Brian Helfand: Thank you. I certainly appreciate the opportunity to talk here. And I think the opportunity just to talk about a lot of this data is very pertinent to most urologists, radiation oncologists, medical oncologists. Because, as you know, there are so many things that occur in prostate cancer and other urologic oncologic diseases, and many things take a long time to get set into clinical practice, but there are very few things that almost overnight we accept, and some of the things that we accept are imaging. And any advances in imaging, just because if you can see it, almost instantaneously we're believers.
And so as you know, and you certainly have lived and been a part of this whole advanced imaging, or now is referred to as molecular targeted imaging, or MTI, journey, that we've used different radiotracers to better localize prostate cancer, which helps in staging and localization of the disease, really, in all aspects after diagnosis. And certainly for higher risk disease, it helps us localize and develop treatment plans there. And certainly for recurrent and advanced cancers, certainly helps us come up with treatment plans and best treat these patients in the most personalized way that we can.
And with this, because of its increased sensitivity and specificity compared to old conventional imaging with bone scans and CT, we've really been able to redefine what metastatic disease is. And that's really kind of influenced our use of systemic therapies with or without, and certainly even targeted therapies for radiation, or even including patients that were high risk but they have localized disease and we can do more localized therapies. So it's really influenced our decision-making really throughout it.
But I think as you know that this is the U.S. and, well, it's probably the world, right? And if we do one thing, we should certainly explore and do five things in that same space. And see which one is potentially the best. And so there have been several PSMA radiotherapeutics and radiopharmaceuticals that have reached the market and are certainly commercially available. And various institutions have incorporated these largely, if you will, blindly, because we've somewhat made the assumption that they all based on their initial studies, which have various inclusion criteria and outcomes. But regardless, they all appear to be around equivalence.
And the question is, is that really a true statement? Do we incorporate them for just convenience because some are easier to mix and implement at a institution. Others are more expensive and certainly more challenging to get in at that institution. So is convenience the only thing that we should pay attention to or cost the only thing we should pay attention to?
So we set out the study to really ask that question of two F-18-labeled agents. One is, as you said, is flotufolastat, and the other one is piflufolastat. I really hate saying those names over and over again. And I think the more common are commercially available names that most people use that we're always discouraged to use, but I always ask for forgiveness in this because it's a mouthful otherwise, is Posluma and Pylarify. These are two of the more common agents that we see.
And again, based on their initial data, they both appear to have advanced the field. And when you compare them to conventional imaging, really have done well. Despite the fact that they both are PSMA targeted and they both incorporate F-18 as their radioactive element, that they are different in terms of their structure. Both have a urea backbone, but one, Posluma, is a little bit larger. And I have long forgotten a lot of my biochemistry days, but the larger the molecule certainly influences how it can be processed. And because they are initially processed and first passed through the liver, but ultimately end up with being excreted into the renal collecting system and end up in the urine, both have that ability to be processed or targeted differently.
But if you're targeted or you're processed mainly through urinary excretion, like Pylarify, and you get an accumulation in the bladder, does that ultimately impact our ability to detect any type of disease in the pelvis? Meaning that if you have a pelvic lymph node or you have a local recurrence after prostatectomy, but you have a bladder full of radioactive excreted substance, which is not cancer, that's just a normal processing of it, does that noise influence our ability to detect these differences? And that's really what this study was set out to do. So really, and again, in full disclosure, this was a BED-sponsored trial. And so with that we-
Matthew Cooperberg: Blue Earth Diagnostics, right?
Brian Helfand: Sorry, Blue Earth Diagnostics. And we prospectively enrolled 55 patients that had a prostatectomy and were starting to have a biochemical recurrence. And I say starting to because, again, as you know, conventionally, we define biochemical recurrence after prostatectomy at a level of 0.2. But data would still support that if we intervene at earlier time points, whether that's at 0.1 or up to 0.5, we may not or we may have no clinical impact. But the earlier detection, we believe, should have a positive impact on subsequent salvage treatment opportunities.
And so we still don't really recognize what is the level that these PSMA agents detect best at or, if you're going to use it at very low levels, less than 0.2, if we can detect anything or what is the frequency of detection. And additionally, again, as said, is that if you do detect something at these very low PSA levels after prostatectomy, is there going to be a difference between these two agents based on their natural processing or metabolization?
So we took men, in this study, that were on their way to or had experienced biochemical recurrence after radical surgery, and patients received two different scans. They, as part of standard of care, received the PSMA CT scan. And then several days later, they received the Posluma, the flotufolastat scan. And the main outcome was actually the intensity of the accumulation of radiotracer in the bladder. And I think that this actually shows it quite nicely here, is that when you look on the left side here at the Posluma, the flotufolastat, the intensity is significantly lower than the Pylarify the piflufolastat. And again, that is kind of obvious. And there was a SUV difference of over 10 units there. And so when you look at the mean SUV, significantly different. And you say, "Well, okay, that's great. We kind of expected that." If you use those markers or the radiotracers, that is what you expect to see.
But then the difference is, is to say, "Well, how does that clinically compare? Do we see more detection with either of those agents?" And I think number one is what is quite impressive about both agents is that even at very low levels, really under 0.2, that the detection rate is extremely high. I think that overall, about anywhere, for the Pylarify, 27 to 30% of patients had a positive scan that you could see a recurrence. And about 45% of patients even at low PSA levels had a positive scan.
So when you have that conversation with patients to say, "Is this something that we should wait or not wait on?" it's actually a much higher detection rate than I actually initially thought that would actually occur. And even at very low levels, less than 0.2, in that subset of patients, 38% and 52% had positive scans. So not a worthless exercise if you can kind of detect that.
And when you look at the differences, and this is really not a surprise, is that the Posluma scan had a higher detection rate in almost every single area and subset area that we saw. And again, that's just largely because if you have a lot of noise, if you will, that's from the excretion of the radiotracer into the bladder, that's going to potentially obscure what you can see. And this is really just showing that difference, and even there's a slight difference in pelvic lymph nodes, but obviously most of that was in the prostate bed.
So again, really, the takeaway point here is, is that if you have a scan, it is still worthwhile to help localize that disease. That's number one. Two is that if you are really concerned about the localization of where that recurrence is and you are post-prostatectomy, so very specific setting here, is that Posluma may give you additional imaging or insight into that localization because you can actually see that because of the lack of intensity or accumulation in the bladder.
So again, I think that this is just the start of looking at the differences in the available radiotracers we have. And of course, that's in the knowing that there are other radiotracers coming on the market and into play that will be also additionally besides PSMA, but probably other tag molecules as well. And so I think as we move forward here, it'll be important to really define which biomarker or combination of radiotracers that we should use at any given point to really maximize our ability to localize and develop those treatment plans that would be appropriate for those patients.
Matthew Cooperberg: That's terrific. It's great work. It's more of a difference than I think I kind of expected when I saw just the title. And I'm curious what you're doing with this clinically. So I've had this conversation with the folks at Blue Earth and at Lantheus over the years. We don't even order a specific tracer. We order PSMA PET. UCSF, we've been doing this for a number of years now. Tom Hope, who was our nuc med lead, was one of the first to get this going in North America. And we order PSMA PET. If it's internal, it tends to be a gallium scan, which we produce the gallium on our own cyclotron. It's less expensive. If they go out to community center, it kind of depends on which PET center they go to. It might be Posluma, it might be Pylarify. And as the ordering doc, I don't even necessarily have the ability to specify. So I'm curious if it's different for you or if you are actually really trying to get post-op patients specifically toward Posluma at this point. How are you using these results?
Brian Helfand: So we are somewhat spoiled. And a lot of this is because, in full disclosure, we have a lot of trials in this space that are ongoing. So we have, in our ordering system, the ability to pick and choose which radiotracer that we think... And sometimes that's influenced by the ordering physician. I have a lot more opinions probably, but a lot of times it's also if it's dealer's choice, they will almost by default revert to the gallium just because it's easier to order.
And we haven't had those comparative studies as of yet. Certainly anecdotally, when we look at SUVs, they seem to be, at least at our institution, higher per finding that we have with the gallium than some of the others.
And so as we're starting to recognize that there may be some prognostic value to SUVs as well, it'll be interesting to see how that influences, that and the outcomes.
I do think that with this prospective data in that recurrent space, I'm now leaning more towards the Posluma because it is easier potentially to see and localize that. Ultimately, as you are bringing up, is how does that impact the treatment plan? And for most of those patients, just based, again, on timing and other clinical factors, it's going to almost statistically set us up for a treatment plan, meaning that if it's negative or positive and we're making the assumption that most of it's within that prostate bed area, that we're probably going to radiate that and plus or minus hormone therapy. May be dependent on other factors, what their Gleason score was before, potentially what their Decipher score was, things like that that may ultimately impact the use of hormone therapy.
And it's hard to argue, and I think people are now prospectively asking that question, is if people have negative scans, should we wait until we see something positive before we start doing salvage therapy? And I think that's a very interesting question to ask. On the other hand is we do know that from the data now for many years, if you have a negative scan, it's not a bad thing.
Matthew Cooperberg: Right, right.
Brian Helfand: And those patients respond really well, and they do better. And so is that because we intervened earlier? Is it because we overtreated them?
Matthew Cooperberg: Exactly.
Brian Helfand: So I think time will tell us, but that's where... I think these questions are very pertinent. I don't think we're making small strides here. I don't think a lot of this is earth-shattering. But on the other hand is I think these are very important questions that we need answers to that we ultimately to better treat these patients in the right way.
Matthew Cooperberg: Absolutely. And as PSMA PET probably continues to gain traction in local staging, this question about the bladder and shadows from the bladder and SUV in the bladder are going to become more relevant. So thank you for leading this work. I think it's really interesting, and it's a terrific space. As you say, there's new tracers coming out. We'll be able to interrogate more about the biology with imaging as we go forward, how we combine this with MRI. All the things in the pipeline are all really, really exciting. So great space to watch.
Brian Helfand: Definitely excited about it.
Matthew Cooperberg: Well, thanks for joining us.
Brian Helfand: Definitely. As well.