Dr. Moyad: So, you were here for ten years. What’s the greatest advancement that you saw in the ten years that you were here in Los Angeles beside the fact that probably pollution increased and traffic got worse?

Dr. Margolis: Well if we’re talking about prostate imaging, I think the thing that was most enlightening, and probably had the greatest impact was UCLA was one of the sites that helped develop PI-RADS which stands for Prostate Imaging, Reporting, and Data Systems. So PI-RADS is a uniform language for communication between physicians, not just radiologists, but oncologists, surgeons, radiation therapists, basically anybody in the health care community now has a simple and straightforward way to interpret MRI and understand the likelihood that a scan has a sight that suggests clinically significant disease.

Dr. Moyad: And PI-RADS is “P-I-R-A-D-S” correct?

Dr. Margolis: Correct

Dr. Moyad: And can you tell them essentially when they see it—when they see a note or they read about PI-RADS—what’s the numbers they might see and what do they mean to you? Just briefly, obviously we don’t want to keep you here for the next six hours.

Dr. Margolis: Fair enough. So it’s a 1-5 “score” or category system, and so category 1 is normal, meaning there’s no abnormality that we see. Category 2 is low-risk, so there are changes in the prostate, but they are most consistent with benign things like inflammation or prostatic hyperplasia (BPH). Category 3 is intermediate and so that’s where there’s something concerning but its not high likelihood; 4, high likelihood and 5 is very high. So what we know from surgery and from biopsy is a category 5 lesion or category 5 abnormality has at least 90% to 95% likelihood of having clinically significant cancer.

One of the things to keep in mind about PI-RADS is it's not just about communication. It’s about technical standards, about how we diagnose, and how we report, and how we communicate. And so looking for a imaging facility that uses PI-RADS should be reassuring to know that they are performing prostate imaging to the highest clinical standards. You still want to ask the question about how was your radiologist trained. What certification do they have? How do we know that this is a good radiologist? But you also want to know that they’re using PI-RADS unless you’re someplace like Sloan-Kettering or UCLA that has been doing this for so long and read so many cases that they have a system that is even better. So what we found is that PI-RADS is great for communicating across different institutions, and that’s why at UCLA we would report the UCLA score and PI-RADS because the assessment system we set up at UCLA used quantitative information and was very-slightly more accurate than PI-RADS, but we still need to communicate to other physicians so we also give the PI-RADS category.

Dr. Moyad: And all this was going on while you were in Los Angeles. The whole PI-RADS system developed. The one that you embraced is still the one that is used now, right?

Dr. Margolis: Yes

Dr. Moyad: And then you go to New York

Dr. Margolis: Yes

Dr. Moyad: What’s the most exciting thing you see happening in New York right now?

Dr. Margolis: The most exciting thing for me is PET/MRI. So we have a scanner that can an MRI and a PET scan simultaneously.

Dr. Moyad: WHY. Why would I want to do that? It sounds like you’re giving me a lot of excess radiation even though I know MRI doesn’t give radiation.

Dr. Margolis: Exactly, so one of the advantages of PET/MRI is that it’s less radiation than a PET/CT because you get the attenuation correction, the CT data, is provided by MRI [rather] than CT. In reality the relative amount of radiation between a PET/MRI and PET/CT is negligible, so I wouldn’t look for PET/MRI just because of the reduced radiation. The main advantage is that you get all of the tissue characterization and functional characterization from MRI along with the specificity of the PET agents that we now have for prostate cancer. So for prostate cancer, as you may know, FDG-PET is not useful.

Dr. Moyad: Aw! Terrible, right?

Dr. Margolis: Right, but good news. We have a number of different options. So choline and acetate have been used for some time and are very useful for men, especially with a PSA greater than 2. There is another agent which is commercially available fluciclovine (FACBC). The commercial name is

Chorus: Axumin

Dr. Margolis: Full disclosure, I do consult for that company because they want to know what is their performance compared with MRI, and they have shown excellent sensitivity with a PSA as low as 1 and even with .5. But the next agent which is still in experimental trials, but we hope to see come to the clinic within the next few years and is already clinically used in other countries like Germany and Australia is PSMA. The confusing thing about PSMA is that it’s not one agent. So my co-worker Neil Bander discovered this 20 years ago, it stands for Prostate Specific Membrane Antigen, and it is a component of the cell surface that is up-regulated in prostate cancer, and the PET tracers that detect it are very sensitive and specific for prostate cancer. The exciting thing is we now have different ways to target it. So the first way that we discovered was using antibodies. We can generate antibodies in an animal model and label them with a PET tracer, and so the antibodies thinking that the PSMA is a bacterium or a virus will glom onto it, and so that gives us excellent sensitivity. But we now have small molecules, so this protein, the PSMA, has a receptor for different kinds of small molecules, and we can make a small molecule that binds to it very tightly, and that way we can have something that has much faster kinetics so rather than waiting a few days for the PET scan, we can get the PET scan within an hour.

Dr. Moyad: So let me ask you this. Going back to this PET/MRI you’re doing, this PET/MRI. Do you think that’s where we’re going to be in the next 3-5 years? That these are gonna be done together to correct for each other, to make sure we’re getting the best possible scan? So if you had to put on your soothsayer hat will we be combining those five years from now at all these major medical centers?

Dr. Margolis: I think what we’ll see is we’ll have much better patient specific imaging choices. So for some patients, yes. You should get a PSMA PET/MRI because you need to characterize the prostate and the tissue around it to determine treatment, but you also want the sensitivity of PSMA for metastatic disease in lymph nodes and bones. For some patients, you would just need the PSMA data, that if you are mostly concerned with whether or not there’s metastatic disease, the PSMA will work just fine.

Dr. Moyad: Getting both of those together also is a time factor. It’s nice for the patient, right? If that was to work this way. It’s like going to see Scholz and then having Moyad right behind him to make sure, you know, I can provide some kind of alternative opinion.

Dr. Margolis: Right, both of you in the clinic at the same time talking over each other.

Dr. Moyad: Oh, that would be great. We’re really good at that.