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 Stuart 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. All right, everybody. Let's move on to our next patient. This is patient DM. He's a 72-year-old gentleman with no past medical history. He is a retired math teacher, and he is married. He's coming in with his wife. He has been followed for some time at this point. He had a PSA in December of 2021. That was 8.44.

In February of 2022, he had a repeat PSA that was 7.61, and his DRE was notable for having a left-sided firm nodule. In March of 2022, he underwent a prostate biopsy that was notable for Gleason 4+5=9 prostate adenocarcinoma. This was grade group five disease in six of 12 cores, and he did have some introductory features. In April of 2022, he had a bone scan that demonstrated mild uptake in the right ninth rib that was indeterminate and a CT of the abdomen and pelvis that demonstrated bone lesions in the left ilium and the right femur and a one-centimeter sclerotic lesion in the right ninth rib and mildly enlarged prostate with a mild protrusion into the bladder. No lymph adenopathy on that imaging.

He was referred to our center for a second opinion. Of course, we reviewed his imaging. It was notable for that indeterminate rib lesion. We discussed and ordered an MRI of the prostate and a PSMA PET scan. We also ordered genetic testing because he's high risk. Then, we have that imaging, I think, at this point to review. Let's pull it up.

Heather Jacene: I will start with the MRI of the pelvis. On the MRI, there was a 2.1-centimeter focal lesion in the left peripheral zone that was extending towards the apex and the base. On the DWI high B value, it was a high signal. This area had a low signal than on the T2 weighted image. There was also the suggestion of extra prosthetic extension over here. There were no lymph nodes seen on the MRI, and this was the only lesion that was reported as PI-RADS 5.

In addition, he had this bone scan, which showed the focal area of uptake at the right anterior ninth rib, which I'm circling here. No other metastatic disease was seen on the bone scan.

He also had a PSMA PET-CT scan, which showed the very intense PSMA uptake in the PI-RADS 5 lesion. You could also see that there was some extra prosthetic extension suggested. In addition to that single lesion on the left, there were also two additional focal areas of intense PSMA uptake on the right side of the gland as well as a little bit more inferiorly. There were no lymph nodes seen on the PSMA PET scan. Then, if you go up, and we scroll through the ribs... So this is 12, 11, 10, 9. This is the ninth anterior right anterior rib here. There was no PSMA uptake suggesting that it was, in fact, due to trauma.

Alicia Morgans: Great. Well, thank you so much for that, Heather. Let's start by talking about the MRI. Adam, what do you think about that?

Adam Kibel: I mean, that's a pretty striking finding. A lot of times, we see very subtle findings that the radiologist says is consistent with extraprostatic extension or is a button in the prosthetic capsule. But that looks like frank extension to me. I think it's really interesting that the PSMA scan backs that up. The question, when you're discussing a finding like that with the patient, is, number one, it's not a candidate for nerve sparing. Two, you have to discuss with them whether they're going to need adjuvant radiation therapy, either in the adjuvant setting or in the salvage setting, if you're following the PSA. I think it's really important to discuss it before you operate on them and very important they meet with the radiation oncologist so they can discuss whether they want that approach or where they want to go straight to radiation therapy.

Alicia Morgans: Yeah. I mean, Paul, to that end, what do you think about that, and especially with the new data from STAMPEDE, thinking about some of the high-risk features to which we might consider adding abiraterone for two years if we are using definitive therapy? What do you think about that, and how do you use MRI in that decision-making process?

Paul Nguyen: Yeah. Great, Alicia. I mean, of course, you're the expert on this topic, but I'm happy to add my two cents to it and how I think about it. This patient has Gleason 9 and evidence of extracapsular extraction on MRI. Technically, they meet the STAMPEDE criteria, where that trial included patients with either node-positive or any two out of three of, number one, Gleason 8-10, which he has, number two, T3, even by MRI, which she has. He meets the criteria. But number three was a PSA greater than 40. You could take two schools of thought here. One, you could say, well, this patient meets STAMPEDE criteria, and so they should get abiraterone because the stamped trial showed a survival benefit to the addition of abiraterone.

Another potential way to look at it is, does this patient look like the patients who are actually enrolled in the STAMPEDE trial? In that trial, about 40% of the patients were node positive. The median PSA turned out to be 38. What I often think about is, "Well, this is a patient with a PSA less than 10." Even though he does meet two out of the three STAMPEDE criteria that would technically have gotten him into the trial, he doesn't look like the other patients because his PSA is less than 10. Their PSA was 38 on average.

My leaning would be to be open about this patient. This is a patient who could potentially enroll on the NRG users 09 PREDICT-RT trial that looks at either intensification or de-intensification based on deciphers. The standard in that trial is radiation in 24 months of hormones without abiraterone. But I also recognize that some people might say, "Hey, this patient meets STAMPEDE criteria, even though he doesn't look like all the STAMPEDE patients. Maybe we should give him abiraterone." A lot to parse out there.

Alicia Morgans: Yeah. I didn't let you finish Adam's question or answering Adam's question. He really thought about and talked about the use of adjuvant radiation in this setting versus going to radiation right away. What do you think there?

Paul Nguyen: Yeah. I mean, with patients like this, I think I'm very open either way. I think that they could potentially have a good result with either approach. If I were to treat this patient we'd, of course, talk about hormone therapy and would talk with you about what you thought was the right duration. In terms of the radiation, I would typically treat the pelvis because we know that treating the pelvis improves outcomes in high-risk disease. I would treat the prostate, and then I would typically add a brachytherapy boost because we also know that can reduce biochemical recurrence by 50%. I would have to take that extracapsular extension into account. We can cover that with high dose-rate brachytherapy. We can sometimes even cover it with the brachytherapy seeds. I think either of those approaches is quite reasonable.

Adam Kibel: I think one of the things that's very interesting about this is we're starting to adapt to how we interpret a T3 disease on an MRI. Much of the clinical trial work was done on the bases of an abnormal rectal exam, not on the bases of an abnormal MRI. It's surprising how many patients have abnormal MRIs and a normal DRE. I'm still struggling to understand whether that's somebody who truly has what we used to call T3 disease, or is this an evolving pathologic criteria or radiologic/pathologic criteria that we need to figure out how to integrate into our pre-treatment decision-making.

Paul Nguyen: That's [inaudible 00:08:43]-

Adam Kibel: It's not as easy as we think it is.

Paul Nguyen: Yeah. I struggle with that, too, Adam, because, exactly as you say, all the trials, when they talk about T3, T4, that's all based on your finger. There are retrospective series looking at these patients that just have radiographic T3 versus real clinical T3. Their outcomes are way, way, way better than those patients that had clinical T3. I think we really have to think about whether it's really appropriate to apply some of that old trial data that was written for clinical T3s to these new patients with radiographic T3 that we now call clinical T3 based on the new staging system. I think that is definitely an area of controversy.

Alicia Morgans: I would agree. I think that's one of the reasons that I wanted to hear what you thought about the STAMPEDE data because I think that a fair number of the patients in STAMPEDE, if not most of them, were actually clinically T3 based on DRE rather than MRI. I think that this is something that I definitely am thinking about when I'm in clinic seeing these patients and trying to help them make decisions. It's easy if they seem to have lymph node-positive disease or if their PSA is over 40, but that's not the majority of patients that we end up seeing in clinic. It's really interesting.

Adam Kibel: One of the things is that we don't see this context here. The Gleason 9 cancer and the PSA and the abnormal MRI... They all add up. When you see things that are discordant, that is a little concerning. You see extraprostatic disease, and the patient has two cores of Gleason 6. I'm like, "There's something wrong here. One of them is not correct, and I'm not sure which is."

Alicia Morgans: That's when we have to really lean on our imaging. In this particular case, we leaned on the imaging with that questionable rib lesion, and Dr. Jacene, I'd love to hear your thoughts there. Ribs are tough, I think, in general. When it comes to PSMA PET, they can be false positives. In this case, we did not see that there was a positive rib lesion. But how do you think through that?

Heather Jacene: The first thing is looking at the level of intensity of the uptake that you see in the rib: if it's similar to what's going on in the prostate gland, to seeing that it's the same disease. The second is that this is a PET-CT scan, so using the information from both sets of images. A lot of times, these rib lesions... I think two common causes of false positives are these fibro-osseous lesions, which have a pretty typical lucency with the sclerotic rib. You can sometimes see that characteristic pattern or a fracture. I think it's a combination of all of those that can help you decide whether something really is truly a metastatic lesion or it's a false positive and then, of course, putting it into the whole clinical context with the chance that there is actually metastatic disease as well. I think it's a combination of all of those things together.

Alicia Morgans: Well, thank you for that. I think this patient... We've worked through his decision-making really, really well. Let's see what happened. It looks like this patient decided to pursue radical prostatectomy. I know that this was a shared decision. There are patients, of course, who come in with that preference. Despite that extraprostatic extension, this patient really felt strongly that was the direction that he wanted to go. He's going to have to make that decision about considering adjuvant or early salvage radiation potentially should he need it in the future. But time will tell. The prostatectomy is coming soon. Thank you for talking to sir, everyone.

Paul Nguyen: Thank you.

Adam Kibel: Pleasure.

Heather Jacene: Thank you.