Daniel Keizman: Thank you for inviting me.
Zachary Klaassen: So, before we get into your work, let's just level set about how Decipher informs NCCN how it reclassifies it.
Daniel Keizman: So, we know that with prostate cancer, actually, most of the patient with prostate cancer, we usually do a clinical pathologic risk stratification based on the PSA clinical stage, Gleason score, number of positive cores. And this convenient model, let's say the NCCN model, has a wide heterogeneity. So it can underscore in terms of risk aggressive tumors and overscore in terms of risk indolent tumor, and then lead to overtreatment or undertreatment. So, probably, we need better tools. And as discussed per different guidelines, Decipher genomic test is one of these great tools.
Zachary Klaassen: Yeah, absolutely. And it's been validated and it's in the guidelines now. From the study design, just walk our listeners through what you guys did for the ASCO presentation.
Daniel Keizman: So we are doing a lot of Deciphers. So, among all the patient with prostate cancer, we took only the early prostate cancer for which we had both the clinical parameters and the Decipher and the whole transcriptomic data degree, and then we analyzed this patient in terms of, number one, how is the Decipher behaving in non-American population.
Zachary Klaassen: Sure.
Daniel Keizman: Because actually, the vast majority of the data is from American patient. We have almost no data from non-American patient. And it's always a question, "Can you extrapolate the data from one region to another region?"
Zachary Klaassen: Yeah, absolutely.
Daniel Keizman: And then we wanted to see how patient that reclassified according to the Decipher. Let's say a low-risk NCCN going to be high-risk with Decipher, what's their GRID profile versus those that stayed in the same risk?
Zachary Klaassen: Right. No, it's a great background and really some interesting results. Just walk our listeners through the molecular signatures you guys found through the study.
Daniel Keizman: So, what we saw is, first, that, in non-American population, the Decipher leads to a significant proportion of patient having another risk, other high-risk or down risk. So this was the first aim. And then, in patient that had the higher risk versus those that stayed in the same risk or had a lower risk, then there was a significant change in the transcriptomic profile, the GRID profile in terms of proliferation, and this is HR activity, AR activity, PTEN loss, TP53 inactive, and RB inactivity.
Zachary Klaassen: Yeah. Great summary. I think we know Decipher works. We know it reclassifies NCCN. Why is it important to understand the transcriptomic aspect?
Daniel Keizman: Yeah. So, probably, also in the Decipher, that the algorithm will take only 22 RNA markers, but then we have, for research purposes, the whole transcriptome, the GRID. Then, probably, also within the Decipher, we can find different population. So, I always look at the GRID. And let's say I have a patient with low-risk NCCN, low-risk Decipher, but a high-risk GRID per molecular feature. I will always say, "We should consider maybe to intensify the therapy despite having a usual low-risk."
Zachary Klaassen: Interesting, yeah. So it's not just taking the score, but looking deeper under the hood at the GRID analysis. Interesting. Anything we haven't hit on? Any summary points for our listeners?
Daniel Keizman: Yeah. So, number one, I think that, as a physician, it's always a problem because, worldwide, in most of the countries, Decipher is not covered nationally. So patient have to pay out of pocket, and it's always a dilemma should you make the patient spend a lot of money. But I think that, with Decipher, I feel confident we do it a lot. Because if you can de-intensify the therapy, it means a lot to the patient. So I think that I feel now more confident in recommending the patient to spend out of pocket to do the test. And number two, I think that, when you have a stronger biologic basis to explain what you see clinically, again, it gives you more confident about the test.
Zachary Klaassen: Yeah. Great summary. Congratulations on the great work.
Daniel Keizman: Thank you.
Zachary Klaassen: I think this is really taking a test that we know works and learning more about it and why it happens. So, thank you for joining us on UroToday.
Daniel Keizman: Thank you very much for inviting me.