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

Alicia Morgans: Wonderful. Our next patient is JR. He is a 68-year-old man with a history of coronary artery disease and hyperlipidemia. He works as a computer scientist. In November 2021, his PSA was 6.4. In December, he underwent a prostate biopsy that showed Gleason 4+4=8 grade group 4 disease in six cores on the left, and he had Gleason 4+3=7 grade group 3 disease in six cores on the right. In January, he underwent a CT abdomen/pelvis that was negative for metastatic disease, but did show an enlarged prostate, and he also underwent a bone scan that was negative for evidence of bone metastases. He saw medical oncology, he also saw urology. His imaging was reviewed and the team decided to send him for a PSMA PET scan, so let's take a look at that.

Heather Jacene: For this patient, we didn't have the images, they were done outside on his bone scan and his CT scan, so we just have the PSMA PET scan to show. And so if we start again with the prostate gland, you have bladder, but then there were multifocal areas of PSMA uptake from the base to the apex, anterior and posteriorly, they extended to the midline here. But then he had several findings outside of the prostate gland, which included a left perirectal node. The images are a little bit misregistered, but you can see the focal uptake with this blue arrow. And then there was about a 3 millimeter lymph node in the left per rectal area, and then as we go superiorly, there was a second, about 5 millimeter, node in the presacral area. Again, a little bit misregistered, but we can see that there's PSMA uptake that's associated with that small lymph node.

The other finding on the scan, which was interpreted and thought to be benign, was he has a little bit of focal uptake at the costochondral junctions, which is low-level and a very good place for trauma. So this was right as disease within the prostate, and then those two small lymph nodes as positive for prostate cancer.

Alicia Morgans: Thank you, Heather. Adam, what do you think about those nodes? I guess two questions. Is this a patient you would've taken to surgery without question, given his negative conventional imaging before? And then, does this imaging change your plan?

Adam Kibel: Right. Prior to ha having PSMA PET, there's absolutely no question I would've operated on this patient. He has high risk disease. I took with the decision to operate a certain amount of risk that the surgery itself would not be effective and that he might require additional therapy afterwards, but I would feel this would be his best opportunity for cure in this relatively young, healthy individual.

PSMA PET has sort of changed our algorithm around this. This is not forwardly positive disease, but in the setting of somebody who has Gleason 9 prostate cancer in multiple cores, we're not talking about one core with like 10%, 20% of a core, we're talking multiple course, this gentleman clearly has bad prostate cancer. I think you have to take these findings very seriously. I might have viewed it a little differently if he had, let's say, Gleason 3+4 or low-volume disease, but in this setting, I think we have to treat it seriously.

And then I look at the PSMA PET and say, "Can I remove all the disease? Is it possible I could remove all the disease?" And yes, if something's in the primary landing zone, in the obturator and other pelvic lymph nodes are very close to the prostate, yes. Maybe the perirectal lymph nodes I could remove those, it could be very difficult to remove, but it's plausible. But the presacral one is totally outside of the field of dissection and the patient would almost certainly fail. In contrast, it's going to be within potentially the field of radiation therapy, and potentially the patient will achieve a better curative result if they get radiation than surgery. Again, we're still learning about these scans, we're still learning about how to integrate this in this algorithm, so my views on this may change, but right now, that's sort of how I'm thinking about

Paul Nguyen: Just to stay on that topic for a moment, Adam, how hard is it, or how easy is it, to localize one of these nodes and find it and pluck it out, let's say, if it is in your field of dissection?

Adam Kibel: I would say you're essentially taking out all the lymph nodes in an area, and the days when you used to operate on somebody and they'd have bulky lymph nodes that sometimes were very dark in color, I saw metastatic cancer where there were black lymph nodes, you don't see that anymore. And these are quite small lesions. So I think they're going to look like normal tissue.

My hope is that PET imaging is just one piece of how we're going to use these kinds of tools in order to better treat our patients. And I could imagine in the next 2, 3, 5, 10 years we'll have wands which will take to the operating room for somebody like this and find that metastatic deposit and remove it. At the current time, that's not routinely available, and so I think we can't depend on it. And even when it is routinely available, that still doesn't mean that we get all the metastatic cancer, we remove what's visible, because clearly patients that have visible metastatic disease, even in the PSMA PET era, can have occult metastatic disease that exists, but even PSMA can't can't identify.

Alicia Morgans: Yeah. I think from a radiation perspective, Paul, is this an area that you would expect, that presacral area, are these areas that you can address with radiation?

Paul Nguyen: Yes. For a typical patient with high-risk disease, now we are including the pelvic lymph nodes. There was some data that came out this year suggesting that pelvic lymph node radiation can improve metastasis-free survival, although most of those events were based on PSMA PET, so it's not the standard conventional imaging metastasis-free survival. But yes, this presacral node I would definitely include in my field. We include most of, what we'd call, the pelvic nodes and some of the low retroperitoneal nodes.

We go all the way up to L4-L5 now, so we've been actually expanding our standard radiation treatment field. I was on one of the panels that tried to help remake this, Bill Hall was the first author, but it was based on, largely, the PSMA findings that we would see this disease up in the presacral space, up in front of L4-L5, and so now we've moved our border up to the interface typically of L4-L5.

That perirectal node would not be in the typical field, and so this is where the imaging would be very helpful, because otherwise I wouldn't have treated that. And now seeing this, we would have to wrap the field around and add rectal toxicity. It's still doable, I just wouldn't want to do it for every patient. And that's why it's not going to be in our standard field. But for a patient where you have PSMA evidence of a positive node, I think it's worth it.

Adam Kibel: Alicia, can I ask you a question?

Alicia Morgans: Sure.

Adam Kibel: You talked about the change from surgery to radiation, but there's also the additional systemic agents frequently in this patient population. So the STAMPEDE data would indicate that high-risk radiation patients deserve some additional systemic therapy. Do you want to comment on that or am I incorrect?

Alicia Morgans: No, no, of course you're correct. Absolutely. [inaudible 00:08:21] and the STAMPEDE team presented and then published some data from STAMPEDE looking at the non-metastatic, but high-risk and very high-risk patient population, really demonstrating that these patients with locally advanced clinically node-positive disease who were included in that cohort do seem to benefit with the intensification of ADT plus abiraterone for a 2-year treatment duration. And so, usually patients like this who, they're clinically positive on PSMA PET only, so it's extrapolating that data a little bit, but we are intensifying in practice to give them the benefit of that survival advantage that we saw. Whether they really reap that reward I think remains to be seen, because, of course, it wasn't a PSMA PET-positive group that was included in that lymph node-positive group. But I think that we think that the odds are that they will benefit, and the toxicity is low enough that we're offering, and we're getting approved, abiraterone for intensification of this patient population.

So, let's see what this patient did. This patient decided to move forward with radiation and ADT plus abiraterone for a 2-year duration. So really taking advantage of this PSMA PET to not only change from a surgical approach to definitively going towards radiation, but also, I think, changing the radiation plan based on that perirectal node and getting the benefit of abiraterone intensification based on the STAMPEDE data for that 2-year duration. So multiple changes because of this PSMA PET. Thank you guys for talking this through.