Neal Shore: Hi everyone. I'm Neal Shore. I'm the Medical Director of the Carolina Urologic Research Center. Welcome to our program today, "Alternative Strategies to Deliver Urology Care and Bladder Cancer Investigation during COVID 19 and assuredly Beyond". How are we responding now and our preparedness for the future? I'm really happy to be joined by Sima Porten who is an Assistant Professor of Urologic Oncology at UCSF as well as Dr. Tom Nifong who's the Medical Director of Pacific Edge Diagnostics in the United States. So welcome, everybody. We're going to first get Tom's review of the biomarkers, specifically urine biomarkers known as the Cxbladder products. He's going to review very quickly but concisely how you can use these products and then Sima and I are going to discuss I think a really vanguard approach to remote testing and how to use telemedicine, remote testing and how to really augment patient safety and therapeutics and decision making. So Tom, thanks.

Thomas Nifong: Thanks, Neal. Certainly happy to give a very brief overview. Cxbladder is a suite of three urine-based multianalyte algorithmic assays, or MAAAs, for detecting bladder cancer. The genomic tests measure the messenger RNA gene expression levels of four cancer genes and one inflammatory gene and incorporate these biomarker levels along with certain patient risk factors into algorithms to identify patients at lower or higher risk of having bladder cancer. Cxbladder is validated in two bladder cancer pathways, hematuria evaluations for primary detection and surveillance for recurrence in nonmuscle-invasive bladder cancer. In hematuria, there are two separate algorithms. Cxbladder Triage and Cxbladder Detect. Cxbladder Triage is a pure rule-out test with a very high sensitivity of 95%, and an NPV of almost 99%. It is designed to stratify low-risk patients and is used primarily for lower risk asymptomatic microhematuria patients before doing a full urologic evaluation who you may be willing to defer working up at this time.

Cxbladder Detect provides the balance of sensitivity and specificity to provide value in higher risk hematuria patients such as in patients who have equivocal cystoscopy or atypical cytology, where the high specificity of 94% and positive predictive value of 68% can help you decide if additional evaluation is warranted. Cxbladder Monitor is a pure rule-out test with a high sensitivity of 93%, and an NPV of 97% to be used to stratify lower-risk patients with nonmuscle-invasive bladder cancer who are undergoing surveillance for recurrence primarily where you may be willing to defer a full urologic evaluation at this time based on the Cxbladder result.

Neal Shore: So Tom, that was a great overview and of course this has been years and numerous papers that have demonstrated the clinical utility for using these three different Cxbladder tests. I want to highlight in our next slide a paper that was recently published in European Urology and Sima was part of this paper as was I was led by Badri Konety at the University of Minnesota, senior author, Yair Lotan. And I think this was a really provocative paper where we looked at over 2000 patients to get a better understanding of the role of Cxbladder regarding atypical cytology. And I'm just going to present here, not a full review of that paper, but the study conclusions. We've previously done on UroToday a really nice interview, an excellent presentation by Badri Konety where he reviewed the paper in depth.

But essentially the study conclusions were that Cxbladder significantly outperformed urine cytology for identifying patients with urothelial carcinoma. It correctly adjudicated all atypical cytology and atypical cytology with equivocal cystoscopy. There was with Cxbladder and cystoscopy concordance of all positive cases that were previously categorized as atypical. And then the fourth bullet here is, as I said, the significant utility that's gained and at the same time avoiding 35% of patients undergoing cystoscopy. That becomes relevant given the value-based propositions of healthcare as well as the time and potential minor, albeit real morbidity for patients undergoing cystoscopy.

So the conclusions of the paper I think were pretty provocative in that using the Cxbladder biomarker as either a reflex to cytology or as a replacement for cytology and helping our colleagues and medical oncologists, urologists, in some countries primary care physicians, help with the diagnostic dilemma associated with atypical cytology in equivalent cystoscopy results. So let me transition over to my colleague and friend, Sima Porten. We're really all grappling with how to best adapt to new strategies to take good care of our patients who either have bladder cancer, have hematuria evaluations. How are you doing it at UCSF?

Sima Porten: Yeah, sure. So, in San Francisco, our mandate for shelter in place came fairly early. We've been lucky in terms of the hit that we're taking from COVID happens to be a lot less than some of the other reports described in the country, but there are a lot of downstream effects from that early shelter in place order, mainly that it affects the ability and safety of our patients to get to us. So, schools were closed. People now have to figure out how to take care of their children at home, work from home. They're not able to come drive the two to three hours, sometimes six hours depending on where you live in California and are coming to see us for their cystoscopy, for their healthcare. If they relied on family members to drive them, many are sheltering in place separate from their family members because they're elderly or immunocompromised for other reasons. So that created a pretty rough situation for even if we wanted to do cystoscopies in everybody who was on surveillance and we thought that that was important or when looking at the risk-benefit ratio feasible to do, it would be really difficult for people to actually accomplish that for multiple reasons.

The other side of it is what's happening within our own healthcare system, minimizing clinic staff, minimizing staff that cleans assistant scopes, minimizing staff at check-in. All of this leads to a situation where a home-based urine test to be able to safely say that someone can skip that cystoscopy in their surveillance schedule became very useful from both our perspective as physicians and also patient's perspective too, in wanting to stick with that schedule that they had been told is so important. And yet now we're saying that well, maybe we can't do this. When we look at this risk-benefit ratio, this provided a really great alternative because of the very strong negative predictive value at around 97% for most patients for a select group of patients.

So what we've done is we set up our clinic flow to go through, look at our clinic cystoscopies. That's over almost over 100 procedures in about three weeks that we went through and essentially triaged. So anybody who was more than six months from their initial diagnosis or more than nine months from having a recurrent urothelial carcinoma diagnosis was identified and said, "Okay, what do you think?" We had our nurses and advanced practice providers contact the patient, go through what it meant to do the Cxbladder home test. Why I or my colleagues thought it was an important thing for them to consider doing and whether they would like to do it or reschedule their cystoscopy to when we were actually able to schedule procedures again. And so that led to a pretty nice workflow in terms of utilizing our nursing staff and advanced practice providers who are all working from home. So they were able to do this., communicate with our patients and make them feel like we're trying to do something to make sure that their bladder cancer care is taken care of in the midst of a lot of other uncertainty and anxiety.

And then also on the resulting end, know that if someone had a Cxbladder test that was concerning, meaning above the cutoff value, that we prioritize those patients to come in and get their cystoscopy. So we're really able to take our clinics into doing procedures and cystoscopies for the bladder cancer patients that we felt like most needed those. And that's how we sort of transitioned to this telemedicine workflow. When the result comes back, a video visit is scheduled with me and I get to video conference with the patient, talk to them about what has happened thus far with their bladder cancer care, what the Cxbladder result is, and how we're going to move forward in the future, what their next treatment schedule is going to be. And so that's how we've kind of operationalized this test and it's been wonderful thus far from patient experience and then our clinic experience as well.

Neal Shore: Thanks, Sima. That was a great overview. In the community where I am, we're really not too dissimilar. We've been having some patients come to the clinic and just pick up a kit and then we do our followup telemedicine review of the findings. And so, in order to be able to do this, there certainly has to be strong evidence of the value and as you say, the negative predictive value is particularly powerful in these tests and for different parts of the country depending upon where you are in terms of geographical barriers as well as a patients' fears and concerns. I know we're seeing a lot of that in the bladder cancer community, how they are getting prioritized as we are with all of our oncologic care.

And I think some of the silver lining during this pandemic has been to say, well how can we be innovative, safeguard our patients and safeguard our staff while at the same time providing the right amount of care and also the right amount of conversation and discussion, communication through telemedicine and optimizing the team approach, our advanced practice providers, our MAs, our RNs and all of the multidisciplinary team?

So, thank you, Sima. That was a great overview. And so lastly, Tom, if you could review how this one, two, three patient in-home sampling workflow could actually be real. They're more broadly adopted by different clinics.

Thomas Nifong: Sure. Thanks, Neal. I'd be happy to do that. And thank you, Sima, for giving really a nice overview of how you're using Cxbladder in your clinics right now. So the patient in-home self-sampling program really places the Cxbladder test into the urologic evaluation workflow in a manner that best allows you to make valuable clinical decisions based on the test results. So the program allows you to receive the test results without any physical interaction with the patient, which is particularly important right now with the COVID pandemic.

So, the in-home self-sampling program is a very simple process as shown here. It's three steps. As shown in step one, we only need two forms from you and you need to inform the patient that the test has been ordered. The required forms are the test requisition form and the statement of medical necessity. So, in fact, a clinic's face sheet that contains some or all of the information on our test requisition form can often take the place of some or even all of the information on these forms. So, the clinic sends us the forms, informs the patient, and then Pacific Edge takes it from there.

As shown in step two, we virtually hold the patient's hand through the entire process from sending the urine sampling system to the patient's home, walking them through the sample collection and then arranging sample pickup and shipment back to us. We also answer any and all questions on the reimbursement process. We then run the order test in our state of the art CLIA certified, CAP accredited laboratory and provide the result to you in four to five business days. Then it's up to you to follow up with the patient to review the results using your choice of tools, telemedicine, phone consultation or of course a face-to-face clinic visit.

Neal Shore: Well thanks, Tom. That was a very nice overview of how to get implementation started in the clinic, whether it's academic or community, metropolitan or rural, anywhere in the world frankly. So, if a practice, a clinic wants to get going, what are their next steps?

Thomas Nifong: Neal, they can call our team at 855-292-5237 or email us at and our Cxbladder assist team will be happy to help you.

Neal Shore: So thanks, Tom, and certainly folks listening in can get this information and figure out how it would best work for them and the patients that they take care of. Sima, thank you so much. I think these types of innovative results and innovative strategies are going to not only help us in this acute phase of this pandemic, but I think going forward we're going to see more remote-type testing, could be in the form of urine-based tests for cancer, for infections, and certainly even some remote blood testing. So making it all more efficient and safer for both patients and for healthcare providers. Thank you both very much.