Imaging With Fluciclovine for Prostate Cancer - Bital Savir-Baruch
March 17, 2021
Bital Savir-Baruch, MD, Assistant Professor, Department of Radiology, Loyola University Medical Center Maywood, Illinois
Bital Savir-Baruch: Hi everybody. Thank you very much for joining our session speaking about fluciclovine images. I am Bital Savir-Baruch, I'm a nuclear medicine physician from Loyola University Medical Center at Maywood, Illinois. This session will be part of a series of lectures organized by the Society of Nuclear Medicine and Molecular Imaging, speaking about prostate cancer diagnosis and treatment. My session will cover briefly imaging with fluciclovine PET CT scan. We will cover in this session the limitation of conventional imaging for localizing prostate cancer sites in patients with suspected disease recurrence. The second part of this presentation will cover the role of fluciclovine PET CT imaging in prostate cancer recurrence.
Now, before I go really into the topic of today of fluciclovine, I would like to try to explain what's the differences between conventional images and molecular images. So if you look at the left side, conventional images are usually referred to as CT and MRI, which means that by using magnetic fields or x-rays, we can actually create really nice and detailed images of our anatomy. And then we take that anatomy compared to what we know and we are trying to look for sites that are showing abnormal areas by size, by shape, and by location.
On the other hand, when we look at molecular imaging, we're looking at biological pathways. And what does that mean? It means that we are using either photons or single-photon emission to identify abnormal pathways, abnormal biological pathways, for example, overexpression of receptors or some overuse of different pathways that are being done in the body. And on the right side, you can actually see that there is a very blurry image, but that blurry image can actually be fused to the detailed anatomy images and actually can localize areas of abnormal pathways, which is really, really a different approach that we are adopting with time.
So going forward into fluciclovine, also known as FACBC. Fluciclovine in fact, it's an amino acid. Now in our body, we are using amino acids for building proteins in a normal way. Now the body thinks we are giving it amino acid to use to build those proteins, but in fact, we're not. Amino acid that we're giving the patient under the name of FACBC and fluciclovine is actually a synthetic compound. So the body will take it, think it can use it, but it's not going to happen because we are preventing that process.
Now why it becomes so important in prostate cancer cells, because prostate cancer cells tend to use amino acid much more than regular cells. So on the right side, you can see that those amino acid transporters look like an ATAAT in this slide actually unregulated in prostate cancer cells. So we can use biological pathways to recognize which cells are overusing that exact pathway with this exact molecule. And that's sort of the change of the game that we introduced for prostate cancer.
So let me emphasize what I am trying to say here. So this is how PET CT, fluciclovine PET CT will look like. And this is a patient that if you look really carefully at the CT image, again, that is conventional images, you can see in the green arrow, there is like a reverse U shape that has a center dark line inside. That is in fact a normal-appearing lymph node. It's not abnormal by location. It's not abnormal by size and it's not abnormal by morphology. Yet when we did the fluciclovine imaging using that amino acid, all of a sudden on the left side, we see a dark, and you can see on the white and black images this looks like a black dot, on the orange images it looks like an orange dot. We can actually see that the tracer showed an abnormal concentration of that tracer pointing out that there is maybe cancer in that cell.
And just to go back in time before we knew how fluciclovine is really working, we had to take that lymph node out to prove that there is really cancer inside of this lymph node. And indeed it was proven by pathology that this is metastatic disease. There was a first introduction to really understand that conventional images may not always show abnormal size and location in biological images. And in this case, fluciclovine images may actually show and point out toward localization of disease that was not known until this day. So if you look at it on a scheme compared to where we usually thought that the disease will reoccur, which is in the pelvis, now, in fact, it's outside of the pelvis and it's in the abdomen, which will require a little bit out of the box thinking of treatment way.
So before I go further, I want to emphasize that the majority of the research was done in the patient population that had suspicion of recurrent disease. So the FDA approved the indication in this investigated population and it's now approved for men who underwent treatment for prostate cancer in the past and now present with suspicious of recurrent disease based on elevated prostate-specific antigen, also known as PSA.
So I would like to cover the role of fluciclovine PET CT scan and to really understand the benefit of what this scan has to offer. And as I showed you before, one of the biggest findings of this scan that they actually can be positive when other conventional images such as CT and MRI are negative. And then another question that a lot of physicians and patients ask me, "What would you do with PSA levels? What will be the threshold where you think that this exam will be positive?" And in fact, I'm going to show you that it's not an answer that can be answered so far because there is no absolute threshold. But we do know that the higher the PSA, the higher the positive scan chance to be. And then another important fact that I would like to cover today is that fluciclovine PET CT should be considered before treatment for recurrent disease, just because it helps accurate treatment planning and that's also being proved.
So looking at that graph, it's a little bit busy, but I would like to guide you through that. In our institution, we had a peer-review publication looking at the population of patients that came to our institution and had that scan. And we found that 81% of this population had positive scans. Now, if you look at the graph, I actually divided it into different PSA levels. The left side is below 1, and then 1 to 2, 2 to 5, and above 5. And you can see that there is a linear relationship between positive findings overall in the scan in the prostate, and the extra prostate when PSA is increasing. But more importantly, I would like to take you to the left side of that graph and to show you that when PSA is less than 1, we had almost 40% of patients with extraprostatic suspicious findings. So to come and say that one should get the scan when PSA is above 1 may not be an accurate statement. So there is no real threshold, but obviously, you can see that the higher the PSA, the more chance for that scan to be positive.
So looking at a change of management, the LOCATE study that was recently published looked at the population that already had some kind of treatment plan regimen. And then they wanted to see the effect of fluciclovine PET CT and to see if that result actually changed management. And interestingly enough, you can see that out of 213 patients, 60% of this population had a change in management. And I would like you to take your attention to even more interesting detail that 30% of this population in fact had a negative scan. And why is it important? Because not only the positive scans were actually helping the clinician, making decisions about treatment and management.
So if you look forward to the next division here, out of the 60%, 78% of this population had major changes. And what does that mean? It means that if one hand, it's really hard to read it on those slides, but it does mean that if a person had, for example, hormonal therapy now changed into a completely different therapy. Or if hormonal therapy was changed to a completely different regimen compared to originally planned, other changes were tailored to the same treatment. For example, one planned to have whole pelvis radiation therapy, now will be more specific, and so on. And again, looking at that, we do see that negative scans had a lot to do with this information.
Now another sub-analysis of the same group we just recently published at looked at a population that was planning to have radiation therapy to see how fluciclovine affected those management decisions. And again, you can see in the star that the negative results had a lot to do with the decision-making of the clinicians. And of course the positive had a lot of contribution.
So how do we apply all those fluciclovine PET CT findings to action? And that's a great question. Unfortunately, when we look at everything, and because the FDA actually approved that study and it went into clinical management, less concentration on prospective studies were placed, and we could not really advise what's the best approach with these results. And why is that? It's because we don't really know yet. And I'm saying yet because it's just recently approved, not too many years. We don't really yet know the influence of fluciclovine on patient survival. And what does that mean? It means that after we end up knowing where the disease is, we need to take action accordingly. And we don't know if that action will actually lead to better survival. But that being said, until we figure that out, at least we can tell the physician if the cat is out of the bag. And that means that we do want to know if the disease is within the pelvis or outside of the pelvis.
So what are the treatment options? And again, it's really brief because this presentation is not aimed to speak about treatment. But overall, when we have early recurrence, we can choose between surveillance, which means the physician will decide to watch after your PSA and decide based on the findings what to do. Or sometimes hormonal therapy, radiation, and other discussions are being made about lymph node resection that can be before diagnostic purposes, maybe combining it into treatments, which is not very official, but all of it also will be done together with the preservation of quality of life.
So that being said, I want to show you some examples. This is a patient that was a candidate for salvage radiation therapy. And why is it so important that he had the scan? Just because when we scanned him, it was after multiple negative CTs, negative bone scans, and also negative biopsies of his prostate. And the patient had radiation therapy before and the physician assumed that the recurrence is within the pelvis and he was a candidate for additional radiation therapy. And if you look at the areas of the circle and the picture of the man on the right side, you can actually see that we did see one lymph node on the left side within the pelvis. However, the patient had what we call retroperitoneal lymph nodes, which are lymph nodes in the back of the abdomen, and also a tiny, tiny, tiny area of abnormal uptake within the bone that then proven with MRI to be true positive. So obviously this patient can not receive salvage radiation therapy because it's not going to work. He has to receive hormonal therapy. And in fact, he's still under full [inaudible] and he's doing pretty well.
So another case of another patient that had a prostatectomy in the past and his PSA went up pretty fast. And again, the assumption was that the disease came back within the pelvis probably where he had his prostatectomy. In fact, if you see again, the CT showed a little bit enlarged lymph node, but it was not known at the time of the fluciclovine images. And you can see that it's very, very bright on fluciclovine and that was highly specific based on our studies and based on our research to be prostate cancer, metastatic disease. So his physician at that point decided that she will take him into resection and she will follow up on the PSA. Number one, she wanted to prove that this is real cancer before she diagnosed that this disease went outside of the pelvis. And the second thing, she really believed that that will drop the PSA and the patient had follow-up after that.
So one of the common questions that I've been asked by physicians is that if I get fluciclovine PET CT images, do I need to do any other images to prove that I don't have or I do have bone lesions? So just to give you a little bit of an idea how it's supposed to look like, many times on CT when the images are really negative, or there is some area that the density of the bone is decreasing, what we call lytic lesions. It tends to be very intense, very bright on fluciclovine images. However, sometimes on those dense areas that you can see next to the red arrow on the CT images, when the lesions are very, very dense, sometimes the fluciclovine will not pick it up. So overall, if someone has lesions within the bones and we're seeing that on fluciclovine, even if we don't, sometimes your physician may need you to do some more images and it's really on a case-based scenario. So there is no good answer to that.
So what do you need to know? Number one, again, very important to understand that the FDA-approved indication is for recurrent disease to localize areas of disease for patients that already had prior treatment and now their PSA is increasing. The second thing, again, fluciclovine PET can be positive when conventional imaging is negative, such as CT and MRI. The third point, there is no absolute PSA threshold to obtain the scan. You do need to remember that the higher the PSA, the higher the chance that the scan will be positive, but the scan actually may be positive when PSA less than one. And the last thing, fluciclovine PET CT can affect management and it should be considered before salvage therapy for accurate treatment planning.
Thank you very much. I am Bital Savir-Baruch, nuclear medicine physician for the Department of Radiology, Nuclear Medicine Division at Loyola University Medical Center, Maywood, Illinois. And I would like to thank my group that working very hard to put these sessions together. Prostate Cancer Outreach Working Group, thank you very much, Society of Nuclear Medicine and Molecular Imaging.