whose tumors express PSMA and not for the small minority who don’t. That is the ultimate in biomarkers. There are other drugs that we consider. For example, radium-223 is really only appropriate for patients with bone-only or bone-dominant forms of the disease. I don’t know that we’ll need to go backward too much. But maybe before you make the decision about giving radium-223, you probably would be obligated to do a technetium bone scan, but I don’t think you’re going to be doing those tests concurrently. You’ll be doing it when it’s going to change the decision-making for an individual patient.

Alicia Morgans, MD, MPH: That makes complete sense. Thank you for walking us through that.

Transcript edited for clarity.