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 urinary 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 and Women's hospital. Excited to be here today.

Alicia Morgans:  Wonderful. Let's move on to patient RG. Mr. RG is a 66 year old man with a history of hypertension and hypercholesterolemia. He's an electrical engineer, and remains active at work and at home, and enjoys visiting his grandchildren. In January of this year, his PSA was 4.86, and at that time he underwent a CT abdomen and pelvis that showed an enlarged prostate and bilateral renal cysts that were not concerning. In February, he underwent a prostate biopsy that showed Gleason four plus three equals seven, grade group three in three cores on the right, and Gleason three plus four equals seven grade group two in four cores on the right, with perineural invasion.

In March, he had a bone scan that showed a mild uptake in the right frontal and left temporal-occipital calvarium that was concerning for possible metastatic disease. In March, he underwent an MRI of the prostate that showed a PI-RADS four lesion on the right, with a focal area of probable ECE. He was referred for a second opinion, and his imaging was reviewed. At that time, an MRI of the brain was ordered, and a PSMA-PET was ordered. The MRI of the brain was ordered at the recommendation of the outside hospital team that had read the bone scan. He also underwent genetic testing, and was found to have an MLH1 pathogenic mutation. His case was reviewed in tumor board. Let's review some of his imaging. Heather, can you walk us through the prostate MRI?

Heather Jacene:  Sure. On the left of the screen is the ADC image, where you can see the red arrow is point pointing to this hypo intense area on the MR. On the DWI image, this correlates to a hyper enhancing lesion, which was consistent with the PI-RADS four lesion that it was red as.

On his bone scan, we can see in the right frontal bone, there was an area of mildly increased radio tracer uptake, and there was a second lesion that was in the left temporal bone. These were both further evaluated by the brain MRI, which was recommended. There was an area of enhancement in the right frontal bone, which likely correlated to the area of the abnormal uptake on the bone scan. However, it was still nonspecific, and on the brain MR, the left temporal lesion was not seen. Given that non specificity of the findings on the brain MR, a PSMA-PET scan was recommended for a further evaluation.

Paul Nguyen: Heather, can I ask, how concerning was that bone scan, just based on the bone scan alone? Just looking at the case, I would've thought, "Okay, this is someone with intermediate risk. The PSA is pretty low. It's just a few cores of Gleason four plus three, and a PSA of well less than 10." If the bone scan wasn't that concerning, I might've just presume that it wasn't much to look at.

Heather Jacene: That would've been fair. We often see these benign things in the skull, not uncommonly. I think they're just non-specific, and I think more often than not, they're not followed up with an MRI or anything, unless you see other lesions elsewhere.

The PSMA scan was ordered, which showed the lesion that was correlating to the findings on the MRI, on the PSMA scan. There was intense PSMA uptake, really diffusely throughout the prostate gland. The PSMA uptake was more extensive, I think, than what was actually seen on the MRI. We didn't see any abnormal lymph nodes in this patient. When you look specifically at the skull region, it was, again, a little bit more of a marrow based lesion, so there were not a lot of CT findings. But, as you scroll through the skull, there was really no abnormal PSMA uptake in the skull at all. Given the intensity of the uptake in the primary tumor, typically the metastasis are, at least early in the disease, similar levels of uptake. Given the discrepancy, this would argue against the skull lesion being a metastatic lesion, and that the disease was localized to the prostate gland.

Alicia Morgans: Thank you for going through that with us, Heather. Adam, we'll start with you. Again, this patient really wanted surgery, and obviously, we would not want to send somebody for surgery, outside of a clinical trial, if we thought that they had a metastatic disease to the skull. What are your thoughts on this particular patient, and the imaging findings that we have?

Adam Kibel: This patient, at the current time, we can't demonstrate metastatic disease. I think the PSMA-PET was very useful in defining that the patient doesn't have metastatic disease. We tend often to think about these tests as proving that patients do have it, but they can be useful on the other side, by demonstrating that they don't. My inclination would be to offer this healthy 66 year old with unfavorable, intermediate risk prostate cancer a prostatectomy. The MRI findings would be concerning, that we would need to go wider on one side, in order to make sure we had a negative margin. I would clearly review the MRI with radiology, in order to ensure that we were making the right choice, in terms of how close and what sort of nerve sparing we could do.

I would clearly discuss with the patient the possibility that they might need a salvage radiation therapy after the surgery, if their PSA started to climb. They're certainly not the kind of patient where you can look them in the eye and say, "Look, I'm going to cure you with surgery." I don't think you can say that to anybody, but certainly, this is one where you're concerned that they could have a recurrence. I would have absolutely no problem operating on it.

Alicia Morgans: Thank you for that. Paul, this is a general question, not necessarily about this patient, but in my practice, an area that's particularly difficult to biopsy is the skull, I'm not sure what your thoughts are. Ideally, we would have tissue to say, "We don't have any evidence of metastatic disease," but a negative biopsy does not necessarily mean there's not cancer there, it may mean that you just haven't gotten it. I feel, actually, quite comfortable with this type of an approach, not biopsying the patient, and having a negative PSMA-PET, and using that to help justify that there's no metastatic disease. I'd love to hear your thought. How do you make the choice?

Paul Nguyen: Yeah, I think very much the same way about these kinds of situations. I do find that bone biopsies, when they're positive, it's great, and it tells you something, but when they're negative, it doesn't actually reassure you as much as you'd like it to. I think that the PSMA is a wonderful tool, especially in this setting that we just saw, to give us a lot of confidence that it wasn't real, because if we saw that much on a bone scan, and we think that it is real, I would expect to see it on the PSMA. I think that we can also go back to first principles. This is a patient with a PSA of 4.8, a few cores of Gleason four plus three, so most likely, that wasn't real. The fact that the PSMA confirms that, I think, gives me a high degree of confidence that we don't have to worry about metastatic disease.

Adam Kibel: Heather, I struggle a little bit with the negative path. I've read the Osprey trial, and it's got a sensitivity of 40%. When you look at lymph nodes, it maybe improves a little bit, if you increase the size of lymph nodes to greater than five millimeters. What's the sensitivity and specificity for boney metastatic disease. Do we have any data on that?

Heather Jacene: Yes, that's a great question Adam. Within the Osprey trial, there were two cohorts of patients. The first was the cohort A, which was the initial disease, looking for the local disease and the pelvic nodes. In that setting, you're right, the sensitivity was 31% to 42%. The negative predictive value was 815 to 84%. When you look at cohort B, which was the metastatic cohort, where they would biopsy more of the metastatic lesions, including the bones, the sensitivity was 93% to 99%, and the positive predictive value was 81% to 88%, meaning if the PET was positive, it was very likely that there was prostate cancer there. The challenge is still with the negative PET, because they didn't biopsy any of those negative lesions, to really find out the true negative, predictive value of the test for the bone lesions. I think that's still an answer that we don't have definitive data for.

Adam Kibel:  Thank you.

Alicia Morgans: Thank you. I think, at the end of the day, it's really just going to be a decision for some of these patients, but it is nice to have this information, to support that decision making. Let's see what the patient did. For this patient, he decided to move forward with radical prostatectomy. This is planned for June of this year. He was really grateful to be able to move forward with a modality that did not involve any hormonal treatment. Also, very interested to learn that those bone scan lesions might have been something that he's retained since childhood. He could really talk to his sisters about some of the games they used to play, and some of the knocks that he took on his head when he was younger. Hopefully, all will go well for him, with surgery. Thank you guys for talking this through.

Paul Nguyen: Thank you.

Adam Kibel: Thank you, it's a pleasure.

Heather Jacene: Thank you.