Alicia Morgans: Hi. I'm so excited to be here with Jeff Tosoian, who is visiting us from Vanderbilt University where he is working on a PCF Young Investigator Award. Congratulations on your award, and thank you for being here.

Jeff Tosoian: Yes, of course. Thank you so much for having me.

Alicia Morgans: Wonderful. Well, can you tell us a little bit about what you're studying? I know you're really interested in trying to use minimally invasive tactics to understand how aggressive cancers can be, really thinking about a urine based approach, which is as minimally invasive as it gets for most people. So tell me a little bit about what you're working on.

Jeff Tosoian: Yeah, absolutely. So this has been a big multidisciplinary effort from day one, and we really sat down with the idea of, okay, we'd like to use today's technology in terms of sequencing and potential markers, but also keeping that end product in mind, being that it's not realistic to be able to sequence every patient cost-wise. And so you're sitting down with folks in a Arul Chinnaiyan's lab, mentors like Todd Morgan at the University of Michigan, Bruce Truck is mentor of mine from Hopkins, in epidemiology and biostatistics, kind of having all that input from the start. Yeah, we really we're looking to improve in that area of men with an elevated PSA who come in. And as you know, PSA is not a very, very specific test, and so we need something better there. And MRI is one option, and there are also six current biomarkers that are proposed as possibilities or considerations in that setting.

But none have really changed practice, in my opinion and so one of those markers, MPS, the my prostate score, one of the component markers came from my mentor, Arul's lab and so the idea was to build upon that with newer additional markers. And so we started with RNA seek data looking for novel markers, ended up identifying about 50 to 55 markers that were possible candidates for use, and took that to a PCR platform, ran that in a development cohort at the University of Michigan of almost 800 men who had undergone biopsy to develop a final model for higher grade cancers. And the unique thing about some of the markers that we found was that they are actually specifically expressed in higher grade prostate cancers. And that's unique relative to today's markers, which help us to identify and diagnose higher grade disease. But gram for gram, in terms of expression, are not truly specific for high grade prostate cancer, which as you know, that's what we need to be worried about.

That's what we're hoping to detect and treat. And so we developed a new model in the University of Michigan cohort, ended up finding that 17 of the 50, 55 markers contributed to independently some predictive ability. And so we have moved ahead with that into a validation cohort through the early detection research network that is completely separate from our development cohort and have tested the new model in that cohort and found it to offer some pretty substantial improvements over the currently existing NPS test, which as mentioned is one of our options currently. And so hopeful that this can really, really improve practice and help to avoid so many unnecessary biopsies and really identify those men that should undergo a biopsy and stand to benefit from that.

Alicia Morgans: Well, this is really just such an important area of research. I just want to emphasize some of the trials and tribulations that we as a prostate cancer community have been on over the last number of years. Some of that started with prostatectomies, and people with really low risk disease and then this of course evolved into the USPSTF, really making recommendations about PSA being potentially harmful or more importantly probably harmful was their initial recommendation. We've now evolved into a different space where we're thinking about using PSA with shared decision making, but our ability to identify in the least invasive way possible. Those cancers that are going to be a problem and that need treatment will I think really give us that important leap forward that we need to ensure that men are properly screened when it comes to their primary care, just annual visits and all of that. So this is something that is so important for our community, so important for our patients and I commend you for the work.

Jeff Tosoian: Well, thank you so much. Yeah, as you mentioned, it was so controversial whether or not screening should even be performed with PSA based on data from 10, 15 years ago. And so thankfully, one of my first mentors, Bill Carter at Hopkins, was one of the pioneers of active surveillance and would always say, PSA is not the problem, it's this coupling of a diagnosis to automatic treatment. And thankfully, we now know that many of the prostate cancers that would be detected don't need to be treated or certainly not treated initially and can be safely monitored. And so having started my research in inactive surveillance and now moving more into biomarkers, of course it all goes together. And end goal is just being able to serve our patients better with non-invasive, yet highly accurate tests that can take this practice of PSA screening and prostate cancer diagnosis from what is a little bit abstract right now to a more clear approach. If this is found, here's our next step and all these steps, of course, being guided by good evidence.

Alicia Morgans: Wonderful. Well, what can we in the PCF community expect from you and your team in the next year, I think you have another year left on your grant, right?

Jeff Tosoian: Yes, yes, yes. And so we'll be finishing up the validation in the elevated PSA cohort, the men with a PSA of three to 10. And then we'll, assuming all checks out as it appears to be, we'll move into additional spaces and so our next step is looking in the active surveillance population who of course already have a diagnosis of cancer, but there's hope that with this new panel, which now incorporates markers specific for high grade cancer that actually can help differentiate active surveillance patients with higher risk disease from those that are appropriate for surveillance. And a subsequent step will be, of course, looking in the African American population, which has been higher risk for several reasons, but is known to often harbor different mutations in their prostate cancer tumors. And that of course has a role in what we then see expressed in the urine and in the markers. And so to ensure that we're serving all patients well, we have planned an additional validation and if necessary, new development and validation specifically in the African American population as well.

Alicia Morgans: Wonderful. Well, no small task, but some really, really important work. So keep up the good work and we certainly will be keeping an eye out for what you bring to the table in the future, and I'm sure it will be some wonderful things so thank you so much for your efforts and for your time today.

Jeff Tosoian: Thank you. Really appreciate it.