Clinical Utility of PSMA Imaging in the Initial Staging and Use in Surgical Planning: Part 1

By David Ambinder, MD - Last Updated: September 27, 2022

Dr. David Ambinder: We have with us, Dr. Sprenkle, we appreciate your time and we’re excited to hear what you have to say. Dr. Sprenkle is an Associate Professor of Urology at Yale as well as the Chief of Urology at the VA up in Connecticut and he also is Vice Chair for the NCCN Early Detection of Prostate Cancer Guidelines. So, this is really exciting to talk about some of the topics that come up with PSMA and the evolving landscape of PSMA. My name is David Ambinder. I’m a Urology Resident at Westchester Medical Center in New York. Anyway, going forward, so I’ll ask you the first question, we’ll just take it from there. But for our listeners and for our viewers, can you describe for us PSMA and why PSMA PET imaging is so effective and has become so popular so quickly?

Dr. Preston Sprenkle: Sure. Well, I’ll try. PSMA, it’s a very interesting marker. So, it’s present in prostate tissue at low levels and throughout the body, and PSMA imaging actually initially started many years ago with the ProstaScint® scan and it did detect prostate cancer but it was not real specific for prostate cancer and detected prostate tissue as well and it didn’t really gain a lot of favor so it was used intermittently.

Prior to that, is probably because of cross sectional imaging and limitations there. I actually don’t know all of the history. But recently, the PSMA imaging that we’ve been using with the specific molecules and markers and antibodies that we have now, is much more specific for prostate cancer. And so it has a much higher signal in especially high risk and metastatic prostate cancer than with surrounding prostate tissue. And the relatively recent rapid growth of the use of PSMA is because we have a lot more facility with PET CT. I think that’s one of the main reasons. I am not a radiologist, I’m a urologist, so we use these tests, but I think the great interest is because we have been able to now complete trials that show that PSMA based imaging is superior to what we’ve been using for 20 years and that’s really I think why we’re getting a lot more interest.

Dr. Ambinder: And currently, what are the indications for obtaining PSMA imaging?

Dr. Sprenkle: So, PSMA imaging right now, the indications are evaluating for metastatic prostate cancer. It is FDA-approved for both in the initial staging setting, so men who are at risk for having metastatic disease and also in the evaluation for metastasis in the recurrence setting, so in someone who’s been treated for prostate cancer, but we’re concerned they may have a recurrence based on rising PSA levels.

Dr. Ambinder: Got it. And you mentioned earlier that it’s largely been shown to be superior in many studies over what we’ve had for the last 20 years, and I know outside of an academic center for many years, it’s been bone scan and the CT scan that was the… And I know that at certain institutions, they had certain other tests, axumin scan, choline based, or fluorine-based tests. If you can tell us why PSMA is superior to those imaging modalities?

Dr. Sprenkle: Sure. So, many of those other imaging agents, so 11C choline, the sodium fluoride PET, axumin scan, those are all superior to being what we consider the conventional imaging which is CAT scan and bone scan. And there have, I don’t know think I’ve seen it published, but I’ve seen it presented some comparisons of 11C imaging, axumin, PSMA PET and they pick up different things and so they all are superior to typical CAT scan or bone scans. But in terms of axumin versus PSMA PET, I mean, one of the main limitations or how accessible or available are these other scans. And so 11C choline, that’s a really specialized test. That’s only available at a few centers like in the US around the country.

And the sodium fluoride pet that became very… We used that a lot, but it was so sensitive that there were potentially some false positives and so while that was better than a standard bone scan, we would use it in men who we were really evaluating, but you worried about false positives and how you would evaluate that. With axumin, it was approved and it was available for many of these PSMA PET CT imaging studies were available. It was approved I believe in 2016 and it was definitely superior to CAT scan and bone scan, but it was only approved in a setting of if the host tests were abnormal or in the setting of biochemical recurrence. So, you had to… The approval was there, but it wasn’t as easy to use. So, it was a real breakthrough when the Gallium PSMA PET was first approved, I believe in early 2020 because it was approved at that time for all staging.

And in the subsequent comparative studies, we see a significant improvement in sensitivity and specificity with PSMA based PET over conventional imaging which is bone scan and CAT scan. So, it detects more cancer and what it detects is more likely to be cancer than what we found in those other studies. And in a sense, and it makes a lot of sense, because PSMA based imaging, it is targeting cells. So, it is looking for things that look like prostate cancer, whereas bone scan and CAT scan are looking for morphological changes. So, just changes in the bone that could be anything we’re presuming it’s prostate cancer because someone has prostate cancer. And similarly in the lymph nodes, someone has an enlarged lymph node, but we don’t know if that’s inflammation, we don’t know if that’s prostate cancer. So, using a prostate cancer-targeted antibody is going to be much more accurate and that’s definitely what we’ve seen in the clinical trials.

Dr. Ambinder: That’s fantastic.  And that leads me to my next question and it’s been a few weeks since I looked at the NCCN guidelines, but all throughout the NCCN guidelines is footnotes of whether PSMA can replace or should it be done in addition to or separate. Are we ready to say that PSMA imaging completely can replace conventional technetium 99 bone scan?

Dr. Sprenkle: So, the according to the footnotes in the NCCN prostate cancer management guidelines, yes. They suggest that definitely can be considered as a replacement. I think the reasons for that are, as I mentioned before, it does appear to have better sensitivity and specificity, it’s one scan instead of two. There are even some studies that show there’s a significantly reduced dose of radiation by doing a PET CT versus doing both the CAT scan and the PET CT, so it’s almost half of the radiation dose that you get. So, there are a few different things that make it superior. Unfortunately, many insurance companies seem to be lagging behind. Medicare has approved it, but that’s a struggle that we have.

I know many other centers that are at the cutting edge of this type of imaging are having is where we’re getting a lot of denials and having to do a lot of appeals. I think it’s largely because the companies recognize that this is coming, but they’re trying to put the brakes on as much as they can. They consider it investigational, I’m not sure what else. The FDA has approved it. There are growing number of studies so we will probably reach that threshold sometimes soon where we’ll see more blanket approval and coverage with insurance.

Dr. Ambinder: We’re seeing that similarly at our center as well, more denials and approvals.

Dr. Sprenkle: But I think specifically to answer your question over bone scan, yes. There is an improved identification of metastases and there can be some false positive. The overall average false positive rate is lower with PSMA based imaging than with CAT scan or with bone scan. But we still do see those. One of the ones that jumps out often is an isolated rib metastasis. Those seem to happen a little more frequently than other type of false positives so we just need to be aware of that. But the false positives seem to be reproducible so there are things that we can look at especially with a well-trained nuclear medicine, radiologist who’s versed in PSMA imaging, they kind of know what those are and can identify them.

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