Navigating the Complexities of PSMA PET in Prostate Cancer Management

In part of three of this prostate cancer roundtable series moderated by Jacob Ark, MD, the panel dives into the evolving role of PSMA PET imaging in prostate cancer management. Topics include nuances to consider when using PSMA PET imaging, differentiating false positives, and its implications on surgical, radiation, and systemic therapy decisions.

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Dr. Ark: So I think one of the biggest conundrum this goes to the point of talking about how do you pick this balance of quality and quantity for your patients.

Dr. Agarwal: Exactly.

Dr. Ark: And PSMA has only made that more complicated in my opinion.

Dr. Agarwal: Oh, yeah.

Dr. Ark: So I have some general scenarios that I’ll be curious as to how you guys manage it knowing that there’s no 100%. You talk to the patient, you get the history, you get a feel for what they want to do, what their pain points are or not, but with PSMA-PET having this increased detection rate, of course. Let’s start, Dr. Agarwal. If you got a guy, initial staging, conventional imaging would be negative. Let’s say it’s unfavorable, intermediate, high-risk, and it’s N1 on a PSMA-PET. What is your over 50% move in terms of managing that patient? Because all the 10-year studies are telling us, “That’s local, that’s local, that’s local.”

Dr. Agarwal: Yeah.

Dr. Ark: If it was N1 on conventional, NCCN say, “Hey, let’s do some systemic and some radiation.” How are you incorporating the unknown with trying to do what’s best for the patient?

Dr. Agarwal: Yeah. That’s a tough question. I think that each patient is individual, but a lot of times, the first thing I’ll do is review that image with the radiologist. Because many times, that N1, there’s no actual radiological correlate. It’s just positive.

Dr. Ark: Yep.

Dr. Agarwal: But when you look at the conventional CT that’s associated with the PET, there’s no actual lymph node that’s lighting up. The other thing is, in some PSMA-PETs, whether it’s F-18 or gallium, or… What am I missing there?

Dr. Bryan: Pylarify.

Dr. Agarwal: Pylarify, there’s little differences in nuances of where the uptake occurs. One is more sensitive for bone, one is less, one has more false positives. So I think understanding the nuances of the PET. But just to go back to the question, not trying to dodge it too much-

Dr. Ark: No, not at all because-

Dr. Agarwal: … but if you have a-

Dr. Ark: … [inaudible 00:13:13] bring my other question.

Dr. Agarwal: Yeah. But if you have a N-positive patient and there actually is a positive node there in the pelvis, if they’re a young patient, you have a little bit of a leeway now, right? Whereas before, if it was on conventional and you say, “Man, you’re not going to be cured,” but maybe there’s a leeway to say, “Hey, we don’t know if that’s actually a positive node. There is a false positive rate.”

Dr. Ark: Right.

Dr. Agarwal: Right? So we still proceed with maybe a prostatectomy, include the node in the field, and then we find for diagnostic purposes. You could also try to biopsy it with IR to say, “Hey, is this an accessible node to biopsy to prove, is this metastatic disease?”

Dr. Ark: Sure.

Dr. Agarwal: Because then there are implications, right? Prostatectomy has serious side effects for the patient’s quality of life. So, I think it’s nuanced. For me, I always try to figure out, is that node actually real or not? And that’ll exhaust that, whether that’s with the radiologist, with a biopsy. And if it’s still indeterminate, I’m going to give the benefit of the doubt probably to the patient, if they’re young enough and want to be aggressive, to consider a surgical removal of that lymph node with potentially their primary cancer.

Dr. Ark: And are there tracers in particular? You mentioned the most popular, that you would prefer to see-

Dr. Agarwal: We’re lucky we have the access to all of them. I think a gallium to me is the gold standard, gallium 68. We have Pylarify. It’s so easy-

Dr. Ark: It is.

Dr. Agarwal: … to order because it’s more accessible.

Dr. Ark: Right.

Dr. Agarwal: But luckily, we have a gallium scanner at our Mercy South location.

Dr. Finnie: Yeah.

Dr. Agarwal: So we can do that if you’re questioning something.

Dr. Ark: Yeah.

Dr. Agarwal: So it’s like I do think they’re all pretty good though. There’s not too much huge of a difference, except for when there’s a case of subtlety where you have to figure something out. But even a conventional PET, this is not-

Dr. Finnie: It’s not bad.

Dr. Agarwal: … terrible for a really aggressive for us.

Dr. Ark: Yeah. And so they talk about… What? 10% to 30%, depending on castration-resistant negativity on your PSMA-PETs. I’ll raise my hand, I’m not good about doing this part, but are you guys doing FDG-PETs, which is saying, “Hey, you know what? Let’s clarify. We really think there’s something there”? Are you guys utilizing that at all in the space?

Dr. Finnie: I’m mostly doing the Pylarify. I like to do that. If they seem symptomatic, I might CT and bone scan. But I think in general, I try to get that Pylarify if I can get it through the insurance. And the way things are changing, it’s the different imaging modalities. For breast now, we have PET Cerianna, which is very… I’ve done that on one person recently. We just got that at our center, and I saw two other patients today and I was like, “Hey, we can do this PET Cerianna.” You can’t do that one if they’re on a SERM, like tamoxifen or fulvestrant. But otherwise, you can. Sometimes, I think it’s important to know which drugs they are on so that you don’t wind up ordering the scan, and then you obfuscate it. You can’t interpret it. It’s like, “Oh, they shouldn’t have been on this.” So, that was an interesting learning point, I think, but it definitely is the sensitivity of these newer PET scans has been remarkable because we’ve seen it at conference. A lot more patients showing up with some oligo-bony metastatic disease that we didn’t suspect, and that changes your management.

Dr. Ark: And so, yeah, that’s where I want to go. I really hear you guys’ [inaudible 00:16:23] because I think this is the harder one. You have not N1, you have metastatic site, negative conventional imaging, and let’s say it’s an oligo. We talk about less than 4 on conventional imaging. There’s a number of criteria based on some different trials. Dr. Strope, let’s say you got a single bone met, de novo disease, and conventional looks reassuring.

Dr. Strope: Yeah, right.

Dr. Ark: What would you think is-

Dr. Strope: So, unfortunately, a bone biopsy is very low-yield, and so you don’t really have a great biopsy option there for you. So, your choices are to say, “I don’t believe it,” and then proceed with what you would have done anyway, which then, by all the data that we have, your standard of care, right?

Dr. Ark: Yes.

Dr. Strope: Because nothing that we have was based on finding oligometastatic disease on-

Dr. Ark: Correct.

Dr. Strope: … PET scan, or you could say, “Well, that might be real, so I’ll radiate it because there are data points for radiating oligometastatic disease, but it’s not in the guidelines,” and so you’re extrapolating beyond where guidelines are right now.

Dr. Ark: Yes.

Dr. Strope: I guess personally, I’ve gone not aggressively on prostatectomy in those cases because I’ve worried that I’d be too aggressive for that level of disease, and I’ve gone more towards the systemic therapy. That goes back to your point though, it’d be nice if we had some other really good biomarkers that we could use to help us with that to go, “Wait, this is suspicious, and I’ve got this other thing that tells-

Dr. Agarwal: Exactly.

Dr. Strope: … me that it’s really suspicious.”

Dr. Ark: Yep.

Dr. Strope: I think if you were following the guidelines and you had a unfavorable intermediate risk, you got a PET and you got that, and your PSA was 6, and the only thing that was unfavorable was your Gleason 7, then you might be like, “I don’t know.”

Dr. Ark: “I’m not sure I buy it.”

Dr. Agarwal: Yeah.

Dr. Strope: “I’m not sure I buy that.” I never even, in the old guidelines, would have gotten that scan at all.

Dr. Agarwal: No, no.

Dr. Ark: Right.

Dr. Agarwal: Yeah.

Dr. Strope: So that’s where it becomes really subtle. I recently had a guy whose only disease outside the pelvis was a ganglion that was lighting up on a PET.

Dr. Ark: And so that’s-

Dr. Agarwal: [inaudible 00:18:39] lighting, yeah.

Dr. Strope: And it was lighting up.

Dr. Agarwal: Oh, yeah.

Dr. Strope: There’s no CT correlate for it, so I’m like, “Do I not treat them? Do I call them broadly metastatic?”

Dr. Agarwal: Exactly.

Dr. Strope: So I’m [inaudible 00:18:48].

Dr. Ark: So I think that’s a good point of-

Dr. Agarwal: It’s a-

Dr. Ark: … false positives, especially on ganglion. So, parasympathetic gang… or sympathetic ganglion, absolute sympathetic chain is risk for false positivity, and people go and don’t know that, or, “This retroperitoneal lymphadenopathy.”

Dr. Agarwal: Oh, no. It’s exactly, yeah, yeah.

Dr. Ark: And yeah, you have to be very careful because these makes false positives.

Dr. Strope: So the funny is he actually had GI symptoms though and it’s like, “Is that related?” And so when I started his ADT, I’m like, “Are your GI symptoms better?” He’s like, “Yeah.” I’m like, “Ooh. So was that real?” “I don’t know.”

Dr. Ark: There’s report of macrophage having PSMA expressivity. Have you guys noticed this in inflammatory stuff, like false positives at all in those PSMAs?

Dr. Finnie: You know what? Lately, it seems like I’ve gotten a couple of lung nodules, and that’s where I end up getting an FDG-PET.

Dr. Ark: Okay. Yes.

Dr. Bryan: Back to that. But I had a lady the other day… or I’m sorry, a guy the other day whose thyroid lit up, and we did an ultrasound. He had a thyroid tumor. That’s not listed in the cross-reactivity, but-

Dr. Ark: Right. Interesting. Yeah. Yeah, I think knowing when to chase it and when to not is a good skillset. So I think we’ve covered a good bit on some of the role of radiation in these spaces.

Dr. Agarwal: Oh, one thing I was going to say-

Dr. Ark: Please.

Dr. Agarwal: … the CLL, well, you got to be careful on that, too, because we’ll see people who have this smoldering CLL. They’re of that age where you could get both prostate cancer and that, and so that’s where they may say node-positive. That’s where maybe a biopsy or peripheral smear somewhere, or-

Dr. Finnie: [inaudible 00:20:19] adenopathy and it’s a CLL.

Dr. Strope: Right.

Dr. Ark: Yeah.

Dr. Agarwal: Exactly. And they’ll light up on those PETs, or PSMAs even.

Dr. Ark: So, Dr. Finnie, I’m curious for your input on this one because we talked about what the heck do we do with radiation surgery for these PSMA differences. When you’re seeing classically unchartered, stampede, high-volume disease on a PSMA-PET but not necessarily meaning conventional, how are you managing those patients in terms of chemotherapy?

Dr. Finnie: No, I’d look at… individualize it, see, “Okay, how old are they?” the PSA velocity, look at all those features. And we’ve reviewed a lot of those patients at conference. And typically, the med-oncs will speak up and say, “Do they have four or more lesions? How many?” But I think it’s a great point, too, getting back to the Taxotere data, docetaxel is almost… When you look at those trials, that show maybe it’s a 16-month improvement in their overall survival, which was very surprising. When they designed those trials, they said, “Oh, we got the signal.” I don’t think they were expecting that, but that’s in the pre-darolutamide, pre-enzalutamide era. It’s before-

Dr. Bryan: 2004.

Dr. Finnie: Yeah.

Dr. Bryan: Yeah.

Dr. Finnie: It’s before we had such effective systemic therapy. So it makes you wonder, are they going to be able to compare in this modern era?

Dr. Ark: Yeah.

Dr. Finnie: So that makes it difficult. And another point I would get at is we’ve had mutual patients. Some person is getting docetaxel, and we’ll never forget the guy.

Dr. Agarwal: Oh, yeah, yeah.

Dr. Finnie: His brother was a famous AML researcher. Dr. Agarwal said, “You’re done. You’ve had four cycles. Dr. Finnie is not going to give you five and say… because appropriately.

Dr. Agarwal:  Tears him up a little.

Dr. Finnie: Appropriate because this poor guy was just-

Dr. Agarwal: He’s strong, he’s strong.

Dr. Finnie: You have to look at the… Docetaxel has asthenia. Especially 75 milligram per meter squared, it’s a tough.

Dr. Ark: It’s a tough drug.

Dr. Finnie: And if you’re trying to translate to give them that, it’s like the paradigm of head-neck chemoradiation. You put them through this unbelievably horrific thing to give them a cure for decades.

Dr. Ark: Yeah.

Dr. Finnie: And docetaxel, you select the right patient and make sure they know what they’re getting into. And it does have a big magnitude of benefit, but it’s still something to think about.