PSMA PET Scan: Improving Treatment for Patients with Prostate Cancer

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic Podcast for medical professionals, exploring the latest innovative research and clinical advances in the field of oncology. Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepard, a medical oncologist here at Cleveland Clinic overseeing our Taussig phase one and sarcoma programs today. I'm happy to be joined by Dr. Rahul Tendulkar, an Associate Professor in radiation oncology here at Cleveland Clinic. He is here to talk to us about PSMA PET scans for patients with prostate cancer. Welcome Raul.

Rahul Tendulkar, MD: Thanks Dale.

Dale Shepard, MD, PhD: So maybe just start, give us a little idea. What's your role here at Cleveland Clinic?

Rahul Tendulkar, MD: Sure. So I'm a radiation oncologist here at Taussig and I've been here on the faculty since 2008 and my clinical practice has been in the treatment of genitourinary and breast cancers. Over the years, it's kind of evolved. Interestingly, as times have changed in a lot of my practice these days in the management of prostate cancer really revolves around the use of this new scan that we have, the PSMA PET scan.

Dale Shepard, MD, PhD: All right. So let's just kind of launch in, PSMA PET scan, what is that?

Rahul Tendulkar, MD: Sure. So PSMA stands for prostate specific membrane antigen. It's a protein on the surface of prostate cells. It was actually first identified about three decades ago by one of our own faculty here, Skip Heston who's in the Learner Research Institute. So there's been a long kind of history getting us to this moment. And so PSMA PET scans have evolved around the idea of attaching radio tracers that will find and hone in on these PSMA proteins on the surface of prostate cells. And that will allow us to identify low volume metastatic prostate cancers in patients with a suspected recurrence. So this has been really an important evolution in our ability to find recurrences at an earlier stage than we've ever been able to do before.

Dale Shepard, MD, PhD: So just how much more sensitive are they? So, traditionally like our old CTS and bone scans, you may have to have a PSA that's pretty high for instance, before you even think about getting one. So how has that changed when to pull the trigger on a scan with a PSMA PET scan?

Rahul Tendulkar, MD: You're exactly right. The sensitivity is so much better than bone scans or CT scans. I know when you and I were in medical school and in training together, we were taught not to bother ordering one of these tests until somebody's PSA got to at least maybe 5 or 10 or higher than that because the yield of finding something on a bone scan was going to be quite low.

Nowadays, in men who have had a prostatectomy where ideally the PSA should be close to zero, we can detect patients who may have an early recurrence with a PSA as low as 0.2 or 0.3. The yield of a PSMA scan goes up as the PSA rises. But once we get to a PSA level of approximately 0.5 or so, there's roughly a 50/50 chance of finding something pretty small. And so we can find disease as small as maybe five millimeters in size at a PSA of 0.5 or so. And so that's been really remarkable again, in context a bone scan, you might not see something until the PSA was maybe 5 or 10. So in order of magnitude, better in that context.

Dale Shepard, MD, PhD: So practically speaking, how has that changed your practice? So, we all know that guys with prostate cancer, they keep an eagle eye on that PSA. Do you have people coming in asking for scans earlier, and then are you reacting to those? Or how do you, in the real world setting, how do you deal with that?

Rahul Tendulkar, MD: So it's helped in a multitude of different ways. So right now PSMA PET scans are approved in the United States for the work up of suspected recurrence in men who have previously had treatment to their prostates, so either a prostatectomy or definitive radiation therapy. And usually after those treatments, their PSAs will go down in large part. And in those who have a subsequent rise in their PSA is when we start getting that anxiety about, all right, is this cancer coming back? Or is this maybe in somebody, who's had radiation to the prostate, maybe there's some just natural PSA being made from the gland itself. So it's a little bit hard to distinguish in that setting who might have a recurrent cancer or not. And so this has been really helpful to try to identify if a recurrence is coming back.

And I counsel patients, there are generally three places where prostate cancer tends to recur. Number one is locally in the area of the prostate if somebody still has a prostate or in the prostate bed, if it's been surgically removed. And that's one of the more common places of a recurrence, especially after a prostatectomy. Number two, a recurrence can happen in the lymph nodes in the pelvis and PSMA PET scans have been remarkably helpful at identifying early recurrences in the lymph nodes. And then number three, it can come back in the bones elsewhere in the body. And again, compared to a bone scan, a PSMA PET scan is particularly effective at finding those as well.

So we can really provide patients with a little bit more accurate assessment of where the source of their cancer might be coming from if they even have a visible one. And other times it's actually helpful to get a negative PET scan. In other words, we do the test, we don't see anything and we can reassure them that whatever is making their PSA is still microscopic at this stage. And that can affect kind of how we move forward with treatment planning.

Dale Shepard, MD, PhD: So I guess one setting where this could be considered, if you have a patient that has prostatectomy, they start having that recurrent PSA and traditionally they may get salvage radiation therapy, maybe saving people from that. How often does it happen with the conventional imaging that you would radiate someone's prostate bed, PSA still goes up and everyone gets frustrated? We might be able to avoid that. How big of a problem was that and is this a good solution?

Rahul Tendulkar, MD: Yeah, that's a great question. So historically in men with a rising PSA, the effectiveness of radiation therapy depends on the PSA level at which we're treating somebody. So for example, if somebody has a relatively low PSA, like 0.2 or in that ballpark, they might have an expected success rate with salvage radiation in the order of maybe 70, 75%, something like that. For those who have a PSA, more like 0.5 or higher that success rate drops pretty quickly, maybe 50, 60% or something like that, depending on their pathology findings.

And so that's a large percentage of people that we're treating, who then subsequently recur and may have had potentially unnecessary treatment that would subject them to side effects from that. And so this has been, I think, really helpful to try to select patients a little bit better. And I think that's been, in your world of oncology as well, I think we're seeing a lot of the recent trends and things that we're trying to achieve is really selecting the right treatment for the right patient at the right time and trying to balance aggressiveness of our treatments to the aggressiveness of how the disease is behaving and then trying to back off when we don't need to. And so I think this has been a really helpful approach.

Dale Shepard, MD, PhD: And I guess sort of continuing in that so, actually Eric Klein has been a guest on this podcast I think three times, but one of the things, particularly when we're talking about prostate cancer, he always really talks about making sure we don't over treat patients and avoiding harm. What do you foresee as the harm that might come about by doing a PSMA PET scan, finding some residual disease and say where someone had their prostate removed and then they get radiation in a setting where quite honestly not having symptoms? It may be a long period of time before it would cause them problems. What do you see as maybe the downside of early detection using this test?

Rahul Tendulkar, MD: Certainly we are still, I think, in the infancy of the PSMA PET era with regard to understanding what do we do with this information. It has really changed how we look at things and clinical trials can't happen fast enough to provide us with guidance on kind of what to do. For example, a common scenario that we see is somebody comes in with a rising PSA after prostatectomy, and let's say it shows positive lymph node in the pelvis. So do we do radiation therapy or a surgical dissect of just that lymph node? Or should we treat the remaining lymph nodes throughout the pelvis as well? Because certainly the larger volume that you treat with radiation or with surgery may result in more side effects. And so, can we take this so-called, I tell patients whack amole approach.

So if we see something, we zap it and we can do very targeted radiation therapy called stereotactic body radiation therapy, which delivers very focused radiation to small targets in an ablative manner. And so, can we use this SBRT to treat an isolated pet detected recurrence, and then spare patients from having whole pelvic radiation? And then if it comes back in another location, perhaps a couple years later, we can treat that in the same type of manner and really in an attempt to provide a long disease free interval with limited toxicity and also limited inconvenience.

One of the nicer things about this SBRT approach is treatments can be done in maybe three treatments over the course of one week, as opposed to whole pelvic radiation, which may require up to seven weeks of daily radiation. So a lot more inconvenience and a lot more side effects related to whole pelvic radiation, such as impact on bowel and bladder function.

Dale Shepard, MD, PhD: And do you think that we may ultimately sort of extend that to metastatic sites? So someone has a rising PSA, you do this sort of scan and you can find three bone lesions. So instead of, and historically they may be started on deprivation and all these other sort of systemic therapies. Can we intervene in an early age and stop sort of metastatic spread?

Rahul Tendulkar, MD: Yeah, that has been really the most exciting part about the advent of PSMA PET scans in recent years, and as well as the SBRT paradigm kind of taking off in recent years. So kind of concomitantly both of these technological improvements have really shifted how we approach this. Some recent data suggests that oligometastatic disease, so finding up to one to three positive areas on one of these pet scans can occur in about 50% of patients who do eventually have positive PET-avid lesions. And so that's actually representing a large proportion of findings is finding very early limited number of recurrences. And if they're located in places where we can safely do SBRT, it's really attractive to offer this.

There was a recent trial called the ORIOLE trial in which patients received SBRT to oligometastatic sites. So up again, up to three areas that were irradiated, and those who had SBRT to all of the PET identified sites had a distant metastasis free survival of something like 80% at two years, which is remarkable that this was without hormonal therapy or other systemic therapies at all. Just a proof of principle that giving ablative radiation to these PET identified sites can render patients free of disease for at least a couple of years in the majority of cases. So, that's really been an exciting development. And I think this has become an important part of our practice in a very short period of time.

Dale Shepard, MD, PhD: This really does totally change our perspective on what is metastatic disease. Is this an area where we're going to have to kind of rethink all of our treatments in prostate cancer in terms of when we treat and what's truly metastatic and that balance of when to treat patients and the actual effect of adding drugs in metastatic setting?

Rahul Tendulkar, MD: Yeah. I think historically the moment that we labeled something as a situation of metastatic disease, we think of it at stage four, it's incurable. There's not much we can do, we try systemic therapy until it doesn't work, and then we try something else. I think the era that we're entering, you're right, I think we have to really think about this in a new way and maybe redefine the terms that we use very, very carefully.

I look at the improvements in systemic therapy and prostate cancer as also being really remarkable. A number of new drugs that have been approved based on clinical trials that have prolonged survival for those with newly diagnosed metastatic disease. So we now have at least a handful of systemic therapies that have each independently prolonged survival compared to hormonal therapy alone.

And then when you couple that with the ability of stereotactic radiation to treat sites of gross disease, I think these drugs can be very effective at treating microscopic disease. And really, I think we're going to see a shift in terms of how we approach patients and really the goal of, I think, oncology in general, if we can't cure it up front, our goal is to turn that into a chronic disease that people can live with and have a good, healthy quality of life going forward. And so, I think that's really our aim with all of these incremental areas of progress.

Dale Shepard, MD, PhD: I mean, it's pretty significant. I mean, we're both of course quite young, but as we started practice, we really had docetaxel as a systemic therapy. Now we have two chemos and a couple hormone therapies and immunotherapies, we have more genomic based therapies, so it's pretty impressive.

Rahul Tendulkar, MD: Absolutely. Yeah. It's been really neat to see all the progress just in the last five years.

Dale Shepard, MD, PhD: When we think about, you mentioned before sort of being able to sort of redefine where you treat, and that was kind of from upfront treatment based on PET scans. And I guess a similar thing would happen for salvage radiation is sort of sparing some areas that's being treated to minimize toxicity. Anything else that's happening either from an imaging standpoint or a radiation technique standpoint that you find particularly interesting in prostate cancer?

Rahul Tendulkar, MD: Yeah. I think you mentioned genomics, that's also something that's changing a lot. So, that's a really exciting advancement. And I think we'll talk later on about predictive tools and nomograms and things like that may be useful to help guide us in making decisions. But I think integrating some of the biology that we learn from genomics, for example, with the imaging and kind of coupling those together to select very personalized treatment is really the kind of the step forward and the exciting parts that we're kind of seeing come into motion now.

Dale Shepard, MD, PhD: I guess, as we've been talking about these PSMA scans, widely available, are there difficulties with coverage in some areas or difficulty even with availability?

Rahul Tendulkar, MD: Yeah. So there are a couple of different PSMA tracers that are available in the United States. When the more recent one was FDA approved in 2021, I think that really expanded the number of centers across the country that do offer this option. We've been fortunate to have it here at Cleveland Clinic for about a year now. And again, in a very short period of time, we saw demand really through the roof. And I think it just goes to show how much clinicians and patients really kind of needing some tools like this. So yeah, as the availability has improved, I think we'll see this spreading throughout the community more and more. And I think that'll be a really great thing.

Dale Shepard, MD, PhD: I guess while we have an opportunity to get some insight, something that frequently comes up with prostate cancer and radiation proton, yes, no? Any advantages at this point?

Rahul Tendulkar, MD: Yeah. So proton therapy is something that a lot of patients ask about when they come into the clinic and you read about so many different options that are out there. We could go on about things like HIFU and cryotherapy. So along with proton therapy, there's so many things that are out there that people are interested in learning about. With proton therapy, what makes it really attractive, at least on a theoretical level, is that as the proton beam enters into tissue, it has a certain stopping point after which the proton therapy doesn't continue. And so there's no energy deposited beyond that. And we see this graphically in what we call a Bragg Peak. And so depending on how you arrange the proton beams around a target, you can really kind of minimize the overall dose to normal tissues.

The dose around the target though, is still going to get a high dose of radiation, whether you use x-ray photons or protons. And so, really the theoretical advantages of proton is to reduce some of the low dose radiation scatter throughout the body. And so, unfortunately we haven't seen yet that the hypothetical advantages of proton therapy have translated into clinical advantages just yet. And I think it's probably because the high dose deposition in the prostate and around it to the subsequent bladder and rectum, we don't quite maybe get the fall off that we would like to see that could spare those tissues. And I think also concomitantly how x-ray photon therapy has evolved and improved, we're seeing maybe similar results so far. There are really important ongoing randomized trials to compare these modalities with each other and I think until we have those data available, it's going to be hard to predict if there's going to be a winner between them, but so far I think just like any modality, protons have their pros and cons.

Dale Shepard, MD, PhD: And I guess the other modality for radiation and how it might link to our ability to target exactly where tumor might be with these new PSMA PET scans, any changes in brachytherapy?.

Rahul Tendulkar, MD: Yeah. And brachytherapy is, for those who may not be familiar with it, is implantation of radioactive materials inside and around a tumor. So in prostate cancer, there are two ways of delivering brachytherapy. One is low dose rate where we place radioactive seeds and they stay in the prostate basically forever until they fizzle out and all the radioactivity is gone. And then there's high dose rate brachytherapy where temporary catheters are placed and usually over a couple of different treatment sessions the prostate is exposed to radiation using an after loader to deposit the energy on a temporary basis. And so the patient isn't radioactive and doesn't go home with radioactivity inside of them. So just two kind of important distinctions.

But I think we're learning more and more about both of these modalities, a lot of interest in using brachytherapy for recurrent prostate cancers. And so historically, one of the perceptions of external beam radiation therapy was if a cancer recurred locally after directed radiation to the prostate, that we couldn't do more radiation a second time around and maybe surgery salvage prostatectomy was the only way to treat a recurrent prostate cancer. And there's a lot more data coming out in the last couple of years suggesting that you can use brachytherapy, either LDR or HDR brachytherapy, for locally recurrent prostate cancers.

There was a published prospective trial that was done internationally showing the efficacy and relative safety of this. So these are some areas that are, I think really exciting to see how we can integrate this to spare patients from having to have a prostatectomy if they don't want to have one. Some patients may not be medically fit for that. And so offering this as a salvage option is in one area. And then the other area where brachytherapy is of a lot of interest is using it as a boost. In other words, where we give a certain dose of radiation to the pelvic lymph nodes and the prostate, and we give a little extra dose with brachytherapy for patients with very high risk disease. And so that's another area where we're seeing some intensification of treatment that may be useful to improve our control rates.

Dale Shepard, MD, PhD: Certainly it sounds like PSMA PET scans are changing the way we think about the disease. Some exciting new things in terms of how we deliver therapies. And I appreciate you being here with us for your insights.

Rahul Tendulkar, MD: Yeah, no, thank you for having me. It's my first time on a podcast and it's been fun. So thanks for having me.

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