Welcome to PathPulse, the Digital Diagnostic podcast! In this episode, “Precision at the Point of Diagnosis: The Role of Genomic Tests in Personalized Pathology,” host James Thackeray is joined by Jay Jhaveri to explore the transformative impact of genomic testing on modern diagnostics.
Jay Jhaveri is the Senior Director at Pacific Edge Cancer Diagnostics. His extensive background uniquely positions him at the intersection of clinical practice and diagnostic innovation. Jay earned his MD in 2006 and pursued a rich clinical and research path including general surgery, a fellowship in prostate cancer outcomes research at Weill Cornell, a men’s health fellowship, a Master’s of Public Health in epidemiology and biostatistics, a urology residency at UC Irvine, and a fellowship in clinical minimally invasive urologic surgery. He also became an associate-certified professional coder. Jay transitioned from clinical medicine to the industry, applying his deep medical knowledge to roles in medical affairs, clinical development, health economics, and outcomes research.
This episode delves into the shift from traditional pathology, which primarily focuses on the morphological examination of tissues, to precision pathology, which leverages genomic and transcriptomic signatures for personalized diagnoses. Jay Jhaveri explains how understanding specific genetic mutations and biomarkers can lead to more accurate risk stratification and tailored patient management. He highlights how genomic biomarker tests can help clinicians determine a patient’s risk of cancer, potentially reducing the need for invasive procedures and ensuring that high-risk patients receive prompt attention. Tune in to understand how genomic insights are reshaping the landscape of pathology and patient care.
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Transcript:
James Thackeray
All right. Well, hey, welcome to the PathPulse, the Digital Diagnostic podcast. This podcast showcases pioneers, innovators, and forward-thinking individuals within the digital pathology arena that are making a difference in day-to-day use, which we get excited about. These are pi-. These are true pioneers. I’m James Thackeray. I sit on the executive board for the Digital Diagnostic Summit. And in today’s episode, we will be exploring the topic of precision at the point of diagnosis, the role of genomic tests in personalized pathology with Jay Jhaveri.
We’re excited to have Jay on the podcast for the first time. I’ve worked with a number of his colleagues, and they have always spoken so highly of you Jay.
Why don’t you start by just giving us your background. It’ll be incredibly relevant. I read through it. It’s pretty incredible. But if you don’t mind, just give us the background of what you’ve been doing and where you started. That’d be great.
Jay Jhaveri
Well, thank you so much, James. I really appreciate the opportunity to be here. My name is Jay Jhaveri, and I’m the Senior Director at Pacific Edge Cancer Diagnostics, and I’ve had a various training background. So I’ll start where I began in my career, finished medical school, MD in 2006, and began in general surgery at New York Medical College, went on to do a fellowship in prostate cancer outcomes research at Weill Cornell Medical College, and then did a men’s health fellowship at the Maimonides Health Center, and also pursued a master’s of public health in epidemiology and biostatistics at that time.
Finally made my way to urology residency at the University of California Irvine and also completed a fellowship in clinical minimally invasive urologic surgery at the Henry Ford Health Systems. And after that, I also was able to become an associate certified professional coder. So I developed a better understanding of billing and coding. And I thought I was preparing myself for a career in academic surgery or at least clinical medicine, where a couple of different life events asked me to look at a different path and I started consulting for Big Pharma and industry where I started making a transition from clinical medicine and practicing seeing patients over to the industry side where all of the same skills that I learned on that side translated to fields like medical affairs, clinical development, health economics, outcomes research, publications, medical excellence, and launch excellence.
So that’s a little bit of a background about me. I’m sorry it’s kind of detailed.
James Thackeray
I love it and I’m always grateful that I don’t have to give my bio after something like that. So thank you, that was incredibly helpful and what a career thus far. That’s pretty exciting and I’m excited to kind of jump into this because there’s so much that you can tie from the clinical side to the development side and kind of just the overall where we’re at in precision medicine overall.
In general, as you know better than I do, we’ve been talking kind of about precision medicine for some years now. What does that really mean?
So if we were to start with kind of the basics and build up, how would you define precision pathology and how it differs from kind of traditional pathology? If we’re just to start with that basic of a foundation, how would you do that?
Jay Jhaveri
That’s a great question, James. And honestly, to begin there would be to begin with understanding traditional pathology and what that truly entails. So traditional pathology includes the surgical examination of any tissue that’s excised. First, gross specimen and then microscopic specimen. So what they do is they’ll remove, or the surgeons will remove whatever tissue they need and then they’ll stain it with different types of stains, dye it, and slice it under different conditions, maybe after freezing it in a paraffin block, and then take a microscope, microscopic evaluation of those cells and tissues, and come up with terms that are familiar with oncologic diagnosis or consistent with different oncologic diagnoses.
Typically they’ll name the architecture of the cells like adenocarcinoma or squamous cell or non-small cell lung. And then they’ll give a few different attributes about the tumor, but nothing specific to that individual and nothing specific to a particular genetic signature or a particular mutation that they may or may not harbor or anything that might be familial. Just basically a broad characterization of this is kind of the flavor and the variety of tumor and this is how aggressive it is.
They always have some indication of aggressive, no matter what type of tumor type it is, but they don’t know, let’s say, the actual address. They know the general vicinity. When you do the precision evaluation, you’re talking about evaluation of genetic transcriptomic signatures, the selection of specific genes, like CHEK2 or ATM, or pRB for prostate realm. And now it’s starting to enter the bladder realm as there have been so many different genetics, somatic and germline variations demonstrated that portend negative risk factors for the aggression in prostate cancer, that even now it’s starting to hit urothelial cancer and bladder cancer, which is a newer space.
And now we have mRNA urinary biomarkers, which is different than tissue and blood, which is evaluated in other areas. But now it’s even evaluated in the urine. And that can help us determine the risk of urothelial cancers, depending on the genetic signatures that we figure out.
So really, it’s been applied to a number of different tumors and it’s consistent with a number of different therapies. Either tumors prefer using an endocrine mechanism to drive their proliferation and growth, which is hormone-mediated in many types, like prostate and breast and ovarian, but then other tumors are kinase-mediated or protein-mediated, like kidney and liver and lung. So those are all different signatures associated with all of them.
And that’s really what they mean when they talk about personalized because they’ll talk about genetic signatures, genomics, mutations, and biomarkers that are also included with that, maybe companion diagnostics that are specific to a disease state or sub-state. But that’s basically how we separate the two. Does that all make sense?
James Thackeray
Yes, I mean, most of it, I mean, some of it’s past my pay grade, but I love it because I do think what we’re seeing, and tell me if I’m right here, we’ve seen that shift and it’s still shifting, right? I guess that would be my next question is where are we at with that total kind of change in, I would say, it’s in addition to, not taking away from anything, but going from just understanding the morphology of the tissue and the patient to this whole genomics, genetics, all these different things that you’ve just described.
Where are we at in that shift—of the mindset shift? Maybe from both, tell me both from the pathology side and then, obviously, from the clinical side—where the oncologists and the clinicians that are involved in that process, are we seeing that shift? Or I guess just give us an idea of how much that has shifted in the last few years from your perspective.
Jay Jhaveri
Absolutely, another relevant point. Well, with regard to pathologists and their understanding of specific triggering mutations and the presentation of aggressive or virulent sub phenotypes of disease, they have had the benefit of understanding what genetic mutations are capable of doing from a cellular standpoint where they might see hypertrophic cells or mucin or something else that the cells are secreting in the tumor specimen that we give them that is very much consistent with the pathology that is seen clinically.
So remember a pathologist doesn’t really see the patient. So they might get the history, that the patient is coughing up lots of different, you know, substance, and then you find out that they have a mucin-secreting tumor or that’s the case in the abdomen or something like that and then you figure out that, you know from a genetic standpoint, let’s say you’re able to do a genetic test on that, that it has specific genes that are known to secrete mucin, for example.
So those genes are driving the mucin production, which is driving the tumor production, which is what you clinically see. And then the pathologist sees it in the cell and then they call up the clinician and they verify the exact same story with a number of different observations. But the bottom line is it gives you the same clinical picture across different languages. The clinical language might be, you know, how much mucin they’re producing or how much they’re coughing up, you know, specific material, or how fast their heart rate is. But then in the pathologist, they’re evaluating a picture, a slide. So they’re giving you an understanding of that.
So in terms of that, their evolution has been quite rapid because this genetic testing and all of this, I would say it’s maybe 20 years old, and it started in different tumor types. Important to recognize that different tumor types are ahead of other ones and over this large timeline, we could call it maybe 25 years where it started really becoming mainstream, I would think that breast and lung were the leaders in this in terms of phenotypically and then genotypically trying to karyotype tumors. And then there were other ones that came afterwards, and this eventually came to prostate.
But the whole concept of genes driving tumors started around that time. And then we started finding specific drivers of tumors and then, you know, estrogen receptor and progesterone receptor, and ERPR positivity in breast and HER2 positivity and negativity is now basically a standard of care. If you’re triple negative breast, you handle that patient dramatically different than if you don’t. And that’s just the receptor status, that’s not a genotypic evaluation. That’s like the tip of the iceberg, so to speak.
So in prostate, eventually, it came to the fact that you’re able to evaluate that CHEK1 and CHEK2 and some of the tumors I mentioned before, pRB, TP53, if those mutations are there, those tumors tend to become very aggressive, like Gleason 9 or 10 disease or neuroendocrine or small cell differentiated. So really bad pathologies.
And now it’s finally entering the bladder cancer space and the thing that’s particularly exciting is that it can also be used for diagnostics. Like we mentioned that in circulating tumor DNA, you can use this in tumor tissue. But now the example that I’m going towards is CxBladder in Pacific Edge because we actually are able to evaluate urine specimens for urinary genomic transcriptomic signatures from mRNA proteins.
Those specific proteins are the homeobox A13 HOXA13, the Cyclin-dependent kinases CDK1 and CDK2, the MEK1 and MEK2, the CXCR2, which is a marker for inflammatory disease, and the IGFPP5, which is the insulin-like growth binding protein five.
So those five mRNA genetic signatures are known to be drivers of urothelial carcinoma, or the most common type of bladder cancer. Ninety-plus percent of bladder cancer patients are urothelial carcinoma patients. And that’s actually one of the new applications of some of these genetic genomic transcriptomic signatures.
And it’s actually particularly relevant today because I just got back from the American Neurological Association Meeting last week in Las Vegas, Nevada, where there was actually a plenary session dedicated to the new microhematuria guideline update, which was updated on February 27th of 2025, which now basically endorses urinary biomarker testing in the appropriately counseled risk stratified individual, usually an intermediate risk category.
Then those patients are actually counseled because the nature of these tests to figure out the specificity of how much their probability is of having cancer is to avoid unnecessary workup, unnecessary burden of travel, unnecessary procedures, and unnecessary medications that might be associated with those procedures. So there’s several downstream effects and, particularly for the CxBladder case, this is an avoidance of cystoscopy.
Cysto meaning bladder, scopie meaning to look inside. So to look inside the bladder. And that is the conventional or the traditional way to evaluate the skin on the inside of the bladder or the urothelium or the urothelial lining, a direct visualization to see if there are any tumors or anything, you know, abnormal inside that requires a biopsy or a resection.
And of course that’s uncomfortable for a patient because even though cameras are very small and the procedure only takes 2-3 minutes, it’s still uncomfortable having somebody have an instrument in the urethra and it’s a sensitive area. Many people have had infections there, for a male, the urethra is considerably longer than a female so the procedure lasts longer. It’s a little more uncomfortable. So people have anxiety about that kind of procedure. Some people require antibiotics after, other people have blood in the urine for several days after the procedure.
So there’s a lot of different dynamics that go into it, but this is one of the reasons why being able to urinate in a cup and being able to send a test somewhere and have a very strong negative predictive value test give you a guidance whether you actually need this much more uncomfortable invasive test. That’s essentially the nature of why we’re doing this and why the AUA did that plenary session.
James Thackeray
That’s awesome, and great example. I appreciate that. It’s great context. What, I guess from your perspective, what are the barriers to something like this? I mean, outside of maybe education, because especially something new like what you guys are doing now in bladder. So I know education is one of them, but are there other barriers to getting adoption?
Jay Jhaveri
Oh yeah, there are absolutely barriers always when it comes to clinical education, because, as you mentioned, you know, everybody’s at a different time point and a different adoption level, especially when you consider the United States, a country of 370 million people, there’s going to be a lot of variation where you go even within the same state sometimes. It’s definitely variation by geographies, Northwest versus Southeast per se, but there’s variation in a lot of the different practices.
So, as far as adoption, basically people look at what the guidelines are saying. And now that the guidelines have changed, this represents a transformational shift in the authorship of the guidelines, how they feel about urinary genomic testing, and then how all their recipients are going to feel about it subsequently, because they know that, let’s say the American Urological Association or the AUA is the authoritative body. I mean, who would know more about hematuria or bladder cancer or kidney cancer than them, other than maybe colleagues at the NCCN who also work in tight collaboration, the National Comprehensive Cancer Network. So it’s not like they work in silos. They’re very familiar with the different work.
But in the AUA, the most recent micro hematuria guideline revealed a Level A recommendation for the CxBladder triage test for the intermediate risk disease. And that Level A recommendation is the first time they ever mentioned something like this, because in 2012, guidelines were created in 2020, they started getting more risk stratified where they came up with a low intermediate and high risk grouping.
Then in 2024, they had another amendment with regard to risk factors.
But now, in 2025, not only did they change the low, high, and intermediate risk groups, they call the low risk group “low negligible.” And they changed around the factors for the intermediate risk group as well as the high so as to redistribute the population of patients across all three risk groups. And in the low negligible group, they’re not recommending any sort of invasive testing because the probability of that patient having cancer is less than 1%.
So they feel like a repeat urinalysis in 12 months with the renal ultrasound to try to figure out what the nature of disease was is a reasonable option. And if they have recurrent microhematuria, then you change the risk grouping and they might qualify this time for a urinary biomarker or a cystoscopy. And it’s basically just a very graduated risk-based approach over time, as opposed to just lumping all patients together, which has been happening for decades, where the microhematuria, the gross hematuria, and basically any time you’ve seen trace blood in the urine, a couple of cells, whatever, we’re getting a cystoscopy. You have to do this. It’s the way we do it. And now we’re getting away from that.
Again, there’s multiple tumor types and multiple examples I can give you for therapeutics that have done this and now it’s also entered the diagnostic realm. Even in the diagnostic realm, you’ve seen it in colon cancer and Cologaurd.
Our test is very similar in that respect, that if you have this blood in the urine and you’re going for a first time evaluation, we can give you a very thorough understanding of your risk for urothelial cancer using the CxBladder Triage Test.
Then, by the time you’re at your physician, you can use that to guide the discussion. If the physician sees that you have multiple different risk factors for urothelial cancer—if you have family history and you’ve been in the military and delivered Agent Orange in Vietnam and then worked in the painting business and been exposed to chemicals at the chemical factory then you know that’s someone who’s going to be and smoke cigarettes, you know, 100 cigarettes every five or six days then you know those are going to be really high-risk patients and you know, they’re going to be in a totally different risk group than someone who is 35 and has kidney stones, history of kidney stones, and leads a healthy life and has no exposures to radiations or chemicals and no family history of any sort of malignancy.
So that’s essentially how these things change and get adopted over time. And in bladder for urinary biomarker testing, I would say that we saw the inflection point in just the last couple of months and 2025 is when we’re going to see widespread adoption. And now we’re just working on the logistics, which you asked about before, barriers, logistics, insurance coverage, knowledge that, you know, physicians are aware of which tests to use, how to use them, ensuring that the logistics like kits not expiring are essentially fulfilled.
We rely very heavily on our commercial colleagues and our commercial staff to execute on all the relationships and, phenomenally for us and our company, they’re extremely, extremely skilled. So we tend not to have these logistical problems. Then also once you receive the samples, ensuring that they’re reported on in an appropriate time manner and in an area where you can interpret the result, because in laboratory testing, you can always get a non-interpretable result or the quality not sufficient or the quantity not sufficient of the tumor or something like that. So all of these are a reality when you do laboratory testing versus traditional pathology per se and genetic testing.
James Thackeray
That’s great. Thank you. That’s great. I was thinking about a couple different things as you were explaining that. One: guidelines, how important that is obviously, and congratulations to the success in that realm. You think of things like non-small cell lung cancer and biomarker testing in general with something like that, how far it’s come and how standard of care it is there, right?
And same, breast cancer, to your point, specific specialties have started, have maybe had more research and financial resources put into those early on and now we’re getting to some of these others, which is really exciting. And then the other thing that kind of stood out was logistically, you know, if I put my Lumea hat on, one of the things we’re always trying to figure out is yes, digital pathology, but the workflow of diagnostics, prognostics, biomarker testing, like how do we improve that?
And I, just to your point, I think what we’re trying to do is create a system that actually has access from the clinician, the lab, and the pathologist and then even downstream to companies like yours so that they’re all integrated into a system, which is which is easier to do in an academic center. Not easy there, but easier.
But now what we’re trying to do with you guys and other companies like yours is do that in the community space so we can develop the right workflow and make sure the test appropriately gets ordered at the appropriate time, or at least that they have the pathologist or the urologist or whoever is ordering has the access to do that order at the right time.
Jay Jhaveri
Yeah, absolutely. And what I was going to say, James, about that, is the one critical element that we’ve been working on with Lumea, and we’re very fortunate to be partnered with you, is the EMR integration workflow and pull through during the ordering because doctors are very much creatures of habit and they go through the same order forms consistently every day.
And frankly, where and how your pull down menu looks and how you click your favorites…I mean, everybody has these things. And if you’re an Epic chart user like I was, I used to have a favorite, everything favorite consult, favorite order set for a radical prostatectomy favorite, you know, treatment for whatever, it doesn’t matter because you can templatize all of your stuff.
So the faster we can integrate into the EMR and then the physicians can remember “this is how I get the test.” So in our use case scenario, the CxBladder test or the CxBladder triage test, ideally you wouldn’t have a several different fields where either you have to hit a search field and you have to like press the button that says CxBladder because then you have to use your brain and remember it. Ideally, it would be like a button across some of your favorite tests that you always order.
So if you order SMA, as, like, the metabolic panel and then CBC is the complete blood count. and liver function tests and all these things that you order commonly for pre-op or for urologist PSA and the creatinine, you know, if you order that separately or together.
So this would be a button like CxBladder, like hit that button right there. And, you know, that’s a urinary diagnostic test for all these patients with blood in the urine or patients, you know, if you’re talking about the monitor setting, those are patients who have already been diagnosed with bladder cancer, who are undergoing surveillance. So they have to have camera cystoscopy evaluation every 3 to 6 to 12 months depending on how far they are from their tumor resection and what type of tumor they have, what grade and stage they had.
So that monitor test can increase the interval because if you have one urinary test that says you’re negative, maybe we can skip the cystoscopy for that interval and bring you back six months later and then take a camera test because we don’t want to miss any bladder cancer. And if that’s negative, then bring you back later. And that way we reduce the unnecessary burden of procedures.
It’s important to note that we’ve seen this reduction in unnecessary testing burden of procedures repeatedly. So in the 2024 Journal of Urology publication STRATA paper, it revealed that the decrease in cystoscopy in that cohort was a 59% decrease in the utilization of unnecessary cystoscopy. And we also have data published from Kaiser Permanente colleagues in the Western Section of the AUA in 2024 that revealed a 77% decrease in the reduction of unnecessary cystoscopy and patients who don’t need that test anymore because they were able to use the triage test.
So these are some of the use cases and it improves the clinic workflow a lot because for patients who are positive, they get worked up a lot faster. We actually produced another abstract with our Kaiser Permanente colleagues for the AUA this year, the AUA 2025, and this one revealed that if they compared, they have something called the hematuria risk index, which is a score that they come up with based on the frequency of hematuria, the age, risk factors, things like that. And they compared it or contrasted it to the CxBladder Triage, which has been in use in the Kaiser Permanente system since 2021.
So they had thousands of patients, 3,353 patients, and did a propensity match one to one, looking at what happened to the CxBladder triage group against the Kaiser Permanente standard risk criteria group.
And basically the study revealed that in the low risk CxBladder triage group, very few people went on to get cystoscopy, maybe 3% of the population. And in the Kaiser group, and it was about 100 cystoscopy. In the Kaiser group, out of 1,240 patients, they had, sorry, 1,240 patients received cystoscopies. And in the low risk group, it was 46.5.
And in the high risk group, the patients who had the CxBladder Group had cystoscopy 75% of the time. So very frequent occurrence because they were high risk. And if you look at the Kaiser Standard of Care Group, it was about the same. They had 46% of the time. So there was no difference in the way that the Kaiser test was between the risk group categories and between the CxBladder low and the CxBladder high or the physician director protocol group, there were major differences.
And that’s basically what we know the test is designed to do—to risk stratify patients so that the patients who are high risk will come up and they end up in the clinic and you stratify them faster and they end up getting cystoscopy into URBT if that’s necessary. And if they’re low risk, tell them to avoid cystoscopy maybe for six months or a year. Or discuss it with them at least and see what they’re amenable to. And you figure it out clinically if that’s the best thing for you to do. And the urologist would have that discussion.
And for pathologists, the implication is for, basically, cytology. Pathologists always are interpreting cytology and adjudicating cytology is some challenging task. I’m glad I’m not a pathologist because it’s either negative, positive, or atypical. Atypical is very hard to figure out what that is. So a lot of physicians will use the CxBladder test based on a Konety, a Badrinath Konety et al, publication in 2019 that adjudicates atypical cytology.
So it’s another way to get another opinion because you look inside the bladder, you’re not really sure. You go to cytology, pathologist is not really sure, so let’s see what the Cxbladder test says and then figure out if we’re going to take you to the operating room and do some biopsies because now you’re high risk and we’re concerned about this versus us, the CxBladder is negative and you have low risk factor. So maybe we’ll hold off for another year or something like that.
James Thackeray
That’s great. And I think, yeah, the ability to try to set the appropriate triggers… So, for example, your atypical cytology example, if that sent a trigger to the pathologist that, hey, you may want to order this test based off of this, you know, what you’re getting back or… And set that upfront, that’s going to help in the workflow quite a bit, to make sure that the patients actually have access to this kind of testing.
This has been really…I don’t know, this has been great because it’s such a, it’s a perfect example of where things are going with precision pathology, precision medicine in general, because it’s, it really has more to do than just with pathology. It has to do with therapeutics downstream. This has been awesome. I’ve learned a ton. We’re going to have to do this again, because I probably could go, I think the both of us could go another hour on this topic easily,
But I really appreciate you joining us. We’re excited to be working with companies like yours and all the work that you guys are doing in the community with these type of tests. And so appreciate you joining us, Jay.
Jay Jhaveri
No problem. Thank you so much for the invitation and I look forward to the next interaction. Thank you.
