Alicia Morgans: Hi. My name is Alicia Morgans. 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: Good 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: Hi. 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. For our next case, patient GG. Mr. GG is a 69-year-old man with a history of Crohn's disease that's under control, arthritis, chronic HCV, hypertension, and non-muscle-invasive bladder cancer. He's retired and spends time riding his Harley with his wife. He did have a really traumatic crash about 15 years ago where he and his wife were riding together on the Harley and ended up with a collapsed rib and some hospital time related to that particular crash. In terms of his prostate cancer, in March of 2019, his PSA was 13.6. By May of 2019, his PSA had gone up to 15.79. He really didn't do anything in the immediate timeframe there. I think the pandemic may have had something to do with that, but in December of 2021, his PSA went up to 16.21. December, he had a prostate biopsy that was notable for Gleason 3+4=7, grade group 2 prostate adenocarcinoma, and three cores on the right and there were six cores that were negative in the biopsy specimen.

In January, he had a CT abdomen and pelvis that was negative for metastatic disease, but had focal thickening in the bladder wall, likely secondary to a recent TURBT that he had undergone. He also had a bone scan that was notable for focal increased radiotracer in the posterior ninth rib without correlating lesion on the CT on the outside. This was indeterminate. He had all of that work done on the outside and then he came for a second opinion and saw medical oncology. His imaging was reviewed, all of the reports and the scans. We ordered some additional tests. In March of 2022, he had an MRI of the prostate that showed a PI-RADS 4 lesion with no ECE and no pelvic lymphadenopathy. We're going to review. I also ordered a CT chest that we were going to have Dr. Jacene talk us through. Then just other information. At that time, we had a PSA of 24.33. This has gone up and he also had a PSMA PET scan. Dr. Jacene, can you talk us through the prostate MRI?

Heather Jacene: Sure. This is the left of the screen on the ADC. There was an area of hypointensity that again, correlated to an area of hyperintensity on the DWI images. This was consistent with the PI-RADS 4 lesion. Then on the repeat CT scan of the chest that he had, we can actually see on the axial images in the right ninth rib, there was an area that looked sclerotic compared to the other ribs where the red arrow is. But importantly, when you look at this on the sagittal views, you can see that there's the lesion besides the sclerosis, there's really a lucency and that the sclerosis is around the lucency. This is a very typical pattern of this ring and arc sclerosis, which you can see in benign fibro-osseous lesions on a CT scan. So based on the appearance here, it looks like it certainly doesn't look like a fracture. There's no line with healing, but it does have a typical appearance of a benign fibro-osseous lesion on the CT.

Then he was referred for a PSMA PET scan. He had a PSMA scan ordered and this is the scan. If we start down in the prostate bed, we can see that there's focal intense PSMA uptake that was correlating very nicely to the lesion that was seen on the MRI. We didn't see any lymph nodes in the pelvis or the abdomen. Then when you specifically go back up and look at the ribs, let me change this to a bone window. As we come inferiorly to the ninth rib, on the CT, again you can see the area of sclerosis around that lucency. This is a little tricky because it's right next to the liver, but if you look at the fused image here, there's really no PSMA uptake that is associated with this sclerotic lesion. So now the combination of the CT pattern of the sclerosis and lucency with the sclerotic rim and the lack of PSMA uptake is very reassuring that this is not a metastatic bone lesion and that this disease is localized to the prostate gland.

These fibro-osseous rib lesions are quite common. They can happen post-traumatic and they're very common and you can see them and you can also see them. They sometimes do have mild PSMA uptake and they can also be seen on a bone scan as well.

Paul Nguyen: Can I ask you a related question, which is that I've heard that sometimes on a PSMA scan, you can have a false positive for a single rib lesion?

Heather Jacene: Yes.

Paul Nguyen: So is it sort of the converse of this almost?

Heather Jacene: Well, I think sometimes these lesions can have a little bit of PSMA uptake and so these lesions have a spectrum of uptake. They're typically not as intense as what you might see in a prostate cancer lesion, but it can have mild uptake and these are often false positives, but also fractures can have increased PSMA uptake. It's really a developing laundry list of things that can have PSMA uptake that is not prostate cancer. It's really the entire picture of the patient's picture, the CT finding, and the PSMA that should help in the interpretation, all of that information. Just because it has PSMA uptake, it might be prostate cancer, but you have to think about other things and whether it makes sense in that patient at that time that it does represent metastatic disease.

Adam Kibel: Heather, that raises the point. Are there other locations in the body where this seems to go too frequently? I've seen in my experience, they go to the thyroid quite frequently and I seem to have some of our endocrinologists on speed dial now because of PSMA PET. Do you want to comment on the risk of finding true malignancies, but also false positives in thyroid gland?

Heather Jacene: Sure. Thyroid neoplasms can have PSMA uptake. The thyroid, it's very vascular and you can have PSMA on neovasculature. If you see something that's focal and intense in the thyroid, that's a higher risk for thyroid malignancy. There are also other tumor types, I think, that's probably less common than seen in the thyroid glands or not something focal in the thyroid glands. I think the other things that are commonly false positive that's particularly challenging are the celiac ganglion or also presacral ganglion that can have PSMA uptake and you don't want to mistake those for lymph nodes, because usually, there's a little soft tissue that's associated with those that can be a false positive as well.

Alicia Morgans: Great. Do you have tips for clinicians as they're newly using PSMA PET? Is there anything about a rib lesion that you would say that's more likely to be metastatic disease versus that's not? I know you talked about the big picture, but is there anything that you would just throw out as a clinical pearl or a tip?

Heather Jacene: I would say if you could find old images to see if something was there in the past, that's one thing that can be very helpful, the patient's history for any trauma. Then also when you're looking back at old scans, things that are benign, I think, tend to have been there for a longer time, but things that are changing, then that's more often can be metastatic disease. Then if something doesn't make sense, to reach out to the radiologist who read it to maybe explain why it doesn't make sense and to think through together what other lesions it could possibly be than prostate cancer and come up with a plan.

Alicia Morgans: Absolutely. In this particular case, you humored me quite nicely and I really appreciated it. We walked through that CT from the outside hospital with the ribs and it was a little bit difficult to even capture that area. I think that was an active in pelvis, so this was the lower part. Then you talked me through this sclerosis with this area of lucency around it and it was very, very reassuring. Then of course, we had the PSMA PET scan that also reiterated that this is going to be a negative lesion, which in general, it was very reassuring for me. It was very, very reassuring for the patient, so thank you for that. Let's move on to his treatment. Mr. GG decided to move forward with radiation and ADT for two years. Remember his PSA actually increased over the time that we saw him from less than 20 to greater than 20, which was one of the other reasons I was nervous about this possible rib lesion, but that also is what pushed him into a high-risk setting where he did get two or is getting two years of ADT.

We decided not to intensify with abiraterone acetate due to the STAMPEDE trial data suggesting that that could be beneficial in terms of prolonging survival for patients with very high risk disease because he didn't have clinical lymph node positive disease. He didn't have metastatic disease because we had a negative imaging with that PSMA PET. His PSA was less than 40. He only had Gleason 3+4 disease, so didn't meet criteria by Gleason score either. So really, did not meet those criteria for that in additional intensification. He's doing well. We appreciate that and thank you guys for talking this through.