Oliver Sartor: Well, glad to be here. We've got a lot of topic to cover here on PSMA PET. It's a big topic.
Phillip Koo: It is a huge topic. Very exciting. So, now that we have it approved in that CRPC space pre and post-chemo, what's your approach to PSMA PET imaging when patients become castration-resistant?
Oliver Sartor: I like to be able to get the scan done relatively early, not late. So, when the PSA starts going up, one, two, three, I'm thinking about where the disease is. Is it oligometastatic disease? Can I use SBRT? Do I even need systemic therapy?
Sometimes honestly what we find, Phil, we find two little vertebral lesions, just goes zap, zap with SBRT, and nothing else is there. The PSA will fall down and then you just continue this plan. So, not everybody that has a PSA recurrence in castrate-resistant is going to really convert over into the nasty CRPC disease that we often treat and talk about.
Phillip Koo: All right. So, there are some nuances in which case you might do external beam radiation for some of them. That's in certain situations. So, then in what clinical scenario would you lean towards going towards Lutetium-177 PSMA?
Oliver Sartor: There are a couple of factors that kind of push me. Number one is I'm going to be looking at polymetastatic versus oligometastatic. So, if somebody has two or three lesions, it's different to me than if they have seven to nine lesions. So, some patients are better for systemic therapies, some patients are more appropriate for local therapies. That's one distinguishing element of mine.
I'm also looking at the degree of progression. Are these patients whose PSA is kind of going 0.1, 0.2, 0.3? Or is this more of a PSA 10, 20, 45? The degree of systemic disease in terms of the intervention is for the patients who have that more galloping, more rapid development of the disease, and I like to know where it is and then put together a plan.
Phillip Koo: All right. So, you're really relying... I guess understanding the biology and whatnot. So, if you do lean towards systemic therapy, how are you making that decision to choose a radioligand therapy versus, let's say chemotherapy?
Oliver Sartor: Great question, and let me say that we struggle on this question. There was a trial that came out of the ESMO 2025 called the PLUTO trial, that's Pluvicto, docetaxel, and they did a head-to-head comparison between the Pluvicto and the docetaxel. And actually the docetaxel looks really good.
These are patients who are more chemotherapy-eligible. Visceral disease, liver metastasis, higher-volume disease, more progressive disease. I talked to Kim Chi about it, who gave the presentation. He said, "These are patients that need to undergo chemotherapy." These are not patients who are kind of rolling along with a little PSA rise. These are patients who are galloping and they need an intervention.
So, there's a bit of art form here, and I'm not sure that I can completely classify chemo versus the Pluvicto patient, but let's put it this way... More PSMA PET positivity, I like Pluvicto. More liver disease, I'm thinking about more chemo. If the patient's PSA is relatively low and a little more tame, going up with a doubling time of, say six months, I'm thinking more Pluvicto. If their PSA doubling time is really more in the one to two-month, I'm thinking more chemo.
So, these are not perfect guidelines, because we don't have the perfect guidelines. And I'm simply going to say that both treatments may be optimal. And please remember, we had the VISION trial and we have the PSMAfore trial, and one was before chemo, one was after chemo, and it worked for both.
Phillip Koo: I think that's a really great point, and again, it seems to go back to the biology. It seems like PLUTO is probably a little bit of different patient population compared to PSMAfore. Is that...
Oliver Sartor: I think so.
Phillip Koo: All right. So, let's say you make a decision to go ahead with, you order the PSMA PET-CT, you get the results back. How are you interpreting the impression that you see on the report with regards to the decision-making for Pluvicto versus another treatment?
Oliver Sartor: I'm kind of looking at the reports on myself and then the scans themselves. So, I want to look at how much PSMA SUVmean there is. Is this a patient with lots of SUV uptake in their lesions? They have seven lesions, all hot, hot, hot? Or is this a patient who's got three hot lesions here and another lesion down on the hip, and it's like, "Ooh, that's not even hot at all"?
And the heterogeneity is a bad sign for the Pluvicto-treated patients. You want uniformly high. So, polymetastatic disease, uniformly high PSMA uptake, that's a good patient to think about Pluvicto.
Phillip Koo: I think this is a real good teaching point for any of the imaging people out there, that in your reports you should probably specify number of lesions, location, and in general give an indication with regards to how much of the radiotracer the tumors are sort of taking up. Is that summarizing...
Oliver Sartor: I think that'd be great. I'm trying to intuit that off my own reading, but if I could get somebody to tell me how many lesions are present, what's the SUV, what's the SUVmax, SUVmean, and feasible... How much heterogeneity there is. Location. Is it liver? Is it bone? Is it lymph node? By the way, the lymph nodes do very well and the liver does very bad. I call it the "hierarchy of badness". So, liver's bad, lymph node's good.
And we're also looking at the patient and their symptoms. Are they doing fine? Are they managing taking a little Tylenol here and there and managing their pain? Are they starting to gobble some Percocet along the way because they're really starting to have pain?
So, there's a variety of parameters that we look at, but thank goodness we typically do have options for these patients. We can treat them with more than one therapy. We have the docetaxel. We might even have an RP switch. We might even have SBRT alone. We might even have some sort of BAT-type therapy with high-dose testosterone.
So, we're not locked in. And of course I should also mention the PARP inhibitors and the PD-1 inhibitors for those who might have particularly selective molecular defects.
Phillip Koo: I think it's good to always think about that. So, let's say the patient is started on Pluvicto. How are you following them with PSMA PET once they start treatment?
Oliver Sartor: Good question. So, clinical parameters. Pain and how do you feel of course are very important. I'm looking at the PSA and I'm typically following the PSA at least every six weeks, maybe even more closely. I'm watching the alkaline phosphatase and the LDH just because I'm kind of keeping track. And I'm also watching the hematologic parameters, because some of these patients begin to have more mild suppression than you would suspect. I use scans if I start feeling uncertain. Like if the patient is beginning to progress, I'll drop in a PSMA PET scan if I can get it.
The problem is we often have trouble on the PSMA PETs because they've already had a recent PSMA PET at the baseline of therapy and now the insurance company doesn't want to pay for another. So, we do run into some problems with repeat PET. We can use SPECT as well, but our team is not as experienced in SPECT. I'd like to get better at SPECT and we're going to get better in SPECT, but not really yet.
Phillip Koo: All right. So, let's say the patient starts down the docetaxel route. At what point would you re-image them with the PSMA PET?
Oliver Sartor: Again, based on the clinical parameters, the patient's got a PSA decline, LDH decline, pain relief, I'm pretty okay just to wait a little bit. For the patient who's starting to have a PSA increase, starting to have a pain increase, I want to start scanning that patient and taking a look, and sometimes you get nasty surprises. It's imperfect. The problem is what I'd like to do is to give the PSMA PETs every six to twelve weeks, but the insurance companies don't let me do that.
Phillip Koo: So, it sounds like the PSMA PET obviously is such an important tool. It's really transformed how we practice, and it's really important it sounds like to get it early and that it informs a lot of our treatment downstream.
Oliver Sartor: I really like to look at it because it makes me understand the patient's disease and biology a little bit better, helps me understand the response to therapy better. And as we go forward, I think we're going to have better reports and better outcomes because we now know how to manage these patients in a little more sophisticated way.
Phillip Koo: Well, I think these are wonderful points. I think it helps clarify how we make our decision-making and I think it clarifies how that PSMA PET informs that. So, I really appreciate the time and the education on this topic.
Oliver Sartor: Well, thanks, Phil. I appreciate being here.