Phillip Koo: Hello. It brings me great honor and joy to welcome Jeremie Calais to UroToday. Jeremie is an Assistant Professor of Radiology and Nuclear Medicine at UCLA and also the Clinical Director of the research program in the Department of Nuclear Medicine and Pharmacology at the University of California Los Angeles. Jeremie today provided a wonderful plenary lecture on the importance of PSMA imaging in patients with localized cancer here at GU ASCO 2020 in San Francisco. So, welcome Jeremy, to UroToday.

Jeremie Calais: Hi Phillip, thanks for the introduction.

Phillip Koo: So first of all, you know you've had an amazing couple of years with regards to all the research work that you've published in prostate imaging and therapies. So thank you for all that work. Today you focused on the utility of PSMA imaging in patients with presumed localized cancer or patients who present with initial diagnosis of prostate cancer. For those who weren't able to attend, can you give us a brief synopsis of that and what recommendations you would have for patients in that setting?

Jeremie Calais: So we talk again about PSMA PET imaging. So this targeted agent for localizing prostate cancer cell that do express this PSMA at the surface of the cells. With that you can stage the prostate cancer, many different indications for that. Basically you localize where the prostate cancer cells are. Most of the studies are done in the recurrent setting, meaning after the disease comes back after primary therapy. But like I said, you can localize where the prostate cancer cells are, so why not doing it earlier, before any initiation of any primary therapy. So today we focus mostly on the primary staging of patients. The main interest of a whole-body imaging scan like that is to detect if the disease has spread out outside of the prostate or not, which completely changes the treatment indication of course.

So it's a whole-body imaging modality. It can show where the prostate cancer lesions with high sensitivity is, and the more a patient is likely to have an extraprostatic disease, the more likely he needs to get a PSMA scan to be stage. So for a low-risk patient with a disease that is not very aggressive, that is not very likely to be going out outside of the prostate. Maybe the scan is less relevant, although we can also discuss that and find many indications there. But for high-risk disease, risk for being outside of the prostate and being aggressive... Here, clearly PSMA PET has a huge impact because it can show lesions that were not seen before in any conventional imaging.

Phillip Koo: Great. So I guess the question becomes what do urologists do with that information or radiation oncologists? And I think when you had that high-risk patient who might have negative conventional imaging and then you have a widespread disease on the PSMA PET, which someone showed an example of that. I think it's pretty obvious that maybe that patient would benefit more from systemic therapies and not have any definitive therapies. But patients who might have one or two mets... I don't know if we had the data to say that this patient should not get definitive therapy. Your thoughts on sort of that whole treatment question?

Jeremie Calais: So this is clearly the topic of the moment and I think in the next decade we may have new diagnostic tools that also show more disease at earlier stage and we need to redefine again and again how we treat the patient based on the staging we have in hands. As of now, PSMA is new, but it gives new information that you cannot close the eyes on. You just see more than this than before. You don't see all, the sensitivity is not perfect, you just still see only the visible imaging part of the iceberg.

But before we kind of have all the data on conventional imaging and the treatment, how they were performing based on their staging. So an M0 patient, we have data on that, but now a conventional M0 patient can be M1 with PSMA, so what do we do with that? From my experience at UCLA for radiation oncologists, when you have maybe oligometastatic setting less than five or three lesions, they tend to treat them, they just add a new target.

If you have lesions that were not seen on conventional imaging that show up on PSMA that is close to the radiation field, they just extend the radiation field to include it. Sometimes they do some booster needs. So for radiation oncologists that already are using usually concomitant ADT with radiation therapy, they just have to adapt a little bit their field, maybe add other lesions and I think they will still continue to treat the primary, the lesions that are seen, and add ADT on that.

Phillip Koo: Correct.

Jeremie Calais: For surgeons, maybe different questions because usually, it goes towards upstaging patients. Sometimes we have some cases where we downstage you have like weird findings on the bone scan and you downstage the patient, but usually, you see more disease than on conventional imaging. But so for a surgeon that wanted to do, for example, nerve-sparing, you see T3b disease, prostate cancer is outside of the prostate, you cannot do this nerve-sparing anymore so it will go to radical prostatectomy.

And if you see disease outside in the pelvic nodes, it means probably the disease is already spread out also somewhere else, you just see it more. And so these patients that were prior, they were getting surgery... Now, for example at UCLA, the surgeon tends to not do surgery on these patient anymore. The true outcome of that, we don't have follow-up yet, so it's hard to say this is better or not. It's just that when you see disease outside, it's difficult for a surgeon to say, "Okay, I'll still remove your prostate cancer even if I know that there is disease outside". It's difficult from that point of view.

Phillip Koo: So you mention sort of the limitations of PSMA PET/CT. In today's lecture, you talked about N1 disease in roughly two-thirds of cases being missed with PSMA PET/CT. Can you talk a little bit about the inability to detect some of the micromets presumably in these nodes?

Jeremie Calais: I have to mention first before I talk about that, that all these patients were negative per conventional imaging. So conventional imaging was 0%. And in that, you take maybe 30, 40% that become N1. And you still have the one that no imaging is able as of now to detect this metastasis. The main limitation and the main reason is the size of the micrometastasis. Too small to be detected. You just see the imaging part of the iceberg.

Phillip Koo: So the last question I have is you talked a little bit about the use of PSMA to evaluate the primary tumor in the prostate gland and there's been data that talks about the complementary aspects of PSMA PET/CT with MRI. Can you sort of expound upon that for us?

Jeremie Calais: Yes. When you look at either PSMA MRI studies or head-to-head direct comparisons with the pathology as a gold standard, usually you see some overlap. Clearly you have the main cancer that is pretty well curated. Then you always have a portion of the MRI that is not seen on PSMA and usually, you have more disease on PSMA PET as well that is missed by MRI. So for bilateral disease, additional cancer types, we don't know the clinical significance of this, but usually, PSMA shows more. So again, it would go towards upstaging the local staging. This can have an interest because now the standard of care is to do a biopsy either on a template basis or guided with MRI, but many times it comes back negative and you don't know, you still have a high suspicion of prostate cancer in the patient, your biopsy comes back negative, the MRI is equivocal. PSMA can play a role to better locate the disease to target the biopsy.

Also, you have this huge debate of what is a clinically significant cancer that you have to treat one that you can just watch and wait and it's okay to not do anything, Gleason 6 low-grade disease or the more aggressive one. And it seems that in the primary cancer, the intensity of uptake is correlated with the Gleason grade. Like the Gleason 3, 4, 5 would have a higher uptake than the grade 1 and 2. And with that, you can imagine that if you do a PSMA PET in a patient and that you see nothing in the prostate, it's okay to not have a diagnosis, this patient has a good prognosis and you should see a focus. It's more likely that it's a grade three, four, five and you need to act on it.

Phillip Koo: Great. I love that idea. It's sort of smarter imaging being able to us to give us reasons not to intervene or maybe give us reasons to intervene in these patients. Thank you so much, Dr. Calais, for joining us and for all the work you've done for the urologic oncology community, so thank you.

Jeremie Calais: Pleasure.