Patient Scenario 1: nmCRPC Identification and Work-up

Centering the discussion around a patient with nonmetastatic castration-resistant prostate cancer, experts share insight on optimal work-up and testing.

Robert Dreicer, MD, MS, MACP, FASCO
: We’re going to move into trying to talk more about the disease state that historically we’ve evolved to calling nonmetastatic castration resistant. Let’s do a little background before I present the case. To get to nonmetastatic castration resistant, you had to be started on testosterone suppression. By definition, you didn’t have metastatic disease. This is an interesting disease state because in a sense it’s somewhat of an artificial construct. It could come from patients who were treated with radiation therapy for locally advanced disease and were maintained for 2 to 3 years as per prospective level 1 evidence, but then developed biochemical progression in the castrate setting. Many patients may have been started on ADT [androgen deprivation therapy] for PSA [prostate-specific antigen]-only disease. It’s in that setting that there’s still a fair amount of controversy since we don’t have level 1 evidence to support that yet. We may at some point. We don’t, but either way, however you get there: nonmetastatic castration resistant, rising PSA, no evidence on conventional imaging, bone scan, CT scans. We’re going to come back to talk about that more. That’s the disease state.

Let me present a case to my colleagues for their input. This is a 62-year-old gentleman who presents, now he’s 2 years out from a robotic prostatectomy. He had a Gleason score of 4+5, grade group 5. He had a detectable PSA following his prostatectomy. He received salvage radiation therapy with a 6-month course of testosterone suppression. He’s now in your office, he has a PSA of 7.6 [ng/mL], his PSA doubling time using the last 3 values was 8.8 [months]. His testosterone is 33 [ng/dL]. He underwent recent conventional imaging. His bone scan was reported as being without evidence of metastasis. On CT of the abdomen and pelvis, there appear to be 2 pelvic nodes, one 1.4 cm and the other 1.2 cm, picked up by your radiologist. His ECOG performance status is 0, and he is understandably anxious about what’s next. Dr George, do you see these kind of patients? Is this a real-life kind of patient, or is this bizarre?

Saby George, MD, FACP: I do see these patients, not quite often because a lot of patients who present with biochemical recurrence are originally seen by the urology side. They are referred to us when they present like this or become castration resistant, technically nonmetastatic. If the lymph nodes are 2 cm… if it’s short axis, it is measurable disease, and it could be considered metastatic for radiographic assessment. If it’s in the short axis and it is less than 1.5 cm, then it could be nonmetastatic. If it’s a bigger one, it’s metastatic; if it’s the second one, it is nonmetastatic.

Robert Dreicer, MD, MS, MACP, FASCO: This is going to lead into the conversation we’re going to have about this. This goes back to the issue about the use of ADT in the nonmetastatic setting to begin with. Historically the field—the folks, people of our ilk, our colleagues in the community, our urology colleagues, radiation oncology—everybody who has intervened with T-cell suppression for rising PSA, presumably does it because they believe that there’s micrometastatic disease. We all understand this. The 2-cm thing, Saby, you would agree this is an arbitrary construct. If you’ve got 1.8-cm nodes, and I didn’t stick a needle in it for you to tell you what it was, you presume it’s a disease. This is just a volume thing. We say this because we’re going to talk about the 3 large randomized trials that led to the regulatory approval of 3 androgen receptor inhibitors, darolutamide, enzalutamide, apalutamide, and a couple of other trials that defined 2 cm or less. Although one could argue, could it have been 2.2 cm or 1.8 cm? This is an arbitrary construct. What we’re really talking about is using therapies early in the metastatic setting. I know you both see patients like this, and we’re going to come back to the interdisciplinary issue, which you raised, because it’s an interesting construct in the disease that we take care of.

Let me shuffle a bit before we get into the trials in more detail and ask Dr Scholz, you have a sophisticated practice. You’ve been using next-generation imaging for a considerable period of time, and more regularly, perhaps, after the fall of last year when the fluoride agent became regulatorily available to us. This phenotype of patient today, let’s put aside, because we all live in different parts of the country, we all have different payers, and this is not a Medicare patient, so we all might have challenges. But if you had your druthers and you had access to whatever test you thought was appropriate, this patient, he comes to you with conventional imaging, and he comes to you with what I’ve shown you, but now he’s your patient. He says “I need you to take care of me.” Does this patient get a PSMA PET [prostate-specific membrane antigen positron emission tomography]?

Mark Scholz, MD: Yes. You’re right, sometimes insurance coverage for the non-Medicare group is challenging, but there’s a facility in Northern California that will perform these tests for affordable rates. We’re ordering 5 or 6 PSMA PET scans daily out of the office. I think that if we have, and we do have access to these PSMA PET scans now, that CT and bone scans are an antiquated methodology. Where this leads is the potential advantages of multimodality therapy, trying to go after oligometastatic disease. But with a better scan, if you see a limited number of METs [metastases], which hopefully you will, then the possibility of a meaningful benefit from radiating metastatic lesions, using multimodality systemic therapy, is more likely to have a big payoff.

Transcript edited for clarity.

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