Joshua Lang: Thanks so much for having me.
Zachary Klaassen: You had the difficult task of discussing four abstracts and we're going to group the first two together because they have the commonality of varicites. So maybe just go through those two abstracts and your thoughts on those.
Joshua Lang: Absolutely. Well, we face these very important clinical challenges of when patients present with either locally advanced prostate cancer or newly diagnosed metastatic prostate cancer, what's the best way to optimize therapies for those patients? Is it single agent hormonal therapy? Is it combination hormonal therapy? In some situations, these are patients, especially in the metastatic setting where we think about adding docetaxel, that idea that triplet therapy could be more effective for those very high-risk situations. The challenge though is how do we identify which patient is going to be appropriate for those different therapies? Again, just given the toxicities that come along with them.
So that's where these abstracts were really focused in trying to better identify patients at higher risk for developing lethal metastatic prostate cancer or treatment resistant prostate cancer. So in the first study, they were focused in that space asking, well, can we try to identify high versus low Decipher scores that might associate with a greater likelihood of developing metastatic disease? So they used samples from four different clinical trials in radiation oncology, combining radiation with different types of chemotherapy and asked, is the Decipher score prognostic? And what they were able to show is that it was in fact prognostic in those studies for again, risk of a recurrent prostate cancer.
Zachary Klaassen: Right. And then the second study was looking at Enzalutamide with ADT plus or minus docetaxel. What were the findings in that presented by Dr. Sweeney?
Joshua Lang: Yeah, so a couple of major findings came out of that study that again, also I think they demonstrated and really confirmed the prognostic utility of the Decipher score and wherein a high Decipher score associates with a greater chance of developing resistance or death when treated with ADT and Enzalutamide alone.
Zachary Klaassen: I see.
Joshua Lang: And then some evidence for patients with high volume disease, and this is on conventional imaging, not PET scans, from conventional imaging, those patients with a high Decipher score appear to have a greater benefit from the addition of docetaxel.
Zachary Klaassen: So we've had decipher for a while now. We've seen it in radiation oncology clinics, urology clinics. It's now coming into the medical oncology realm and sort of advanced prostate. What are your thoughts on how this moves forward for Decipher?
Joshua Lang: I think there's two things that are really important to remember. The first is that the genomic classifiers are not genetic tests. It's still critical that we do germline and somatic tumor genetic testing.
Zachary Klaassen: Well said.
Joshua Lang: And this is where after tumor genetic testing, that's when we can ask, do these genomic classifiers asking with gene expression studies, do we see cancers that have a higher proliferation rate? Or again, ones that are more metabolically active and more likely to become resistant sooner or metastasize earlier? So that's what Decipher's doing and I think that's the additive benefit. And again, gives us more information to say in our risk stratification, how do we think about the person sitting in front of us today? It doesn't predict yet though. And I think this is where there's some trials that are coming up that will help really define does it predict benefit from therapeutic intensification? So new studies coming up, hopefully in the next couple of years we'll get those readouts. But that's I think where that decipher test is showing clinical utility more to come though.
Zachary Klaassen: Yeah. And I think I'm glad you made that point because this is not somatic testing, this is not germline. Still do that. This is an additive to see if we can figure out who's going to benefit.
Joshua Lang: Exactly.
Zachary Klaassen: Third trial was clinical transcriptomics and looking at an old trial charted spatial transcriptomics, that's very interesting. An old trial, new technology. What are your thoughts on that? What were the results?
Joshua Lang: It's a really exciting time in oncology research right now. Being able to ask, not only can we compare what we get with these transcriptional analyses, but how do we match it to those H&E slides that we got on every single patient biopsy that's performed? And can those two dots be connected? So with the novel AI algorithm, the investigators were able to identify a signature from the gene expression analysis that correlates with an H&E signature. And then they asked, "Okay, how do we expand this and see is there clinical utility?" Now they trained their classifier using patients who had received hormonal therapy alone from the charted study and then asked, did it associate with the benefit from addition of docetaxel? And they did show some prognostic relevance, some limitations in terms of the study and challenges just that we don't use ADT docetaxel as the standard of care now, but I think shows a potential utility for these new AI-based algorithms to analyze H&E slides.
Zachary Klaassen: Yeah, absolutely. I mean, we think about how this could be trained on all the other studies since charted. The technology's really exciting, isn't it?
Joshua Lang: It really is. Again, this is the most exciting time in cancer research ever.
Zachary Klaassen: No question.
Joshua Lang: So I think our hope is that as these models are trained, then how do we validate them? But then we've got to get that next step into that prospective trial and say, does it really predict benefit or not? So exciting times I think in the future of biomarker clinical trials.
Zachary Klaassen: No question. Last but certainly not least, the SWOG trial looking at miRNA in patients with clinical stage one testis cancer predicting early recurrence. I mean SWOG cooperative group, huge trial. What were your initial thoughts from that data and what are your thoughts on that going forward?
Joshua Lang: Three things. I think the first is kudos to the investigators for developing an analytically validated assay, meaning that they know how well this assay performs. They know how reproducible it is from patient to patient and time point to time point. So that gives them this incredible opportunity to then move into clinical trials, which is exactly what they showed in terms of their first clinical study looking at low, intermediate, and high risk, getting a baseline sample before patients enters surveillance and then doing the longitudinal follow-up and monitoring and correlating that with radiographic recurrence. It's great trial design with a great biomarker and some very exciting specificity for the biomarker.
The sensitivity is still low at baseline, but very encouraged in their interim analysis in terms of the specificity, the positive predictive value, and the negative predictive value as well. So as the study completes and matures, I think that's where there'll be more data, hopefully presented later this year about that assay.
Zachary Klaassen: Super exciting. I think for our testis cancer patients, knowing who's at risk of recurrence, because we know most of these patients won't recur, but you want to see if we can predict who's going to recur. I think it's a fascinating and a huge, huge lift by that team.
Joshua Lang: It absolutely is. And again, we have to do better than the serum biomarkers we've been using for the last 40 years.
Zachary Klaassen: Right, exactly.
Joshua Lang: And this I think is the clearest opportunity to do that.
Zachary Klaassen: No question. Phenomenal conversation. Congrats on a great discussion at ASCO. Anything we haven't hit on? Any take home messages for our listeners?
Joshua Lang: I think the biggest take home message is that the more we understand about the biology of our patient's disease, the better we'll do in terms of how to intensify therapies. And we have so many new treatments that are also in the pipeline, especially for men who present with locally advanced disease, but also metastatic disease. Now our next step is really to understand who benefits the most, but also who are those patients we can de-intensify therapy on and spare them some of those side effects while still maintaining our ability to cure them.
Zachary Klaassen: Yeah. Well said, Josh. Thanks so much for joining us on UroToday.
Joshua Lang: Thanks so much.