Alicia Morgans: Hello, my name is Alicia Morgans and I am a GU medical oncologist at Dana-Farber Cancer Institute. I’m very excited to share with everyone, a Dana-Farber Cancer Institute prostate cancer panel, where we’re really evaluating and exploring the use of PSMA PET in the care of prostate cancer patients. Allow me to introduce my colleagues. First up, Heather Jacene. Heather Jacene: Evening, everyone. I’m Heather Jacene, the Clinical Director of Nuclear Medicine and PET/CT at Dana-Farber. Alicia Morgans: Thank you. Afterwards, Dr. Paul Nguyen. Paul Nguyen: Hi everyone. I’m Paul Nguyen. I am Chief of the 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 am Chief of Urology at both Dana-Farber Cancer Institute and Brigham and Women’s Hospital. I am thrilled to be here today. Alicia Morgans: Great. Our next patient is JR. This 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 group 4 disease in six cores on the left and had Gleason 4+3=7 group 3 disease in six cores on the right. In January, he had an abdominal/pelvic CT scan that was negative for metastatic disease but showed an enlarged prostate and also had 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 out with his bone scan and his CT scan, so we only have the PSMA PET scan to show. And so if we start again with the prostate gland, you have a bladder, but then there were multifocal areas of PSMA uptake from the base to the apex, anterior and posterior, extended to the midline here. But then he had several findings outside the prostate gland, which included a left perirectal nodule. The images are a little off, but you can see the focal uptake with that blue arrow. And then there was a lymph node about 3 millimeters to the left per rectal area, and then as we move up, there was a second, about 5 millimeter, node in the presacral area. Again, a bit of a mislabel, but we can see that there is PSMA uptake associated with this small lymph node. The other finding on the scan, which was interpreted and considered benign, was that he has some focal uptake at the costochondral junctions, which is low-grade and a very good place for trauma. So that was right as disease within the prostate, and then these two small lymph nodes as positive for prostate cancer. Alicia Morgans: Thanks, Heather. Adam, what do you think of these hubs? I guess two questions. Is this a patient you would take to the operating room without question, given his negative conventional imaging in the past? And then, does this visualization change your plan? Adam Kibel: Right. Before doing PSMA PET, there is no doubt that I would have operated on this patient. He has a high-risk disease. I took with the decision to operate a certain risk that the operation itself would not be effective and that additional treatment might be needed afterwards, but I would feel that this would be the best opportunity for treatment in this relatively young, healthy individual. PSMA PET has somewhat changed our algorithm around this. This is not forward-positive disease, but in the context of someone who has Gleason 9 prostate cancer in multiple cores, we’re not talking about a core with about 10%, 20% of a core, we’re talking about multiple course, this gentleman clearly has a bad cancer of patron. I think you should take these findings very seriously. I might look at it a little differently if he had, say, Gleason 3+4 or low-volume disease, but in that setting, I think we have to take it seriously. And then I look at the PSMA PET and say, “Can I remove all the disease? Is it possible to remove all the disease?” And yes, if something is in the main 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, they could be very difficult to remove, but it is possible. But the sacrum is completely out of the scope of dissection, and the patient would almost certainly fail. Instead, it will potentially be within the scope of radiation therapy, and potentially the patient will achieve a better therapeutic outcome if they receive radiation from surgery. Again, we’re still learning about these scans, we’re still learning how to integrate it into this algorithm, so my views on this may change, but right now, that’s how I think Paul Nguyen: Just to stay on that for a moment, Adam, how hard is it, or how easy is it, to locate one of these nodes and find it and remove it, say, if it’s in your dissection domain ? Adam Kibel: I would say you basically take out all the lymph nodes in an area and back in the day when you were operating on someone and they had massive lymph nodes that were sometimes very dark in color, I saw metastatic cancer where there were black lymph nodes, you don’t see that anymore. And these are very minor damages. So I think they will look like normal tissue. I hope that PET imaging is just one part of how we will 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’re going to have rods going into the operating room for someone like him and finding that metastatic deposit and removing it. At present, this is not usually available and so I think we cannot depend on it. And even when it’s routinely available, that doesn’t mean we’re getting all the metastatic cancer, we’re removing what’s visible, because clearly patients who have visible metastatic disease, even in the PSMA PET era, may have occult metastatic disease that’s there , but even PSMA cannot recognize. Alicia Morgans: Yes. I think from a radiation standpoint, Paul, is that an area that you would expect, that presacral area, are those areas that you can address with radiation? Paul Nguyen: Yes. For a typical patient with high-risk disease, we now include the pelvic lymph nodes. There have been some data released this year suggesting that pelvic lymph node irradiation may improve metastasis-free survival, although most of these events were based on PSMA PET, so it is not standard imaging for metastasis-free survival. But yes, I would definitely include this pre-priestial node in my domain. We include most of the so-called pelvic nodes and some of the low retroperitoneal nodes. We’re going up to L4-L5 now, so we’re actually expanding our typical radiation field. I was on one of the panels that tried to help recreate this, Bill Hall was the first author, but it was based, in large part, on the PSMA findings that we would see this disease in the presacral space, in front of L4- L5, and so now we have moved our border to the interface usually of L4-L5. This perirectal node would not be in the standard field, and so imaging would be very helpful here, because otherwise I would not have encountered it. And now seeing this, we should wrap the field and add rectal toxicity. It’s still possible, I just wouldn’t want to do it for every patient. And that’s why it’s not going to be in our standard domain. But for a patient where you have node-positive PSMA evidence, I think it’s worth it. Adam Kibel: Alicia, can I ask you a question? Alicia Morgans: Definitely. Adam Kibel: You talked about the switch from surgery to radiation, but there are also the additional systemic factors often in this patient population. Thus, the STAMPEDE data would suggest that high-risk radiation patients deserve some additional systemic therapy. Do you want to comment on that or am I wrong? Alicia Morgans: No, no, of course you’re right. Absolutely. [inaudible 00:08:21] and the STAMPEDE group presented and subsequently published some data from STAMPEDE looking at the nonmetastatic but high-risk and very-high-risk patient population, really demonstrating that these patients with locally advanced, clinically node-positive disease that were included in this cohort seem benefit from intensification of ADT plus abiraterone for 2 years of treatment. And so, typically patients like him who, they’re clinically positive on PSMA PET alone, so we’re stretching that data a little bit, but we’re stepping up in practice to give them the benefit of that survival advantage that we saw. Whether they will actually reap that reward, I think, remains to be seen, because, of course, it was not a PET PSMA-positive group that was included in this group of positive lymph nodes. But I think we think the odds are that they will benefit, and the toxicity is low enough that we offer, and get approval for, abiraterone for intensification in this patient population. So, let’s see what this patient did. This patient decided to proceed with radiation and ADT plus abiraterone for 2 years. So, really taking advantage of this PSMA PET not only to change from a surgical approach to definitively going to radiation, but also, I think, to change the radiation plan based on that perirectal node and to benefit from the abiraterone boost based on STAMPEDE data for this 2-year duration. So many changes due to this PSMA PET. Thanks guys for discussing this.
