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Published on December 14, 2020
What Do PSA and Next Generation Imaging Tests Mean for Prostate Cancer Patients?
In this segment of our prostate cancer Answers Now series, a panel of prostate cancer experts and advocates discuss the latest developments in testing and imaging for prostate cancer. What tests should patients receive, and when? What can PSMA PET and Next Generation Imaging mean for individuals at different points in their prostate cancer journey? Find out in the video above.
Experts include Scott Tagawa, MD, Professor of Medicine and Urology at New York-Presbyterian-Weill Cornell Medical Center and David VanderWeele, MD, PhD, Assistant Professor of Medicine in the Division of Hematology and Oncology at Robert H. Lurie Comprehensive Cancer Center of Northwestern University. The discussion is guided by Patient Power co-founder Andrew Schorr, as well as AnCan Prostate Cancer Moderators Len Sierra and Peter Kafka.
This program is sponsored by Bayer. This organization has no editorial control. It is produced by Patient Power. Patient Power is solely responsible for program content.
Transcript | PSA Test and Imaging for Prostate Cancer Patients
Andrew Schorr: Greetings. I'm Andrew Schorr, co-founder of Patient Power. Thank you so much for joining us for the second in our series of Patient Power programs produced in association with AnCan, a wonderful advocacy group that you may know, or if you don't, you're going to hear more about it and I hope you'll take advantage of their support groups and services.
I want to just mention, we have from AnCan, we've got Len Sierra, and Len is joining us from Danbury, Connecticut. He's a board member of AnCan, and Len is dealing with high risk, recurrent, advanced prostate cancer. So he knows the territory. Len, thank you for being with us. And also, the president of the board of AnCan, and that is Peter Kafka, Peter joins us from the jungle area of Maui. Haiku, Maui. So quite a ways from where I am, today I'm in Durango, Colorado. And Peter, thank you for joining us.
So, I want to introduce Dr. Scott Tagawa, who is Professor of Medicine and Neurology at Weill Cornell Medicine and a physician at New York Presbyterian, who joins us from New York City. Dr. Tagawa, thank you for joining us.
Dr. Tagawa: Thanks for your invitation, I'm happy to be here.
Andrew Schorr: Okay. And now let's skip over to Chicago, and that's where we have Dr. David VanderWeele, who's an Assistant Professor of Medicine at Northwestern University's Feinberg School of Medicine. He's a Medical Oncologist at the Lurie Cancer Center at Northwestern Memorial Hospital. Dr. VanderWeele, thank you so much for being with us.
Dr. VanderWeele: Great, thanks for having me. Happy to be here.
Andrew Schorr: So on to you, Len, take it away.
Len Sierra: As Andrew suggested, we'll start off with some basics. Dr. Tagawa, let me address this question to you first, and then to Dr. VanderWeele. Most of our audience is probably familiar with PSA, but perhaps not so familiar with PSMA. Can you please explain the difference between these two?
What is the Difference Between PSA and PSMA Tests?
Dr. Tagawa: The difference is simply one letter. And I'm not being facetious when I say that, I think it's a good explanation. If this is a prostate cell, which makes PSA, or a prostate cancer cell, PSA is made inside and also goes out. The "M" in PSMA in "Membrane," so it's stuck to the surface, and the only way it's going to travel is if the cell travels. So that's the major difference, we call PSMA a cell surface antigen, think of it as a lock that a key might be able to find on the surface of that type of the cell.
Len Sierra: All right. Dr. VanderWeele, anything you want to add to that?
Dr. VanderWeele: Yeah. That has important implications for how those things are used. Because PSA often is secreted out of the cell, we can do a simple blood test to measure PSA level, and that may give us some indication of the number of cancer cells or the activity of the cancer cells that are in the body, although it doesn't say anything about where it is. Because, as Dr. Tagawa said, PSMA is locked onto the surface of the cell, if we can detect where PSMA is, then that can actually give us a sense of location and where the cancer cells are.
Len Sierra: That's a good lead into my next question, so let's stay with you, Dr. VanderWeele, for the moment. Is PSA alone a good marker for recurrent or advanced cancer?
Can PSA be a Marker for Recurrent or Advanced Prostate Cancer?
Dr. VanderWeele: PSA can be a very helpful marker for us. Most patients who have had their prostate removed with a prostatectomy, we would expect that if they are cured, that their PSA would be undetectable at that point. If you have prostate cancer treated with radiation, that's not necessarily the case, but we do expect the PSA to be low.
And because only prostate cells or prostate cancer cells make PSA, if there's a rise in the PSA, or an increase in PSA, that usually means that there's an increasing number of cells or increased activity from those cancer cells. And that's usually pretty sensitive, too. So much of the time, if PSA starts to go up, that can give an indication that the cancer is on the move or that the cancer is active, and typically that happens before we would see any changes on imaging, so for instance on a bone scan or on a CT scan. That's not always the case, but it's typically a pretty good marker for us.
Len Sierra: So now, Peter and my prostate cancer support activities, we do notice that there are some patients who seem to produce a lot more PSA than others, even when their Gleason scores are the same, right off the bat. Sometimes we wonder if a low PSA with an advanced Gleason score is a bad sign.
Dr. Tagawa: Yeah, I wouldn't necessarily call an individual PSA high or low necessarily good or bad. I would say that within an individual who has already been diagnosed with prostate cancer, PSA usually tracks with disease, but it would not be correct to compare one man's PSA of 10 to another man's PSA of 10, one could be much worse or better than another one.
It does tell us about some of the activity, and actually some of the biology of the prostate cancer, what's going on inside of the cell, so that helps us a little bit on the scientific level and treatment level, but there are men, let's say a man is not known to have prostate cancer can have a high PSA above 10 and not have prostate cancer, and some with a PSA that is less than one have prostate cancer.
And similarly, patients diagnosed with prostate cancer, it could be not a big deal when it goes up, and there are cases when cancer does get worse despite a low PSA. So it's a good test, but it's not perfect.
Len Sierra: Dr. VanderWeele, can you define for us what PSMA imaging is, when is it appropriately used, and perhaps explain a little bit about its advantages or maybe disadvantages to existing scanning tools that we have?
What Is PSMA Imaging, and What Does it Mean for Prostate Cancer Patients?
Dr. VanderWeele: PSMA imaging, typically what we're talking about is PSMA PET scan, and in order to obtain that scan, usually a patient receives an infusion or injection with something, some kind of agent that binds to PSMA and that also lights up on the scan. And so after you receive that infusion, that agent that you receive will go into the body, throughout the whole body, and bind to wherever the PSMA is, and then you can take a scan, take imaging and see where it's lighting up.
Now, typically PSMA is much more highly expressed on prostate cancer cells than on other cells. PSMA can also be expressed by some other cells, like salivary glands and kidney, but usually much higher on prostate cancer cells. And so it can be a good way of telling us where the prostate cancer is located.
The advantage of a PSMA scan is that it appears to be much more sensitive than conventional imaging, than a CT scan or a bone scan. So, the place where it's being looked at the most right now is for someone who had the prostate cancer treated, but now the PSA is rising and there's some suspicion that the prostate cancer has come back and is starting to grow again, and if someone undergoes regular imaging or conventional imaging with a CT scan or a bone scan, there might not be enough cancer cells in one place that it would show up on those scans, but you might then come in and do a PSMA PET scan and that might actually show where the cancer is.
And so, where it's being used mostly is what we call biochemically recurrent prostate cancer. So the PSA is rising but the conventional scans, regular scans aren't telling us where the cancer is, but these newer scans, PSMA PET scans can be more sensitive to tell us that information.
Peter Kafka: Let's move on to logistics. With the logistics of PSMA scans and the sophistication of the technology, are there going to be a limited number of centers that can possibly perform these scans?
How Accessible Are PSMA and PET Scans?
Dr. Tagawa: I think the answer is going to be "Yes, initially," as the answer to your yes or no question. But let me take a step back. PSMA is, as we've discussed in the beginning, a target, and there are different ways of getting to the target, many different types of compounds, and they will get attached to different types of radioactive particles that do different things such as light up, and that's what we're talking about.
But more directly answering your question, I think that the most likely initial approval for PSMA PET is going to be specifically something that's called Gallium 68 PSMA 11. That's what you had in San Francisco. And many of you have heard of C-11 Choline, that is an academic center submitting something to the FDA and trying to get approval, and I think that's going to happen pretty soon. That's approval for those centers, that was a joint application between UCLA and UCSF, and those are the only two places that are going to be available initially, and then other centers can then apply for that.
But that is only going to be available when the centers have the ability to do it themselves. What should be coming on the heels of that is the kit to be able to make that, so other places that have less technology would be able to do that, and then pharmaceutical companies coming in with their own PET agents to lead to approval. And then I think it's going to be much more widely available. But I know from talking to colleagues across the country, one of the most common types of PET ever used for cancer is something we call an F-18 FDG, it's not available everywhere, even though it's been out for a very long time. There are people that have to drive three hours because there has to be a center that has a PET machine. So I don't think it's going to be widely available next door, but I do think over the next couple of years, it's going to be much more available than having to fly across the country.
Andrew Schorr: So, we’re people around the country, we've gotten people in Minnesota and New Jersey say "Okay, this technology is not broadly available yet," and as you said, Dr. T, we don't know exactly when the approval will come or these kits to do it in other places. So given that, for both of you as practitioners, for a man living with more advanced prostate cancer today, where you as a practitioner and the man as a patient want the best possible picture of what's going on to make decisions on what to do, how do you feel about the tools you have now?
Dr. VanderWeele: Yeah, that's a very good question, and actually we do not have PSMA PET scans available on a research basis or otherwise, not currently, so I have actually had patients travel to other states to get that done, to Indiana or to Michigan to get a PSMA scan. There are also other PET scans trying to do the same thing, so Fluciclovine or Axumin PET scan that is available and that we can offer here at Northwestern. That is also a scan that's more sensitive than conventional scans, so more sensitive than a CT scan and a bone scan and can show us where the prostate cancer is even when those scans are negative and look clean. I'd say both of them are significantly more sensitive than conventional imaging.
Andrew Schorr: Dr. T, how about you? Because again, a man comes to you in New York, maybe there's not this advanced, still experimental in some cases, type of PET scanning, should he feel he's not getting state of the art care?
Dr. Tagawa: Well, if we're talking about someone that has prostate cancer that's been treated and the PSA comes back or goes up, [inaudible] recurrence, it's highly dependent on the sensitivity, which is highly dependent on what the PSA level is. So if the PSA is above two or above one, not so high in the scheme of things, but relatively high if it went from zero. Currently, the second generation of imaging agents such as Fluciclovine or Choline is pretty good. Much better than old fashioned CT, MRI, bone scan. Especially, however, for PSAs less than one is where the higher sensitivity will make a major difference.
So, let's say I have a man with a PSA of .5, I think it's entirely reasonable to do what's available, Fluciclovine for instance, because if it shows something, it shows something, and then we use that information. If it doesn't show something, then that's where it might be worth it, on a case by case basis, to say "Okay, it is worth it to travel," and sometimes that travel is one state over, sometimes that travel is multiple states over, sometimes it is to a different country. So, it depends on a case-by-case basis, largely having to do with what are the treatment implications, because sometimes it changes things by a little bit, and sometimes it would change things by a lot.
Len Sierra: And Dr. T, suppose you have a patient, and once again, we'll fast forward to a time when PSMA PET scans are approved, if you have a patient who has a PSA that isn't very low, maybe it's five or 10 or 20, would you still prefer to use the PSMA PET scan or would you feel that some of the older scans like Axumin, not that old, but traditional bone scan, would that be just as effective in locating lesions?
What Are the Similarities and Differences Between Traditional and Advanced Scans?
Dr. Tagawa: You threw in that last phrase, "locating lesions." The more sensitive imaging agents are always going to locate more lesions, but that is not necessarily the goal. My goal for a patient sitting in front of me and/or his family is to increase length of life and maintain or improve quality of life, and sometimes a PSA going up or a scan showing something abnormal impacts quality of life at least for that moment in terms of anxiety, but that's not really what I'm talking about.
The more important for me is that situation, what are the implications in terms of how long might someone live? And especially the implications of what treatment might I recommend next. The old fashioned scans such as a bone scan has the advantage of having a long history of when it's positive, we know exactly what it means, what the implications are and how to follow that over time. And it's cheaper. But head to head it's clearly going to show less cancer. It doesn't mean doing one scan today and another scan tomorrow really changes the amount of cancer that's there. So it really depends on what I'm thinking for the next step.
So in the situation, let's go back to the same situation, low testosterone from treatment, PSA going up, some of the time I want to find something either because I want a man to qualify for a treatment that requires us to see something, or I want to find something maybe hoping it's one or two places to take care of, maybe not changing the long term outcome in terms of how many years are left, but because I want to avoid a different drug or push back a different drug. So it depends on the individual situation, and I think that's much more important for us to think about the next step versus just doing something fancy because it's available.
Andrew Schorr: This is for Dr. VanderWeele. What prostate anatomical artifacts can mimic cancerous lesions when interpreting an MRI?
Dr. VanderWeele: If I understand the question correctly, we're switching to prostate MRIs and what may cloud the picture.
Andrew Schorr: Right.
Dr. VanderWeele: And certainly, if there is inflammation, like prostatitis, that can make it much more difficult to interpret the prostate MRI and to know if there is cancer in there that's clouded by or hidden by the inflammation that you see, or if the abnormal findings are all related to inflammation and not related to cancer at all. I think that's probably a major one. I'm not a radiologist and so I'm sure there's a much more exhaustive list, but I think that's a common scenario that provides a conundrum for radiologists.
Andrew Schorr: Here's a question we got in, and Dr. T, I'll ask you this, it says is a PSMA PET scan useful for someone who is on active surveillance?
Is a PSMA PET Scan Useful for Patients on Active Surveillance?
Dr. Tagawa: It's a good question. I would say if I had to answer yes or no, I would say no, because we don't have enough information, but we are using that patient population, enrolling that patient population in research, so there is an association, meaning a link between the Gleason score and PSMA, so generally someone on active surveillance has a low Gleason score and not much cancer, based on MRI, ultrasound, biopsy, et cetera. It is possible that a PSMA PET scan might show a hidden Gleason grade group three, four or five and highlight something that may be missing on an MRI. That's under research right now, so I would say that is not going to be the initial use for PSMA PET once it gets approved, But it could supplement some of that information in the future.
Peter Kafka: So these scans were probably going to be approved for recurrent disease as opposed to the broader use, is that what I'm hearing?
Dr. Tagawa: Well, we don't know. Initially, it looks like it may be ... actually, it's a pretty broad statement, so patients with metastatic lesions might be able to get one, but it's for either men walking in the door with high risk, I mean, it's actually not so different than Fluciclovine right now, walking the door with high risk, meaning high PSA, high Gleason score, thinking about surgery, radiation, could there be something else that we're not seeing on that? So that will be one useful situation, and probably the biggest is like we've been talking about, some sort of treatment and then PSA goes up, where is the PSA coming from?
Peter Kafka: I've noticed many men are quite nervous about radiation exposure since PSMA scans are an injection of a radioactive agent. Men who have to have multiple scans or frequent scans or whatever, do they have a right to be nervous about radiation exposure? Is there a limit to these things?
What Are Your Thoughts on PSMA Scans and Radiation Exposure?
Dr. Tagawa: Certainly, every man has a right to be nervous about whatever he wants to be. In the scheme of things ... there are two parts to radiation, let's say with a scan. One is what is injected, so sometimes that's a radioactive material, in the case of a PET scan or a SPECT scan like a bone scan, and some of the time it's what we call contrasting material and it's not radioactive. But anyway, the injection part is sometimes radioactive, it's sometimes not. And then the scan part is sometimes radioactive, and sometimes it's not. For most PSMA PETs and for most other PETs, it's a dual type of radiation because the injection has radiation and the scanner has radiation. The injected radiation, generally speaking, is pretty small compared to ... nowhere near what we'd expect with radiation treatments. There is often a CT scan combined with the PET scan, so that does add extra, although it can be combined with an MRI which would not have radiation that's there.
That being said, we generally do scans, particularly these specialized scans, at particular points for a reason, and for me or my patients or family members et cetera, I have zero qualms about doing a PET scan even more than once at certain times, because what I want to know is worth that risk. Just don't do it every day.
Andrew Schorr: We have men, many with more advanced prostate cancer, and they want to feel whether it's with these technologies as they come on board, do you feel like you're getting an ever-clearer picture to help them get the treatment they need and deserve?
Are Advanced Tests and Scans Helpful in Determining an Individual’s Course of Care?
Dr. VanderWeele: Yeah. I do think that these scans are very helpful. We've been fortunate in this disease that the PSA is, as we talked about the very beginning, is a pretty good marker of if there's cancer there, especially once someone's had cancer treated, so following that along. But it doesn't tell us anything about location typically. So these scans can be very helpful in helping to tell us, even when the PSA is very low, even when there's a small amount of cancer in the body, where exactly is that cancer? And we're learning more and more about what to do in those scenarios, and can we still have a significant impact on overall survival by targeting that cancer in that specific location? Which I think will be the real promise of these scans. Not only the information they give us, but how can we really best use that information to impact the length and quality of life?
Andrew Schorr: Right, length and quality of life, that's what it's about. Dr. Tagawa, before we let you go, a final comment from you as we've had this discussion today?
What Final Thoughts Do You Have for Prostate Cancer Patients Watching?
Dr. Tagawa: Yeah, what's nice in the current era, I would say, of treating men with prostate cancer is we have many more options than we did just a short number of years ago, and those have to do with a combination of both diagnostics such as scans or genetic testing, biopsy et cetera, as well as treatment. So it's very nice to see that and it's nice to see them coming together.
To address several of the questions I saw in the Q&A that had to do with different types and availability of these scans, what I would suggest both for treatment as well as imaging is to be your own advocate and advocate for your loved ones and just ask the question. Some of the times, I would say it's not worth it to even travel across the street to get a fancy scan because it's not going to make a difference, and other times it would make a major difference to travel for that.
So, ask, and specifically for PSMA PET, there are a number of different agents out there that are confusing even for me, they're very, very similar. So if one's available one state over and one's available 10 states over or in a different country, it probably doesn't matter so much. So don't look only for Gallium or only for Fluorine-18 or these different acronyms that we look for. PSMA imaging, I think at least for the beginning, is interchangeable. So any of those will be okay.
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