Alicia Morgans: Hi, my name is Alicia Morgans and I'm a GU Medical Oncologist at Dana-Farber Cancer Institute. I'm so excited to share with everyone a Dana-Farber Cancer Institute Prostate Cancer Tumor Board, where we're really evaluating and investigating the use of PSMA PET in the care of patients with prostate cancer. Let me introduce my colleagues. First, Heather Jacene.

Heather Jacene: Evening, everybody. I'm Heather Jacene the Clinical Director of Nuclear Medicine and PET CT at Dana-Farber.

Alicia Morgans: Thank you. Next, Dr. Paul Nguyen.

Paul Nguyen: Hi, everyone. I'm Paul Nguyen. I'm the Head of the Genitourinary Radiation Oncology group at Dana-Farber and Professor of Radiation Oncology at Harvard Medical School.

Alicia Morgans: And last but not least Adam Kibel.

Adam Kibel: I'm Adam Kibel. I'm the Chief of Urology, both at the Dana-Farber Cancer Institute and at the Brigham Women's Hospital. Excited to be here today.

Alicia Morgans: Wonderful. So our next patient is Mr. KM. He's a 64 year old man with a history of kidney stones. He works in real estate development. In August 2021, he had a PSA of 5.7. In November, it had increased to 5.95, and in December it was 10.48. That's when he underwent a prostate MRI that showed a PI-RADS 3 lesion on the right. In January, he underwent a prostate biopsy that showed Gleason 4+4=8, grade group four, in four cores on the right. And Gleason 4+5=9, grade group five, in one core on the left. As well as some Gleason 4+3 in three cores on the left. In January, he underwent a CT abdomen and pelvis that was negative for definitive metastatic disease, but he did have some bone islands in iliac bones and the left femoral head. And in January he had a bone scan as well that was negative for evidence of bone metastases.

So he saw medical oncology and urology. The imaging was reviewed. And then in March, the team tried to order a PSMA PET. But due to insurance restrictions, he ended up undergoing a fluciclovine PET. And then the case was reviewed.

Dr. Jacene, can you talk us through the images please?

Heather Jacene: Sure. So you... This is a fluciclovine PET CT scan, which has a very different biodistribution compared to a PSMA PET. So right away you'll... You can see that there's no lacrimal or salivary gland uptake. You also don't have as much activity in the kidneys and the bladder. You do... And then on this fluciclovine you do see the structure in the upper abdomen, which is the pancreas.

When you go to the prostate gland in this patient, you can see that there's some low level fluciclovine uptake on the right side of the prostate gland, which... Where the PI-RADS 3 lesion was. But there was more impressive fluciclovine uptake that was actually on the left hand side of the gland.

And then in addition to that, the disease within the prostate gland, there was a small lymph node that was just in the fat, just anterior to the prostate gland on the right that also had fluciclovine uptake.

We didn't see any disease that was outside of the prostate and that single lesion just in front of the prostate gland.

Adam Kibel: Heather, I know we got this for insurance reasons as opposed to getting a PSMA PET, but is there any data in any disease state that shows us that one is better than the other?

Heather Jacene: Sure. So there's one study by [inaudible 00:03:22] in the setting of early biochemical recurrence, where they directly compared fluciclovine PET CT to PSMA PET in the same patient population. So it wasn't randomized. But both... But patients got both scans. And what they ultimately showed was that if you look within the prostate gland itself, the fluciclovine and the PET, the PSMA PET performed similarly in early biochemical recurrence. But when you look at both nodes, lymph nodes in the pelvis and then distant metastatic disease, PSMA PET is more sensitive in all of those areas for the detection of the disease. Of the disease itself.

Alicia Morgans: Well, thank you for talking that through. Adam. What... What are your thoughts in terms of surgery as an option for this patient based on the imaging and the discussion you've had with your team?

Adam Kibel: So, clearly that this lymph node is in the... Is in the periprostatic fat, which... I think often we don't think of as a place where metastatic disease can occur. But I will tell you, this is not the first patient that I've seen that has metastatic disease in this location.

I think it's very curable disease because you can actually remove this metastatic deposit. I think in some sense the imaging, in this case fluciclovine but also PSMA, is reassuring that there's not metastatic disease elsewhere.

So if you feel confident you're going to be able to remove all the disease, I think it's definitely worth doing. And that's how I'd proceeded with this particular case.

Alicia Morgans: Thank you for that. And Paul, I imagine this is something that if the patient wanted radiation, you could radiate that area.

Paul Nguyen: Yes. So our normal field probably would capture that periprostatic node there. But seeing this on the scan, I would be sure to extend the field a little bit, just to make sure we had a wide safety margin around that. And then I would also treat the pelvic nodes as well. Once it's there, I would imagine that it... That there's certainly a risk that it could be elsewhere. So I'd include the standard pelvic nodal field.

Alicia Morgans: Great. So let's look at what happened to this patient, and then we'll talk... We'll talk that through. So this patient moved forward with... Forward with surgery with Dr. Kibel. He had pT3bN1 disease, Gleason 4+3 with the presence of pattern 5 at surgery. His post-op PSA is still pending.

Dr. Kibel, what are your thoughts on whether this patient is finished or is this a patient with high risk disease who might need something more?

Adam Kibel: I'm actually a little more concerned by the p3b disease than the N1 disease. That's a sign that it's fairly aggressive. The lymph nodes was just in that one location. The... Actually, the fluciclovine scan was completely accurate. The pelvic lymph nodes were completely negative. But some [inaudible 00:06:18] invasion I think means it's highly likely to be recurrent in the pelvis and also much more likely to have metastatic disease.

I still believe the data that salvage radiation is as effective as adjuvant radiation. And so I in general follow these patients. And if their PSA starts to increase, at that point they would get... They would get additional radiation and probably some systemic therapy as well given the fact that he had N1 disease.

If the patient wants to talk to our radiation oncology colleagues, I freely refer them to them. And Paul Nguyen sees an awful lot of my patients that are in this exact situation and discusses that with them as well.

Alicia Morgans: Well, that's great to hear. I think the PSA post-op will be probably one of the pieces of the puzzle that will help make that decision. And... And Paul, I have a feeling that you're... You're a proponent of early salvage when appropriate, too?

Paul Nguyen: Yes. I think certainly in the node positive setting there is some rationale to deliver the radiation and hormones adjuvantly, even with a zero PSA. But I think that it should be generally safe to wait until the PSA goes up a little bit before we jump in and do some early salvage. So I am generally fine with early salvage in this setting.

And we in fact have two randomized trials open that look at the question of early salvage radiation for these kinds of patients. One is the iNNOVATE trial, which is a... An RTAG trial for patients with a detectable PSA in this setting, where they get randomized to standard hormones or Apalutamide with standard hormones. And then the DASL-HiCaP trial where we look at adding Darolutamide to standard hormones.

Adam Kibel: Paul, are there any settings in which genomic testing will help you decide whether you should proceed with immediate adjuvant radiation or whether you should wait for salvage?

Paul Nguyen: I think that's a great question, Adam. I think there's been so much more data that's come out of... About the value of genomic testing. Particularly the Decipher score in the post-op setting. I think perhaps at the pT3bN1 this is already aggressive enough that we know what we... We've already made up our mind either way. But I think for a lot of the borderline cases that are a little bit less aggressive than this, I think genomic testing can be quite useful in that high genomic scores may argue for adjuvant therapy whereas perhaps with lower scores you can watch and do early salvage. Although that's still kind of extrapolating a lot from retrospective data at this point.

Alicia Morgans: Well... And a quick question for Dr. Jacene. If this patient ends up having adjuvant. For example, adjuvant radiation. And then we continue to follow and then the PSA starts to rise in a biochemical recurrent sort of a way. What's the PSA at which you would recommend consideration of PSMA PET? That's a... It's a question that is commonly asked of patients or patients are asking us all the time. And I know what I say, but I'd love to hear what you say.

Heather Jacene: So I think that we know from the data that the higher the PSA level is the more likely that your PSMA scan is going to be positive. I think 0.5 is probably a good base number to kind of start with, but also at lower PSA levels. Also in considering the doubling time, the faster doubling time. Also, it's more likely to have a positive... A positive scan.

I think we're seeing PSMA scans being done at lower PSA levels. And we'll probably... There's very little data less than 0.2. And so I think as we do more scans potentially at lower levels, we'll... We'll even learn kind of that space between 0.2 and 0.5, where a good spot might be.

Alicia Morgans: Well, thank you for that. Now there's... That was a... Maybe the easy version of the question. The harder version of the question is the question that I know Paul gets and Adam gets. Which is a patient who has not had radiation after the prostatectomy and their PSA is rising. So we're trying to decide now between early salvage and when do we get the PSMA PET? And how does that all work together so that we can do the salvage as appropriate, but also identify if we should be doing SBRT to something in addition to radiating the pelvis in that setting?

All right, Adam and Paul. What do you think in that setting?

Paul Nguyen: So we're talking about they've had surgery, they haven't had radiation and we want to kind of figure out when to scan them. Well, I think...

One thing I want to talk about is sometimes in this setting you'll hear people say, "Well, maybe we should keep following them with serial PSMAs until we find something positive to radiate." And I think that's a mistake. I think that's an outright mistake. I think we know very clearly that radiating when the PSA is lower, gives you a better chance of cure. And I think the whole concept of waiting until you find a single target to identify is just a mistake. And I hope that people are not doing that in general.

I tend to get the PSMA, personally, when the PSA hits about... Around 0.25. That feels like a time where we might see something. And below that usually I don't get the PSMA. And if we see something at that point, fine. We'll... We'll radiate, but if we don't see something we'll still radiate.

So that's kind of my view on that. And in fact, I use a 0.1 cutoff, generally, to start radiation. And I wouldn't wait until 0.25 just for the PSMA. I would just go ahead and treat them at 0.1.

Adam Kibel: I don't think it's surprising that Paul and I view this very similarly. If I see a patient that decides to be observed and only get radiation, if their PSM... PSA increases. By the time it gets to 0.1, they're seeing... They're seeing one of my radiation oncology colleagues. And at that point, I don't think a PSMA PET is very useful.

I'm trying to think of a clinical scenario where it would be. I think it... That would be patients that have incredibly high risk disease where their PSA doesn't nadir after surgery. Or somebody who has a very early recurrence, like within the first three to six months. I'm thankful that those patients are fairly rare, even in my practice. And I mostly operate on patients with very high risk disease. And even in that, in my practice, that's relatively rare phenomena.

Alicia Morgans: Well, I'm glad to hear that. And I expected those answers because I practice with the two of you, too. But thank you both for really emphasizing that salvage radiation to the pelvis is still standard of care. We should not just be waiting and repeating serial PSMA PETs and then only radiating if we see something. Because we have the opportunity to cure some patients with salvage radiation. And if we can add on some SBRT to some other lesion or maybe change the field of salvage radiation because we find something, that's great. But we should not be delaying or not even using salvage radiation just because we're waiting for a PSMA PET to be positive.

So thank you guys for talking that through. And thank you, Heather, for talking us through when we should think about it in the post... Maximal local therapy setting. Which is also a setting where we're trying to think about how do we best time this and find that remaining disease.

So thank you guys. And I wish luck to this patient. I'm hoping that his PSA is undetectable. I know he had a great surgeon. He still has a great team. So hopefully all will go well. Thank you guys for talking this through.