Practical Advice on Novel Imaging Strategies in Nonmetastatic CRPC

Expert perspectives on optimal patient follow-up, with particular regard for PSMA imaging, in nonmetastatic castration-resistant prostate cancer.


Eleni Efstathiou, MD, PhD: This is the case description with regard to the PSAs [prostate-specific antigens]. The patient was obviously following his PSA [level]. When he started on leuprolide in October 2019, it was 1.1 ng/mL. By January 2020, the PSA started to go up, at 1.5 ng/mL. By March, 1.8 ng/mL. By June it had doubled from October, to 2.3 ng/mL. By May 2021, it had doubled again, to 4.1 ng/mL. You can see early on with this gentleman that he had an early castration-resistant [reaction]. He’s primarily refractory to androgen signal inhibition in the form of ADT [androgen deprivation therapy]. He had re-presented himself to the clinic in October 2019. The PSA doubling line more formally calculated is 8 months. Conventional imaging at the time was negative for metastatic disease. Performance status was 0.

Alan Bryce, MD: Let’s ask this question, though, because we started to touch on this concerning imaging. This patient had his CT scan and bone scan, but what about advanced imaging in this situation? Eleni, what would you expect to see from advanced imaging?

Eleni Efstathiou, MD, PhD: There is a lot of controversy here. One opportunity is to offer it up front, to have a knowledge of how extensive the disease is. But how will it affect your decisions, especially in younger men? I would hate for it us to backtrack and stop treating the primary, for instance. If you were to offer it upon the time of relapse after your radical prostatectomy, maybe you would have gained more knowledge, especially with PSMA [prostate-specific membrane antigen], whether or not you’re going with any tracers available to us. That would have given you the opportunity to understand if you’re looking at oligometastatic bone disease or just nodal disease.

At the moment that the disease is castration resistant, I believe we’d get a lot of resistance, a lot of kickback, from physicians saying, “At this time, what are you going to do?” You’re already looking at disease that is CRPC [castration-resistant prostate cancer]. In my practice, I’d argue that having the information or whether you’re looking at distant metastases that are only locoregional in the pelvis when you haven’t irradiated may also have a role. There’s no such thing as too much information. There is such a thing as overreaction based on information, which is a completely different story.

Alan Bryce, MD: Fair enough. Dan, your thoughts on the imaging?

Daniel Landau, MD: It’s a great question. We offer PSMA testing at our site. This is very rapidly becoming our go-to imaging modality, especially for patients who may have high-risk disease. I’m seeing that either a number of my community partners don’t know that we have PSMA or don’t have easy access to order PSMA testing. It appears that the more traditional bone scan, the CT scan, is still the most commonly used test, but I hope that we’ll have a day when PSMA overtakes them because it tells us much more information.

Alan Bryce, MD: One thing I’d like to point out to our listeners is we do have some retrospective data. We’re going to hear about some of the nmCRPC [nonmetastatic CRPC] studies, but the leading nuclear medicine groups—including the UCSF [University of California, San Francisco] and UCLA [University of California, Los Angeles] groups and the Australian group [Australian Prostate Cancer Research Centre]—have done a retrospective study that looked at men who qualified for the 3 nonmetastatic CRPC studies. [They had] rising PSA, a doubling time of 10 months or faster. By conventional imaging, nothing more than pelvic nodes of 2 cm. They looked at men who qualified by those criteria and asked, “What did their PSMA stand show?” In the retrospective analysis, 98% of patients had a metastatic lesion by advanced imaging. It’s everybody—the answer is everybody.

The point that I’d make is to remember that the PSMA scan is not changing the biology of the tumor. Nonmetastatic patients have metastatic disease. They always have. We know that. It’s just micrometastatic. It’s too small to see by conventional imaging. When advanced imaging shows us these extra lesions, if indeed you get it, that shouldn’t be cause for alarm and overreaction, because it doesn’t change what’s going on biologically. It just gives us more specific information about where these metastases are located.

You’ll see these scans come into your practice over time. There’s always a phased adoption across the country. It will be the subject of many Targeted Oncology™ recordings as we discuss how we handle those data.

Daniel Landau, MD: I’ll offer this a bit tongue in cheek, but how many times have you ordered a bone scan on a patient and the read comes back entirely confused—possibly the disease is better, possibly the disease is worse—and you can’t tell the difference? With PSMA, [there is] much more clarity.

Eleni Efstathiou, MD, PhD: Absolutely. Your point is very strong, Alan, in the sense that we shouldn’t drive ourselves nuts. Because I gave that presentation at the Consensus meeting [Advanced Prostate Cancer Consensus Conference], I scratched out “nonmetastatic” and wrote “early CRPC.” Let’s call it that. It’s not perfect. It’s better. It’s like what we used to call L1. It’s early CRPC that we can visualize better and get more information because everyone went crazy. What are we going to do with the data we’re going to talk about in a minute? Nothing, because the data are the data. All you need to do is remove from your imaging the PET [positron emission test] part and look at that CT scan. Are you seeing anything? No, you’re not. Done—it’s very simple.

Transcript edited for clarity.

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