Prostate Cancer Markers: Challenges in Differentiating Low-Risk Cases "Discussion"
July 24, 2024
At the CAncer or Not Cancer: Evaluating and Reconsidering GG1 prostate cancer (CANCER-GG1?) Symposium, experts debate the effectiveness of biomarkers in distinguishing between different grades of prostate cancer, particularly in active surveillance cohorts. The conversation highlights the difficulty in identifying the small percentage of high-risk patients within low-risk cohorts. The discussion concludes with an observation that some markers may show promise in predicting higher-grade cancers, but such events are rare in low-risk cohorts.
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Read the Full Video Transcript
Speaker 1: I would take one nail out of the coffin of the markers, not that they should be used all the time. But part of the problem is that all the studies have tried to separate 3+3 from 3+4. And the vast majority of 3+4 in these surveillance cohorts are low volumes of use [inaudible 00:00:16] subtype [inaudible 00:00:17] which we've been talking about is [inaudible 00:00:18] more than anything else. So, you're asking the marker to separate apples from apples, which is a biological possibility. So—
Speaker 2: What broke me was that I was sure Decipher was going to work with the second. I really was. And you either... it's the endpoint.
Speaker 1: I actually really think—
Speaker 2: Decipher and CSF cohort, that just did it.
Speaker 1: I am optimistic when this finally gets done in CANARY with one, and in our [inaudible 00:00:43] studies with longer-term follow-up to patients that acute [inaudible 00:00:45] surveillance, which is a much smaller subset. I expect variances. But you're not trying to find the 30-40% patients, you're trying to find the 2-5% of patients who [inaudible 00:00:55]. Which is a much harder ask. And it's a harder cost-effectiveness [inaudible 00:00:59], too.
Speaker 2: I'll put a nail back in the coffin. Ten years ago, I did that study with POLARIS, but I was too young and naïve to make sure that they agreed to publish it. They squashed it, so [inaudible 00:01:08].
Speaker 1: Oh, really.
Speaker 2: So theirs didn't work either.
Speaker 3: May I suggest something?
Speaker 1: Yeah, please.
Speaker 3: It might not be the problem with the marker, it may actually be the endpoint.
Speaker 1: Yes.
Speaker 3: That a small change in a small part of the tumor for a large or higher grade is actually not that significant, as evidenced by the fact that the marker doesn't change that much, right? And that relates to something that Andrew has brought up many times, which is, and goes back to his point about what's the real endpoint here? A small change in grade that's on the incidence of Gleason grade of 2 against the context of a mostly or historically Gleason 3, that the clinical significance of that small amount of grade group 4 is actually not 100% clear.
Speaker 2: To mirror your point and Matt's point, the study that I was involved with, there did appear to be a signal for predicting 4+3, there just weren't enough events because it's a low-risk cohort.
Speaker 3: Okay.
Speaker 1: That was right—
Speaker 1: I would take one nail out of the coffin of the markers, not that they should be used all the time. But part of the problem is that all the studies have tried to separate 3+3 from 3+4. And the vast majority of 3+4 in these surveillance cohorts are low volumes of use [inaudible 00:00:16] subtype [inaudible 00:00:17] which we've been talking about is [inaudible 00:00:18] more than anything else. So, you're asking the marker to separate apples from apples, which is a biological possibility. So—
Speaker 2: What broke me was that I was sure Decipher was going to work with the second. I really was. And you either... it's the endpoint.
Speaker 1: I actually really think—
Speaker 2: Decipher and CSF cohort, that just did it.
Speaker 1: I am optimistic when this finally gets done in CANARY with one, and in our [inaudible 00:00:43] studies with longer-term follow-up to patients that acute [inaudible 00:00:45] surveillance, which is a much smaller subset. I expect variances. But you're not trying to find the 30-40% patients, you're trying to find the 2-5% of patients who [inaudible 00:00:55]. Which is a much harder ask. And it's a harder cost-effectiveness [inaudible 00:00:59], too.
Speaker 2: I'll put a nail back in the coffin. Ten years ago, I did that study with POLARIS, but I was too young and naïve to make sure that they agreed to publish it. They squashed it, so [inaudible 00:01:08].
Speaker 1: Oh, really.
Speaker 2: So theirs didn't work either.
Speaker 3: May I suggest something?
Speaker 1: Yeah, please.
Speaker 3: It might not be the problem with the marker, it may actually be the endpoint.
Speaker 1: Yes.
Speaker 3: That a small change in a small part of the tumor for a large or higher grade is actually not that significant, as evidenced by the fact that the marker doesn't change that much, right? And that relates to something that Andrew has brought up many times, which is, and goes back to his point about what's the real endpoint here? A small change in grade that's on the incidence of Gleason grade of 2 against the context of a mostly or historically Gleason 3, that the clinical significance of that small amount of grade group 4 is actually not 100% clear.
Speaker 2: To mirror your point and Matt's point, the study that I was involved with, there did appear to be a signal for predicting 4+3, there just weren't enough events because it's a low-risk cohort.
Speaker 3: Okay.
Speaker 1: That was right—