Prostate-specific membrane antigen PET: Who should undergo advanced imaging?
Dr Jérémie Calais - David Geffen School of Medicine UCLA, Los Angeles, USA
This morning I was asked to give a talk about PSMA PET-CT imaging for initial staging of prostate cancer. Basically with patients who have prostate cancer disease you need to know where is the disease before choosing a treatment and you have different imaging modalities. The one I was asked to talk about is a technique called PSMA PET-CT. PSMA means prostate specific membrane antigen, it’s a protein target that is overexpressed by prostate cancer cells, and you can do PET imaging of this protein expression showing where the prostate cancer lesions are. From that you can have many different indications and I reported all the diagnostic performance parameters and what are the potential indications for this imaging tool in that setting.
Primary staging you have a patient that has a prostate cancer, you need to know where is the disease – is it confined to the prostate or not? That’s the main indication. With high risk patients, based on PSA, T stage or Gleason score, these high risk patients have a high risk of having their prostate cancer being outside of the prostate, to have capsule ruptures or to be even outside of the prostate through having metastasis – pelvic nodes or even outside of the pelvis. So there PSMA PET imaging is very relevant because it can show with high accuracy, high sensitivity, these locations of metastasis. So usually you have a patient that would be known to have no metastasis based on conventional imaging, you would do the PSMA PET and you would discover new metastases somewhere else and it would change your treatment indication.
Now, this is new and, first of all, it’s not perfect. Sensitivity for pelvic nodal disease is about 40% so we still miss a part of the iceberg; we see only the visible parts of the iceberg in fact. What is also new is that we have to learn how to integrate these new findings into the treatment practice and the management. So before the patients that were known to be without any metastasis, now they have metastasis so how do we treat them? Do we treat them with metastases that were on another imaging modality before or do we continue to consider them M0? That’s new questions that the future will tell us how to do it. But, as of now, we have this new imaging technique that basically shows more disease than before.
You have a risk of overtreatment so from a radiation oncologist’s perspective, for example, you would see some lesions and you can expand your radiation field. You can do focal therapy on some additional lesions that were missed before. I think the toxicity profile is acceptable so even if you overtreat a little bit, you just treat the disease that you see, I don’t think it would impact in a major way the toxicity profile because they would do it in an acceptable way. Surgery, I think it goes the other way round. You exclude patients to get surgery because you know that the surgery will be unsuccessful.
Already, as of now, when you do surgery for prostate cancer half of the patients have recurrence after. But with this scan maybe we can see patients, this half of the patients, 50% of patients who are failing, maybe we can see them on the scan having some disease that was not suitable for surgery. Then you don’t do surgery on them. So you de-escalate the treatment, in fact, you’re not overtreating, you preclude surgery to the patient. By doing surgery to the patients that have no sign of disease outside of the prostate on the scan maybe you can reach a better success rate in this population. So for a surgical perspective it will not be overtreating, it will be to not do surgery. So it will be the other way around.
PSMA is the protein that is targeted. You have different PET compounds, so PET imaging compounds, that can bind specifically to this target. Some are free of use, so an academic site that has the physical capability to label this and inject it can do it. Many are owned by industry companies and worldwide you have a lot of the data has been generated with the ones that are free of use because any academic sites that have the facility to do it can do it and it’s more site independent. Now it’s very widely spread worldwide with this one but in the US, because it is considered as a drug because you inject it and regulated by the FDA as a drug, you need to do IND, NDA, this whole thing. There are not a lot of sites who can do this because an academic site would need to go to the FDA for having an IND, that’s complicated. Or it needs to be run by industry. So you have several players, companies, that are currently applying for either IND or NDA, there are different phases of FDA approval, but as of now there is no PSMA PET agent that is approved in the US. So it’s very used worldwide in many research sites and you have tonnes of patients that have a scan with that but in the US, as of today, it’s not approved, it’s still research.
Do you think it should be standard practice in the future?
Yes. Like I said, there are several players that are already in connection with the FDA for an NDA, so new drug application approval of a drug. Different stages of advancement. I would say that maybe by the end of 2020 or maybe early 2021 there will be at least one PSMA PET agent approved in the US.
Are there any other advantages?
It’s a more sensitive technique, imaging technique, than the current standard ones. Now, how to act on these findings, this is another question but that’s the main advantage. You see more disease than before, than you can imaging many potential applications. For example, for primary staging you have patients you know probably they have prostate cancer because you have, for example, elevated PSA. You want to have the diagnostic, you need to do a biopsy in the prostate but for some reason all the biopsies you do are negative. Or you do an MRI and the MRI is equivocal or negative but you really think the patient has prostate cancer. Then you could do a PSMA scan showing where this significant cancer focus is to make the diagnostic, target your biopsy and have some tissue out.
And you can even think further. For example, you do PSA screening, it’s a blood test that detects the PSA that is produced by the prostate and the prostate cancer cells. The whole thing is to know which is cancer or not and in the cancer which are the ones that you need to treat and act on. Because you have some that are very low grade, not indolent but very slowly evolving – you don’t necessarily need to do something on it. It has been shown that the signal that you see in the PSMA PET is correlated with the grade and the aggressiveness of the disease and so maybe you can make the difference between patients who have no disease, that you don’t see anything in the prostate, so just doing active surveillance would be acceptable because either they don’t have disease or it’s only low grade, not aggressive. And when you see an intense signal this means we are using it to biopsy and it means you need to treat this disease. So a more individualised treatment approach.
I think as long as you have this available you should order a PSMA PET scan for every high risk patient that is coming at primary staging. And also if a biopsy or MRI are negative and you suspect that your patient has prostate cancer. That’s the main take home message.