Alicia Morgans: Hi, I'm so excited to be here from the Dana-Farber Brigham Cancer Center, where we have colleagues across a multidisciplinary specialty team to really talk about patients and think about how we can integrate PSMA PET scans into their care. Let's start with Dr. Kibel. Can you introduce yourself, please?

Adam Kibel: Sure. Hi, I'm Adam Stewart Kibel. I'm the chief of urology at the Brigham and the Dana-Farber. It's a pleasure to be here today.

Alicia Morgans: Wonderful. Thank you. And Dr. Nguyen?

Paul Nguyen: Hi, I'm Paul Nguyen, head of genitourinary radiation oncology at the Dana-Farber Brigham and professor of radiation oncology at Harvard Medical School.

Alicia Morgans: Thank you. And Dr. Jacene.

Heather Jacene: Hi, I'm Heather Jacene. I'm the clinical director of nuclear medicine at Dana-Farber and the assistant chief of nuclear medicine at Brigham and Women's Hospital.

Alicia Morgans: Great. Thank you all. Let's get started. This is patient DB. He's a 64-year-old man with a history of diabetes who came into his local urologist with concerns of irritation on voiding for nine months despite treatment with tamsulosin from his PCP. In March of 2022, he had a PSA of 67.8 and in April he still had an elevated PSA at 56.4. In April, he also had an MRI that showed possible capsular extension on the left with a 4.4 centimeter PI-RADS 5 lesion and possible seminal vesicle involvement. In May of 2022, he had a prostate biopsy. This showed Gleason 4+4=8, grade group 4, prostate adenocarcinoma in three cores on the left, and Gleason 4+3=7, grade group 3 in nine cores bilaterally with some potential perineural invasion. In June of this year, he had a bone scan in a CT of the abdomen and pelvis that was negative for radiographic evidence of metastatic disease. Of course, he was seen by our multi-d team and we reviewed all of the imaging at that time. In July, we requested a PSMA PET scan, and now we're back to review the imaging. Let's see what that all shows.

Heather Jacene: Okay, so this patient came for his PSMA PET/CT scan. If I start down in the pelvis with the prostate gland, we can see that there's very diffused heterogeneous uptake really throughout the gland and the posterior left side of the gland, there was an area of more intense PSMA uptake. There was also a suggestion here for some extra prostetic extension. But it's true as you scroll up towards the top, we have the bladder anterior, but there's also PSMA uptake that looks like it's extending into the left seminal vesicle. In addition to the disease in the prostate gland that we found identified several lymph nodes, which were actually scattered. There was a right sided, internal iliac lymph node right here, which was actually very small on the CT scan, probably about four to five millimeters. And then as you keep scrolling up, in addition, there was a very intensely PSMA-avid left common iliac lymph node, which was measuring about seven or eight millimeters. And so those were the two additional lymph nodes that were not detected on the diagnostic CT scan that PSMA added to his disease burden.

Alicia Morgans: Great. Thank you, Heather. So guys, let's talk this through. There are definitely some findings outside of the prostate. The prostate itself is not looking good. Paul, what do you think?

Paul Nguyen: Yeah, I would say this is a patient who... Before the PSMA PET given his very high PSA, I would've been concerned that there is some disease outside the prostate. I would've been concerned that a PSMA might find something like this. And so if we didn't have the imaging, I would probably recommend for him radiation and hormone therapy. I'd treat the pelvis and do the prostate boost. I think, but still at the time I think surgery would've been reasonable and happy to hear it from Adam about that. But I think now with the PSMA PET showing a very avid node where we would expect it and kind of lining up with the PSA of 60, I would strongly favor radiation and hormones for this patient.

Alicia Morgans: Yeah. I think, from my perspective, these are the cases where you think, "Gosh, I would have thought that that conventional imaging with technetium bone scan and CT would be positive." And so it's very reassuring to have the PSMA PET imaging to help us see what we couldn't see before. So Heather, just to clarify, you pointed out a lymph node that was quite avid and that lymph node is only four millimeters. So that's not something that anyone's going to call on a CT scan as being a positive or even concerning lymph node, is it?

Heather Jacene: No, it's does not meet size criteria and you see normal size lymph nodes like that all of the time. If we called all of those positive on CT, we'd have a lot of false positive CT scans. But here the PSMA PET is just adding the specificity really to the test. And that's really why we do functional imaging because you can see things earlier than you can see the size change on a CT scan alone.

Alicia Morgans: Really, really helpful. So, Dr. Kibel, what do you think about surgery in this patient?

Adam Kibel: I would be very concerned that he's just going to have a recurrence. I think the key thing is he needs some form of systemic therapy and I think surgery will delay that. I can't prove that a delay of a month or two is going to make a huge difference, but I always get concerned about it. I think that many people extrapolate the data from HORRAD that patients are going to benefit, they're going to benefit from radiation with micrometastatic disease that's visible on say PSMA, it would be true for surgery as well. I think that remains to be proven. And so therefore I think both from a radiation and from a systemic therapy perspective, this is somebody who probably should progress immediately to radiation and systemic therapy.

Alicia Morgans: You make a such a good point there. When I imagine... Of course, this is all imaginary. We don't have actually live biologic data showing metastatic disease. But when I imagine the spread to these small lymph nodes, I also imagine that there could be micrometastatic disease that's not picked up even by the PSMA PET. And radiation gives us the opportunity to bathe that pelvic area in some radiation plus the systemic therapy as you mentioned. And so that combination to me gives us a little bit more of a safety net. What are your thoughts?

Adam Kibel: Well, I agree with you 100% and I think that you treat the local disease with the radiation. You treat some of the regional disease with radiation, and Paul can comment on that more than I can, but pelvic radiation appears to be the standard of care for a patient like this. I'd rather Paul said that than I did, but. And then lastly, you treat the systemic therapy, I think not only is going to treat those lymph nodes, but as you nicely outlined, if the patient has micrometastatic disease elsewhere in their body, which I think is highly likely on the base of that imaging sub four millimeter. We're talking about a few cancer cells. The systemic therapy will hopefully eradicate those. Paul, do you want to comment?

Paul Nguyen: Yeah. So just about two years ago, there was this kind of consensus analysis of PSMA PETs to try to figure out what the best areas are to radiate in the pelvis. And we're talking about areas that aren't definitively positive. And this was an effort led by Bill Hall and several NRG members was a part of this and I got to be a part of it as well. But what we found was that thanks to the PSMA PET imaging, there were new areas that we were finding that we weren't necessarily covering before in our pelvic lymph node field. So for example, covering kind of a little bit up higher in the periaortic above L5, so we used to have our top board at L5. Now it's closer to L4, L5, and then we'd pull a little bit lower on the presacral. Some PSMA were showing some disease there. And so I feel like thanks to PSMA, we've been able to refine what we prophylactically treat in the pelvis with radiation. And so for this patient, I would apply that larger prophylactic field. And then we'd give very specific boost doses to those two lymph nodes that were identified.

Adam Kibel: I think one of the things that's really incredible about PSMA PET is it's actually changing our therapeutic paradigm. And so in the past, I mean Heather can comment on this more than me, but really radiology is around identifying disease and then the job is done. But I think with PSMA PET, we're going to start seeing patients that get PSMA PETs actually having better outcomes, simply because we can tailor their therapy better. And this is a good example of radiation of the pelvic area is a perfect example of our practices being changed on the therapeutic side, as well as the diagnostic side.

Paul Nguyen: Yeah, I mean, to that point, there was a beautiful study by Ashesh Jani out of Emory published last year, the Empire-1 trial that looked at fluciclovine PETs and was the first study that I've seen that randomized patients to PET versus no PET and found that just randomization to PET improved progression-free survival, quite significantly, very significant hazard ratio of like 0.5. So exactly to your point, Adam, that an imaging studies actually improving outcome significantly now.

Alicia Morgans: Great. Well, I certainly agree. And this patient with these risk factors meets criteria, I think for intensification. So let's see what happened. So Mr. DB was started on ADT and abiraterone per the STAMPEDE criteria. He does have plans for systemic treatment for two years with external beam radiation to the prostate bed and pelvis. And I'm sure he'll get some boost as well. And that is going to start about two months after the initiation of his systemic therapy. So sounds like he is taking your advice. Thanks, guys.

Paul Nguyen: Thank you.

Adam Kibel: Thank you.