Gallium-68 PSMA Targeted PET Imaging in Prostate Cancer: Staging and Outcomes - Episode 4

Evaluating the Sensitivity of PSMA PET Scans

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Phillip Kuo, MD, PhD, reviews the sensitivity of PSMA (prostate-specific membrane antigen) PET (positron emission tomography) scans compared to conventional imaging.

Phillip Kuo, MD, PhD: I will take a moment to comment on the sensitivity of these PSMA [prostate-specific membrane antigen] PET [positron emission tomography] scans compared to conventional imaging. As you said, there have been multiple studies where they basically take patients for whom, by conventional imaging—particularly with regard to biochemical recurrence—they cannot find where the recurrence is at all. Then they do the PSMA PET. Essentially, you are starting at the baseline where the conventional imaging has failed to localize the recurrence. Depending on the patient population, sometimes they are finding sites of recurrence [at a rate of] around 50%, and there’s a wide range of course depending on your PSAs [prostate-specific antigen levels]. Again, this is a familiar concept, even going back to the bone scans, where the sensitivity of bone scans for localizing disease correlated with elevated PSA levels. You see the same, and we saw that with Axumin [fluciclovine] PET, where when you just had really low PSAs, first evidence of recurrence like 0.2, 0.3 [ng/mL] PSAs, it was pretty hard for Axumin to find those. When you get to PSAs of 2 [ng/mL] and above, the majority of the time, Axumin was doing a great job.

With these new PSMA PET agents, the sensitivity has come down so low that even with those serum PSAs of 0.2 to 0.3 [ng/mL], up to 20% to 30% of the time they are still finding the area of biochemical recurrence. And when we are getting up to the PSAs of 2, 3, 4 [ng/mL], in the vast majority of cases they are finding where the biochemical recurrence is occurring. I am so glad you talked about those skip areas. I have been fortunate to read hundreds and hundreds, probably close to thousands now, of these scans. That Virchow node, in particular, is of note; you start seeing that again and again, this tiny Virchow mode up there in the supraclavicular region, something that would never have been seen by CT or MRI or any other modality. You would never have suspected that that had prostate cancer in it. That is, for us, the most significant example of how this can just skip all the way up into the supraclavicular region.

It is a little depressing, honestly, as a nuclear medicine practitioner and radiologist, when you see the bone scans that look completely negative, and then you have a PSMA PET scan, and the patient isriddled with bone metastases. Really, it makes sense because the bone scan, again, relies on the reaction of the bone to the tumor. You have to have the tumor on the marrow start to grow enough to reach a significant size to destroy bone to see that reaction on the bone scan. Instead, with the PSMA, you are imaging the tumor because the PSMA molecule is overexpressed—over 100 times, in many cases of aggressive prostate cancers—and the target of the small molecule agents is on the extracellular surface of this transmembrane protein. It can bind there, and there is lot of this PSMA on these aggressive prostate cancers being expressed. We have, fortunately, a very good and specific target in PSMA for aggressive prostate cancers. I’m going to move to the next question….

Andre Abreu, MD: Can I make a point before you move to the other topic? With this, we’re now finding these different site of metastases—lung metastases, decimation, supraclavicular node metastases. Do you think we are discovering a new pattern, or there is hope for this, or a new way that the prostate cancer spreads that we did not know about before, just because we did not know what we did not know?

Phillip Kuo, MD, PhD: Absolutely.

Andre Abreu, MD: Is it a good assessment?

Phillip Kuo, MD, PhD: I think so. Research is still building on this. We caught a glimpse of it with Axumin. When I started the Axumin imaging, I was wondering whether I was right or not. It was similar to the FDG [fluorodeoxyglucose] PET scan days, where, when you first started looking at these FDG PET scans, you knew exactly where to look on that CT or on that MRI, and you just could not find a correlate, and so you hesitated. You would say, “Let’s just follow this up, because I’m not sure.” You needed that test over and over, and then you would get that follow-up from the tumor boards after months and months and years. Then you’d realize you’re right. Of course, you wouldn’t be right with 100% specificity, but you would be right a lot of times. We’re seeing this now. I’ve been fortunate enough to see follow-up serial PSMA PET scans as well to see how patients do without treatment and with treatment. It is useful to know you are right, that you are absolutely right. Now, I think it is going to change the paradigm of what we do, and you alluded to it I think, very poignantly, with the referral to oligometastatic disease. Our definition of oligometastatic disease has been faulty. We know it now—5 sites. That is by conventional imaging.

We know now, with a PSMA PET scan, that we can take that category of patients that we’d define as oligometastatic by conventional imaging, and we are going to find many more sites of disease. I think that is one of the most obvious examples of how this is going to revolutionize things. Honestly, we do not know yet, because what is going to be the new definition? That will be something that is going to require a lot of research because we need to tie that definition to prognosis and response to good treatments in the future, hopefully. Please, do you have any thoughts on that?

Andre Abreu, MD: I agree. Fortunately, what we see from the other side is that, we see new drugs coming more recently that again, from one side, we can better biopsy and diagnose these patients more accurately. Secondly, we are now able to better stage our patients and risk-stratify with several levels of stratification—genomics, imaging, markers, you name it. There is not only this, as now the treatment also has been changed over the years. It looks like the entire field is progressing, thankfully.

Phillip Kuo, MD, PhD: Another essential principle, when it comes to these intravenously administered nuclear medicine radiotheranostics, is that the lutetium 177 PSMA, when injected intravenously, will then go wherever blood goes and treat this metastatic disease everywhere in the body. If the metastasis has gone down to your leg and your femur, it will treat that. If it is up in your calvarium, it will go up to the top of your head. If it is in your liver, your lung, your lymph nodes—it is capable of treating every system, which is a very important contradistinction to, for example, external beam [radiation], where when you have a painful metastasis in your lumbar spine, they can spot-treat that with radiation, not only for pain relief but also for fracture prevention. But this treatment has the potential to treat every single tumor that’s PSMA-positive, and therefore be able to get ahead of the cancer, and not have to chase after it one at a time once it becomes symptomatic.

Transcript edited for clarity.