Optimizing Use of PSMA PET Imaging and PSADT in Prostate Cancer


Shared insight on the respective roles of PSMA-PET imaging and PSA doubling time in the current prostate cancer treatment paradigm.


Alicia Morgans, MD, MPH: Scott [Scott T. Tagawa, MD, MS, FACP], when you think about that, what are your thoughts in terms of the pros and the cons? The things that we appreciate, but the things that we also might need to be cautious about?

Scott T. Tagawa, MD, MS, FACP: With any new technology or treatment, in my opinion, it's great to have more options for our patients, but sometimes they significantly will change the landscape. I think that's true of PSMA [prostate-specific membrane antigen] PET [positron emission tomography]. As Evan [Evan Y. Yu, MD] mentioned, I think there's no question, particularly, let's say, in the biochemical relapse setting, if we can localize at least confined to the pelvis, ie, amenable to local salvage therapy, that might lead to cure or not. I think that helps us. Before we were a little bit shooting blind, at least when it came to radiation, although I will make the comment that any time a patient, let's say, has surgery, PSA [prostate-specific antigen] is up, and I am ordering a PSMA PET. I was telling that patient and his family, “I hope that we see nothing” because that generally leads to the lowest burden of disease. Those men probably have the highest chance of a cure with solid radiation.

Anyway, getting back to your question about what other questions do we have. Some of the time we see patients that have either high-risk or intermediate-risk localized disease or have a biochemical recurrence that we think then we see metastatic disease on PSMA PET, that we may not have seen on conventional imaging. We have a lot of data that we'll talk about in terms of therapeutic advantages with multiple drugs in that non-gastric metastatic disease setting, but that's for conventional imaging. So, if you see something on PET only, but not in conventional imaging, what does that mean? It's led to an extrapolation of data. Sometimes I will go back and get a bone scan after that, in the setting of what has been termed M0 CRPC [castration-resistant prostate cancer], or nonmetastatic CRPC, but I believe we're also going to talk about some therapy advances. Nonmetastatic was based on CT, MRI, and bone scan, and we know that the majority of the time, particularly in higher-risk groups that were enrolled in the clinical trials, with a shorter doubling time, we almost always see something, whether it's only in the pelvis or outside is a little bit different. These drugs probably work whether we can see them or not. Then 1 additional item that I think is an opportunity is that we have very clearly been able to look for metastatic disease, metastatic CRPC, and more specifically, we’ve been able to follow progression radiographically in everyone, and that’s led to some of the drug approvals, radiographic progression-free survival, but only a minority were eligible to see a radiographic response, because in bone scans, we can't really see response, only progression. I think that we might be able to see this with molecular imaging, whether it's PSMA PET or others, depending on the specific situation. I think that leads to opportunities to be able to do that. But my goal is not to make a PSMA PET better unless that's clearly associated with other outcomes like survival. At this point, that is something that I'm very interested in investigating but not something that I'm clinically using right now.

Alicia Morgans, MD, MPH: Those are all such great points. I appreciate that, Scott, and I also just want to emphasize 1 of your first points, which is that having a negative PSMA PET is actually a great thing in biochemical recurrence because we still do, I think in most cases, want to do the standard of care, which would be radiating the pelvis in a postprostatectomy patient who now has biochemical recurrence. We might add something on if we see something on a PSMA PET, but the less disease that we can see, the less disease hopefully there is. That's a good thing. Thank you for that. I think your other point about how making the PSMA PET better is not necessarily our goal. Our goal is to help the patient live longer and feel better or improve an outcome. Whatever that outcome may be is also important. As we think about the other things that we follow for our patients in the biochemical recurrence space, there are other things that we think about, including things like PSA doubling time. Matthew [Matthew R. Smith, MD, PhD], I'm wondering from your perspective, are you still using PSA doubling time? How does that come into your decision-making practice when you're thinking about the biochemical recurrent state in particular?

Matthew R. Smith, MD, PhD: Sure. It's unavoidable, right? We have a lot of PSA data on our patients, and a faster rate of PSA rise or shorter PSA doubling time has been consistently linked to worse clinical outcomes, including shorter time to metastasis, and in the CRPC setting, shorter overall survival. It's there to stay. I think it'll help. It'll continue to inform other decisions, including about the timing of imaging, whether it be conventional or PSMA PET imaging. There are very nice data from the registration studies for the PSMA PET imaging agents that a higher PSA is associated with a higher rate of positivity, to no surprise. I don't know that they have the same data for PSA doubling time, but I would speculate that the same would be true, meaning that a shorter PSA doubling times is likely to be linked to a higher rate of PSMA PET positivity. So, I think PSA kinetics are going to remain an integral part of decision making, particularly for patients with biochemical recurrence.

Transcript edited for clarity.

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