Jennifer Linehan: Hi there. I'm Jen Linehan. I'm an associate professor of urologic oncology at the St. John's Cancer Institute in Santa Monica, California. And I am going to talk today a little bit about the Oncuria-Detect test. And this was a test that was really sort of formulated for bladder cancer and came out of studies in muscle-invasive bladder cancer. And then we tested a group of patients with upper tract tumors to see sort of the validity of the test. And if this is another molecular marker that we could be using in our practice to help identify and probably more importantly follow surveillance in a lot of these patients. In my practice, I do see a significant amount of Lynch patients and I'm always getting asked the question, how are you going to watch me? Do I get ultrasounds? Do I get CAT scans? Is urine cytology even helpful? So when we found this test and tested it in upper tract patients, I think it's really going to prove to be useful in our practice and hopefully keep our patients from having some unnecessary procedures. So what is the test really? The test is a noninvasive urine test. It is done on voided urinary specimens, and these are urine, which for the most part we can get from patients. And it's a multiplex urine test and it's based on protein concentrations. It has a lockout algorithm of about 0.5 as far as how much protein that they're looking for in the urine.
And the output is basically reported as a binary result. There's either cancer or no cancer, and it's really derived to help us use these molecular markers, use these proteins to aid in clinical decision making. Again, this is voided urine cytology. And we know that in our practice now, oftentimes getting a voided urine cytology on a patient is not really going to be very helpful with upper tract urothelial carcinoma. And while these can have a high specificity, they have a very limited sensitivity, especially for upper tract. If you're doing selective cytology, it's the same thing, even though we're up in the renal pelvis and we're getting the urine directly from the kidney, this is invasive and also still imperfect. And if you actually look at the sensitivity and specificity for voided urine cytology, especially for upper tract, it's less than sometimes 50% specificity sensitivity for these patients. So it's not really a technique that we can use for our patients. And again, even selective cytology only still has a limited maybe at best, 70% sensitivity. And again, that can be an invasive test and you may not be able to do that in every patient. We also implore imaging techniques and try to use all these in combination, but if the lesions are small or perhaps you don't have the best delayed imaging, you're going to miss some smaller tumors even if they are high grade. So having a urine molecular test assay that can be done in most offices, and even if it's a send-out test and comes back, it really can help us diagnose what patients need to be screened at a higher level, patients that we need to be taking to the operating room to take a look up in the kidney. So this test, we tested this. It was about seven different centers and we had 120 patients. We had 60 patients that had biopsy-proven upper tract urothelial carcinoma, and those patients were all comers.
They were low-grade, high-grade invasive, most patients were in their seventies. Most of the tumors were in the renal pelvis, which is very common for upper tract. And then this was matched to 60 control patients, again, voided urine specimens of patients who had no history of any kind of bladder cancer or upper tract urothelial carcinoma. And if you really look at the data inside this paper, if you look at the Oncuria test versus just a urine cytology just in the test alone, the sensitivity was about 0.92%. But the important part of the test was that the negative predictive value of the test was about 0.88%. And I think that's the real value add for urologists in their office. And what impressed me most in this population was that that was even apparent in low-grade upper tract patients that the ONCURIA test provided still 0.94% sensitivity in the test and a high negative predictive value because I think even in bladder cancer, if you have low-grade tumors in the bladder using a voided urine cytology still only best gets you 60% sensitivity at times. So those were the things that I was most impressed about in the test that it wasn't just in these high-grade patients. So these were some of just the patient overall. They looked at the Oncuria test versus voided cytology versus selective cytology. And in my practice, I always thought that the selective cytology really could help me rule out what was there or not there if, especially in patients that had CIS or very small tumors, especially in instances where I thought that the tumor might be low grade but wanted to rule out that there might be a high-grade lesion leaning in the background. But even in selective cytology, if you looked at it compared with the Oncuria test, the sensitivity is only 0.82%. And compared to the sensitivity in the Oncuria, which was 0.9%, and again, a negative predictive value was close to the nineties for this test.
So I think whether you have a low grade, high grade, non-invasive or invasive patient, it still is going to give you some molecular background to what you're looking at. Now, I think, again, there's only 60 patients in this study, so we have to continue to gather more samples and study more patients. But again, I think compared to what we have in our repertoire today that the test really could help us to screen some patients and give some patients some comfort or decide who's going to be taken to the operating room. So just to go over the diagnostic performance of this test, again, the benefits are high sensitivity, high negative predictive value, detects high grade and invasive tumors, as well as low grade tumors. And we observe the same performance of the test over all the different patient populations in again, a voided urine specimen. So the clinical value is that this is something that we can combine with imaging. This is something that you can use in selective urine samples. I was thinking it was hard to get 50 to a hundred CCs of selective urine samples, but I think if we knew that we were going to be doing this in a setting where it was really going to make a difference in a clinical diagnosis, that it would be worth trying to get that much urine if we needed to by just doing some barbotages up in the kidney. It's combined with obviously doing your ureteroscopy at the same time and provides some more molecular information. And really, again, the test is just an immunoassay. So in general, these tests could be done in different centers, but this is more a send-out test that we would do in the office and send out. So I would compare it to a lot how we use PSA in prostate cancer. You might be getting a PSA test, but you might also be doing a SelectMDx or something like that to help you guide the patient in basically their diagnosis and how you want to treat them.
But for me, the clinical utility is going to be in surveillance, not just screening, but finding the patients that I know had low-grade tumors and then using this test in combination with imaging to figure out who I need to take back to the operating room. So again, it's a very small study at this point, and I think we need to gather more samples. And this is why with these patients, they're relatively rare. These trials have to be through multi-centers because it's just the only way to gather enough urine samples. And in our institution, we usually get the urine obviously and post-op following them and as well as correlating that with the biopsy information. And one of the questions that I had asked in the beginning when I was doing the trial is how did they decide on these 10 biomarkers and the biomarkers that they're using are a common set of biomarkers that are known to be associated with invasive cancers. And originally I think they had 19 biomarkers that they looked at. And again, mostly the studies, the original studies were done in muscle-invasive or high-grade bladder cancer. And when they came to these 10 that were found in cancer patients and then testing those in different group populations. And the one thing for me about the study as well is that I had thought... The question of the upper tract was a different biological cancer, but when I look at the molecular markers from this test and finding them as useful as they are in upper tract, maybe it is more similar to lower grade and bladder cancers than we think. So I think there were a lot of things that I got out of this study in this paper as far as what our capabilities are going to be over the next few years in following these patients.
Sam Chang: Jen, that was a great overview of the manuscript looking at the ONCURIA test in those patients with upper tract urothelial carcinoma. Tell me kind of now how you use this test in that upper tract population and in either diagnosis or screening or evaluation of therapeutic efficacy. How do you use the test?
Jennifer Linehan: I think this test is very exciting for upper tract because really before this test, we did not have anything that sort of matched its ability, especially the negative predictive value that it has. And so for me, I see myself using it not only in selective cytology from the kidney in patients that I'm under surveillance, but also to help screen patients in the clinic, patients who are coming in with new masses or new filling defects that they're seen on imaging and using that in combination with the imaging at the same time. And again, are these patients that I need to go do any ureteroscopy? And as we know, a lot of these patients are older in their late seventies or in their eighties. It's not great to be taking the patients to the operating room every three months to do ureteroscopy. So this is something that I can use in combination with imaging to help give myself comfort and the patient a little bit of comfort that there's nothing there. I think that's going to be the best utility of this test.
Sam Chang: You can see the combination of a diagnostic test in terms of imaging with a urinary marker. Boy, if you could avoid the, right now, our gold standard is the ureteroscopy is a direct visualization, but boy, if you can avoid that, put it off, obviously at this point, can't replace it, but just as you said, if you can put things off. And then you also have a secondary situation where the radiologist will read a possible small area that hadn't been there. You're not so sure and someone perhaps that's lower risk, perhaps you get this test, oh, this looks good. Let's not take you to the operating room. We can do a follow-up imaging, et cetera. If it comes back positive, you've got the sensitivity. You've got things where, okay, that's going to drive you to do something. But just as you say, the negative predictive value is helpful, especially with the upper tract disease. Tell me where you guys are thinking or what you're thinking next, the investigators will go in terms of helping to bring this more broadly into practice. You were saying these are small cohorts, they're case-control matched in terms of upper tracts and the case controls. Tell me where you want to go next from a multi-center investigation project.
Jennifer Linehan: I think really at this point, we took all comers. So as any patient with upper tract, low grade, high grade invasive, everything. So I think we need to really tease out each of those groups and evaluate the test in 60 low-grade patients, in 60 high-grade patients, invasive versus noninvasive, and see how the test functions in those groups. Because if really you can preserve the sensitivity and specificity that we're finding in a voided urine specimen, even in a patient with low-grade upper tract, that you can potentially use that even as a screening tool.
Sam Chang: Oh, yeah. Think about it. I mean, as you pointed out, the test that we've used historically for so long, the urine cytology is really, it's an ineffective test. It is very specific, but ineffective, especially for the lower-grade disease. And especially it's been unclear regarding upper tracts. So you can really see the utilization with the test. This is the last question. Tell me, do you use this test in your bladder patients, so separate from upper tract in your bladder cancer? And if you do, again, how do you integrate it into your practice?
Jennifer Linehan: So the validity I think for this test is patients who are sensitive or more resistant, I should say, to BCG therapy. So one of the things they did with this, the 10 protein tests, is they looked at patients who were sensitive to BCG. And I think that's the biggest role that I will find in my practice because we have a BCG shortage. So if I can do this test that says, well, you're really not going to have that great of a response, we should think about something else that I think will be the biggest benefit.
Sam Chang: Yeah, that's very helpful in terms of you hate to in some way ration treatment and you want to be as fair as possible, but if you have some information upfront that can help guide you to, this is probably not as likely to be as effective. And if we can go this, and especially in a tight supply, you can see how that's going to be something that you can integrate into your practice. Well, Jen, thank you so much. Really admire all the innovations that you've done in terms of, like I said before, the robotics and minimally invasive, but your interest in upper tract and urothelial carcinoma has really made real inroads with the research that you and your collaborators have done. So we look forward to having you again and to speaking to you again as we get more and more data and information.
Jennifer Linehan: Thank you.