PSMA PET Scan Imaging in Prostate Cancer - Ashley Ross
November 4, 2022
Ashley Ross, MD, Ph.D., Associate Professor, Department of Urology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois
Alicia Morgans, MD, MPH, Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts
NCCN Guidelines Update on Selection of PSMA PET Imaging Agent in Patient Selection for Lutetium-177-PSMA-617 – Oliver Sartor
ASCO GU 2022: Targeting Prostate-Specific Membrane Antigen: Lutetium and the Next Wave of Novel Radiopharmaceuticals
Alicia Morgans: Hi, I'm so excited to be at ASCO 2022, where I have the opportunity to speak with Dr. Ashley Ross of Northwestern University about imaging with PSMA PET scans in the metastatic CRPC space and how the recommendations and guidance have evolved in the NCCN guidelines as we think about using things like lutetium in our clinical practices. Thank you so much for being here.
Ashley Ross: Thanks for having me. Always a pleasure.
Alicia Morgans: Wonderful. Well, I love speaking with you because I think that your guidance is so very useful in clinic. I'd love to hear your thoughts about how we think about PSMA PET scans and identifying patients who are going to be PSMA-positive and potentially eligible for treatment with lutetium in the metastatic CRPC setting. This is something that I think has gotten a lot of attention because the label for lutetium suggests that we really need to use a gallium PSMA PET scan to identify patients, and the NCCN guidelines differ a little bit. Can you tell us a little bit about that?
Ashley Ross: Yes, for sure. Again, thanks for having me. I always appreciate being here. PET imaging really has come into its own in prostate cancer and really come fast. Now there's actually multiple different agents. When we think about imaging for prostate cancer, particularly PET PSMA targeted imaging, a lot of that grew out of work by Marty Pomper and others way back at Hopkins. It was recognition that a urea molecule will sit in the active site of the PSMA and by that virtue you could then label it with F-18 or gallium and it could home into prostate cancer, particularly on the extracellular domain of the PSMA molecule.
A lot of tracers came out. If we look at the FDA approvals for imaging for prostate cancer, back in 2000 and 2021, we saw approval of the gallium PSMA-11, and then the DCPyL compound, which was the F-18. Then even more recently, there's been a couple other gallium compounds that have come to market, and all of these are structurally similar. There are very minor differences. Obviously, gallium and F-18 have some differences, but they're structurally similar, they have very similar performance characteristics. This would be very different from comparing apples to oranges, which would be PET PSMA to something like fluciclovine, which is looking at an amino acid transporter, a completely different molecule, lutetium-based. They both have prostate cancer specificity, but those are apples and oranges. A gallium PSMA-11 compound versus a Pyl compound, in my opinion, at least is sort of looking at an Envy apple versus a honey crisp apple. These are apples to apples.
That's what the NCCN said too. Oftentimes in trials, tests are developed with a companion diagnostic, and there's some things that people are more used to and less used to. So when the VISION trial reported, as you mentioned, they were using the gallium PSMA tracer. Because they were using that as their companion diagnostic, the FDA said, "Look, this was the companion diagnostic, is patients that have metastatic CRPC, they've had some type of androgen-directed therapy like abi, for example, and they've had docetaxel and they're showing PET positivity by the gallium tracer, and they don't have dominant PET negative lesions, these are good candidates for lutetium and that can increase their overall survival and increase their progression-free survival.
Then the question was, well, does that make practical sense? A lot of us had already onboarded F-18 DCPyL, or Pylarify, in our practices. There's the distribution of that through PETNET was much, at least for me in my practice, much more solid. There could be supply line problems with gallium, or maybe in your area gallium's easier to activate or maybe a different gallium tracer because there's actually multiple on the market. Are these things functionally equivalent? What the NCCN said is based on what I sort of talked about before, which is they're structurally similar molecules with structurally similar binding sites. The evidence behind them, although there haven't been a lot of direct head-to-heads that are large, suggests that they're recognizing the same moiety, recognizing the same disease. We should use them as equivalent in patients that have F-18 PyL PET-positive with Pylarify or with the other gallium tracers that are mCRPC, have gone through docetaxel and these other AR inhibitors, show lesions that are PET-positive, these should be lutetium candidates. I strongly endorse that.
I think that was good because this is an implementation issue. The drug works. How do we get it to the patients? Is this functionally equivalent? Yes. What I thought about in my mind when there was a little bit of back and forth and buzz about this, should our institutions switch? We use PyL at my institution, the Pylarify. Should we switch or onboard gallium now to give them lutetium PSMA? I thought that that was a little bit off because if we remember the PROfound study and this is again, something totally different, but PROfound study was looking at olaparib in the mCRPC setting. That had a companion diagnostic of next-gen sequencing specifically with foundation medicine to find a mutation that's actionable or pathogenic in BRCA2, 1, ATM, et cetera.
Does that mean that we all have to switch to using just foundation for our NGS? Or is there an NGS through Tempus or Caris functionally equivalent? Maybe it's a little bit of a stretch, but I was seeing it the same way. If it's apples to apples, I think that it qualifies the patient, and I was glad to see that the NCCN came out where it did. I think that the payers are going to see things functionally equivalent too.
There are already a lot of problems implementing some of these specialized technologies. In fact, a lot of patients, even in my practice, very excited about lutetium PSMA. I'm a urologist so I don't even see many of these patients, but they can't get it. They don't know where to get it because of supply chain issues, so why make an additional barrier to everyone for a functionally equivalent thing? Now, a lot of that is me sort of soapboxing, but the reality is the NCCN, I think, in concept agreed with that idea that these are similar tracers looking at similar molecules.
Alicia Morgans: Well, thank you so much for talking that through because at the end of the day, what I want most for patients is access to therapies that can improve their quality of life and lengthen their lives, and not having barriers is so important to that. This is something that I think will reduce barriers for our patients. So thank you for your time and for your expertise.
Ashley Ross: Thank you.