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PSMA stands for Prostate Specific Membrane Antigen, which is a protein (enzyme) that is expressed on the surface of prostate cancer cells (and on a few other cell types). As with many cell surface proteins, you can find ligands that will bind to the protein, and then label these with radioactive isotopes that allow imaging. PET stands for Positron Emission Tomography, and of course, CT stands for Computerized Tomography. When you put these technologies together, you obtain a powerful way to look for prostate cancer that has spread outside the prostate gland. The physics of this (how a positron interacts with an electron, releasing gamma photons at 180 degrees) is very cool, but probably of interest only to the most nerdy. (I made a cloud chamber for my 7th grade science project and my hiking buddy is a nuclear medicine doc who wrote a definitive text on the math/science of his craft…so go figure).
Prior to developing PET agents for prostate cancer, we had standard CT scans and bone scans and we used these to determine whether someone with, for example, a very high PSA or high Gleason score had cancer deposits that had escaped (metastasized) from the prostate. If so, it was felt that putting them through surgery or radiation treatments in an attempt to cure was fruitless and exposed the patient to the unnecessary toxicity risks (impotence, incontinence, rectal damage, etc.) Especially if they had symptoms (e.g. bone pain), hormone treatment reducing testosterone was the best approach. If you had a rising PSA several years after local treatment, the question was always, “Where is the cancer?” but the sensitivity of routine bone and CT scans was quite limited not showing anything until the PSA reached 10 or so at which time ~1/2 of scans would be positive. 
This figure illustrates the difference in sensitivity. A normal sized lymph node on CT scan (left) is revealed to contain prostate cancer with the PET isotope technique (right). At present, the only approved PET scan in the U.S. is fluciclovine, the “Axumin” scan, which the FDA approved for detecting cancer in patients with rising PSA, but not in newly diagnosed patients. In several studies PSMA-PET CT scans are even more sensitive (about 3x) than Axumin. At the risk of calling up an overused phrase, “this changes everything”.
First, it is clear that many high risk patients we would previously have treated with surgery or radiation to the prostate hoping to cure them might now be found to have prostate cancer deposits outside of the treatment target (prostate or prostate + pelvic lymph nodes). A superb study in this month’s Lancet found that PSMA PET-CT scans provided higher sensitivity (85% vs 38%) and specificity (98% vs 91%) than routine bone and CT scans in high risk patients (PSA >20, Gleason 4+3 or worse). Does this mean we shouldn’t treat the prostate in high risk patients with positive scans? In the study, conventional imaging changed the management in 15% of men, while PSMA PET-CT imaging changed the plans in 28% (p=0.008). Should all high risk patients have a PSMA PET-CT before deciding on treatment? Should the FDA approve this scan quickly? (It is currently available only in research centers and not covered by insurance…read my blog on how to search for such studies or click here).
Second, what about treating a small number of prostate metastases (oligometastatic prostate cancer) in a patient who was treated years ago and now has a rising PSA? Ongoing investigations suggest this might delay the need for hormone therapy in such patients or potentially even cure some of them. But the PSMA PET-CT isn’t perfect. How high do you let the PSA go up before ordering such a scan? – the farther it rises, the more likely the scan will show something, but that gives the cancer more time to spread. A negative scan is no guarantee there aren’t many more foci of a few prostate cancer cells that will eventually show up elsewhere in the body. Is this some version of Whack-a-mole? And how do we define “cure” anyway?? (My personal definition is that you die from something else, regardless of your PSA or scan results).
Finally, since even at research centers the PSMA PET-CT scan may cost you $3,000 or so, is it worth it? It is “free” in the European health care systems, but we all know nothing is free – even if Medicare pays for something it costs society and ultimately must be accounted for in terms of value. Medicare covered PSMA PET-CT’s vs fixing pot holes and bridges? How about finding a treatment for SARS Co-V2 instead? No easy answers, but if you are like me, homebound as a “high risk” senior citizen, plenty to think about. Wash your hands, wear your mask, and enjoy your grandkids on Zoom!
prost8blog 
Hi Dr. Glode, A great explanation. However, you didn’t reference choline scans or psma Theranostics. With choline scans, my husband (Gleason 10 for 11 years) was able to have SBRT at Mayo for oligometastases allowing him to stay off ADT for years. This year, with a psa of 16 in January, and doubling time of two months, he had psma Lutetium treatments in England and Australia. His psa has dropped from 16 to 0.5 with no ADT or other treatment. We live in Colorado and Bill is a former patient of yours. We so appreciate the advice we received from you and your prost8blog. Thank you so much. Cindy Landsberg
Hi Cindy, Hello from Ft. Collins. Not sure if you’ll get this reply, but my family would be interested in talking with you and your husband about your experience. My dad has had Gleason 9 cancer for 5 years and recently finished SBRT treatment following PSMA findings of metastasis and a rapidly doubling psa (which continued to climb following sbrt). He has been through chemo previously and has been on ADT continuously. Now he is back on round 4/6 of chemo and we’re not sure it’s going to be effective.
We would like to ask you about the Lutetium treatments if we could. My phone number (call or text) is (nine-seven-zilch) three-nine-1-zilch-five-seven-three.
We are also so grateful for Dr. Glode and his team that continues the good work at UCHealth but would love to talk to someone who has gone on to the next step after SBRT.
Mike, A very good article. It might be good to mention FDG PET/CT which many of us are getting and what it’s limitations are.
Bob
I linked to the VISION trial here: https://prost8blog.com/2020/02/26/new-findings-from-clinical-trials-2020/
You can also see ongoing trials with Lu177 here: https://www.clinicaltrials.gov/ct2/results?recrs=ab&cond=Prostate+Cancer&term=Lu177&cntry=&state=&city=&dist=
Hi Cindy,
Glad you brought in those additional aspects of using PSMA as a target for imaging AND therapy. There is only so much I can cover under one heading without getting too verbose, but your comments are spot on. Very glad Bill is able to take advantage of the novel advances. Best wishes! MG
Dr. Globe,
I just received my prostate biopsy results (positive in 6 of 12 cores, Gleason 4+4 in 3), following PSA going from 1.55 to 17.8 over the last year and then to 19.4 4-5 weeks later. Would you recommend getting a PSMA-PET for a new diagnosis before commencing with any treatment?
I was referred to you and your blog by family members, and would like to have the opportunity to talk with you before proceeding with treatment, but am reluctant to call you on the Saturday after Thanksgiving. Please let me know if there is a date/time that would be convenient to contact you.
Best regards,
Ron
Best to contact me through my work: (970) 569-7429. I try not to answer specific questions on this blog due to medical legal reasons. Tell the staff to have me call you.
Thanks Bob,
FDG PET was essentially the first of the PET scanning techniques. F luorine 18 is the positron emitting isotope and D oxy G lucose is the biologic that is taken up by cancer cells. Many cancers rely primarily on glucose for metabolism (Warburg effect) making this an excellent scan for lung, breast, lymphoma and several other tumors. Prostate cancer relies more on lipid metabolism and FDG PET doesn’t work as well…or when it does work, it may indicate that the cancer is becoming a more aggressive subtype. However FDG PET scans are widely available and thus often ordered by oncologists.
Hello from Sweden! This part confused me a little:
”Second, what about treating a small number of prostate metastases (oligometastatic prostate cancer) in a patient who was treated years ago and now has a rising PSA? Ongoing investigations suggest this might delay the need for hormone therapy in such patients or potentially even cure some of them.”
Cure some of them? Would love to know more?
Also what are your thoughts regarding Naf-PET-scans? We use then in Europe.
Some of this comes down to the definition of “cure”. Take a look at the STOMP trial: https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.6_suppl.10
If you die from something else, can we say you were cured? Many of the studies seem to indicate that this approach is useful and it is becoming more popular with the advent of the more sensitive scans as you imply. NaF-PET is more sensitive for bone mets than routine bone scans, and PSMA-PET scans out-perform standard CT and bone scans as well as fluciclovine. (Axumin). There is a growing literature on the topic here: https://scholar.google.com/scholar?as_ylo=2019&q=oligometastatic+prostate+cancer&hl=en&as_sdt=0,6
Hope that helps. Fad or advance? May depend on one’s perspective (and pocketbook…)
Thank you very much! A follow up question: as I’m reading the litterature on oligometastic PC and high gleason score I understand that everyone is arguing for different approaches: either more aggressive from the start with chemo + ADL, while other suggest that you can ”cure” (perhaps with the definition ”dying from something else”) with only extensive radiation. What are your personal views regarding this?
Generally “more is better”, but “more is also more toxic”. There are definitely limits to how much can be gained by increasing treatment intensity, and in some cases, the addition of logical intensification strategies (for example increasing the radiation dose, or adding more than one second generation ADT agent or chemotherapy) simply adds toxicity without any demonstrable benefit. That’s why its best to enter clinical trials whenever possible to answer these kinds of questions.
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