PSMA

Tips from Nik Hanson: Basically a CliffsNotes on PSMA PET interpretation

I just finished a PSMA PET/CT and Theranostics conference. This is long, so I put it into bullet points, but I think it is invaluable if you are reading these studies and want to save yourself waffling about certain things and will give you the next step if there are questionable lesions and hopefully save you from missing disease by only looking a the PSMA activity as there is other important clinical information on these scan. This should be useful for people at Tumor Board who don't read these so you don't send people down the wrong road, or rec a biopsy in an inappropriate scenario. I wanted to share some salient points to help us be smarter than the people ordering the scans. Please note that we are using 2 different tracers at the office and the hospital and the scanners are VERY different so definitely pay attention when reading and comparing scans from different sites.

• Isolated rib lesion with activity below liver can essentially be ignored. If you call a met for this and there is no CT correlate, we won’t be able to biopsy and after this conference I have discovered that almost NO academic centers do rib biopsies for bony lesions unless there is a significant soft tissue component so we can safely say no to these low yield procedures. Often the CT will show a lucent lesion with rim sclerosis or other non-aggressive features. These can be followed if their SUV is not high (8+? There is no consensus or standardization on SUV)
• Perirectal nodes are definitely in the drainage pathway for prostate cancer as discovered as a result of this new technology and should be described.
• Contact of primary tumor to capsule for extra capsular extension. This will be hard to differentiate and probably over called by us at the hospital. It will be easier on the digi pet/ct. Basically if you can’t see a thin rim of normal uptake around a peripheral lesion in the gland, it is acceptable to raise concern for extra capsular extension. There may be microscopic disease which we can’t see and I think it can change the radiation treatment fields if Nancy Reyes asks about it. We can’t be definitive, but can raise the question and let her figure out how to treat.
• SUV > 9-19... Positive for prostate cancer almost universally in the context of these exams, even if in an isolated rib lesion. They will often do SBRT without a biopsy in this situation.
• SUV 2-8... Careful evaluation of the pattern of disease and suspicion for Mets (I won’t go into details about primary staging scans for high risk disease vs PSA return in a post prostatectomy patient, but these things matter)
• More bone positive lesions with F-18 tracers (mostly European and Australian experience, not as big a deal with pylarify) These are often inflammatory and can be a problem, again if it is SUV. 9+, I would call cancer/met. If it is 2-8 and an isolated lesion, you may have to hedge and can favor met vs degenerative change based upon presence of CT changes or not and clinical factors.
• SUV comparison across scanners and tracers is not valid for treatment response. We are using Gallium tracers at the office and F18 tracers at the hospital. Even with the same tracers, SUV calculations will vary based upon the scanners. If anyone asks if the SUV Max or Mean is clinically relevant I would just say that this question is still up for debate, but a single lesion that goes from 9 to 15 is meaningless at this point and especially so on different scanners.
• If FDG is hot and PSMA cold -> bad prognosis, not a good candidate for Pluvicto, this should be a rare case for us as we should probably not end up with FDG scans to compare unless the patient was initially staged before they knew the path. Neuroendocrine differentiated tumors and some aggressive pathology (cribriform and intra ductal variants can be low on PSMA expression and can have primarily lytic Mets)
• If you see PSMA positive disease (activity greater than liver visually) you MUST look for lesions that are PSMA negative as these will not respond well to Pluvicto. (THIS IS PROBABLY THE BIGGEST TAKE HOME POINT, PART OF THE VALUE OF THE STUDY IS IDENTIFYING PSMA NEGATIVE LESIONS AS THIS CAN CHANGE MANAGEMENT, ESPECIALLY IN THE LIVER/SOLID ORGANS) sorry to yell there
• Late stage disease, look for skull and brain Mets as these can be clinically significant.
• Look closely at solitary lung lesions, a more common than expected site of prostate Mets discovered as a result of this imaging study, probably need biopsy to differentiate met from second primary
• Inguinal LNs without deeper pelvic LNs are extremely uncommon site of nodal spread and should be looked at with a VERY skeptical eye.
• If you see obturator or int iliac or peri-rectal nodes, can probably assume the next group of nodes have microscopic disease that we can't resolve with even these sensitive exams. Important in case Nancy Reyes asks about treatment planning or a urologist is planning to be curative with a LN dissection.
• Lots of accessory salivary tissue anterior to parotid, around the pharynx. If no other site of disease, this can be essentially ignored.
• Visceral disease is more common than thought, and important prognostically. Mention any solid organ disease and whether or not it is similar in uptake to the primary disease (for primary metastatic work up in high risk disease where you see the lesion in the prostate is significantly advised for the tracer).
• Peritoneal disease is real, look for it! Thankfully it often responds well to systemic treatment.
• Degenerative change and inflammatory processes of bones can be positive.
• Meningiomas and fibro-osseous lesions can be hot. The CT scan often answers the met question. For meningiomas, contrast enhanced MRI should answer the question. Ribs are hard to evaluate (see above) Contrast MRI may also be useful for questionable bone Mets in long bones and spine/pelvis.
• Used for staging of high risk disease, pay attention to local extent of disease, they stage up if seminal vesicle involvement. Probably doesn't change the surgical plan, but important to note prognostically.
• https://recip-criteria.com/ is a training resource to make you understand this staging system. There are many staging systems right now. UCSF and UCLA are trying to create visual scores to save people from measuring anything (ie, low intermediate and high scales instead of measuring SUVs). There are free dosimetry programs and I will see if we can get them for us as they can segment and count all the SUVs for us if we become facile with using them. Great for tumor board and if we ever do trials they will be part of the reporting I am guessing.
• SPECT CT energy wings, probably not relevant to us clinically unless we start doing post treatment scan on a SPECT CT, ignore this for now.

I attached an article with the PROMISE 2 criterion if anyone is interested. I don’t know if this will be used in the future, but it helps clarify what the academics most current thinking is about these scans. We do not use liver directed tracers, so you can ignore those, and Pylarify is on the low end of the spectrum for artificial bone uptake when compared to the European and Australian tracers, but it still definitely has problematic bone uptake requiring a close look by us.

Thanks for your time, this was as short as I could make it and cover everything. As we all become more facile reading these scans, I think they will take less time than the average FDG PET, and given the rapid imaging time, they are great on our new Digi PET.