Investigators link genomic and clinical data to real-world outcomes in prostate cancer

In this interview, Michael S. Leapman, MD, MHS, and Preston C. Sprenkle, MD, discuss the study, “Development of a Longitudinal Prostate Cancer Transcriptomic and Clinical Data Linkage,”1 for which they served as the lead and senior authors, respectively. Leapman is a urologic oncologist, a prostate cancer clinician, and an associate professor of urology at Yale University School of Medicine, and Sprenkle is a urologic oncologist and an associate professor of urology at Yale University School of Medicine in New Haven, Connecticut.

This transcription has been edited for clarity.

Could you discuss the background and rationale for this study?

Michael S. Leapman, MD, MHS

Leapman: The big picture for this study is that we worked with Veracyte, which is the maker of the Decipher Genomic Profile Test, to begin to understand real-world use of the Decipher Classifier. We teamed up to look at all evidence of Decipher testing based on the centralized records they keep. This is really our first effort to begin to develop a way to understand what happens in the real-world setting. We linked Decipher test results and clinical information with real-world outcomes to begin to understand the key end points in prostate cancer, such as recurrence and metastasis following treatment.

What were the key findings from this study?

Leapman: The key findings of this study were that we were able to successfully link over 92,000 individuals who had evidence of Decipher testing with real-world clinical data. The scale of that linkage and the manner with which we were able to do it is really exciting and opens the door for a lot of future discovery. Some of the other findings that are new and notable are that we have to pare that number down when we want to look at certain outcomes. Some individuals are more or less active in the real-world data; they have more or less activity in terms of claims that allow us to identify the downstream outcomes. When we start paring it down to about 58,000 patients who have regular activity in claims, we can identify the metastasis and recurrence outcomes in those individuals and also look based on biopsy-tested and radical prostatectomy-tested samples.

What are the implications of these findings?

Leapman: The first step is to begin to look at prognostic associations. We have a publication that should be coming out shortly, and this work has been presented at the [American Urological Association annual] meeting previously, where we looked at, in the real-world setting, in patients who are actually tested as part of their clinical care, are Decipher results associated with those key outcomes, recurrence and metastasis? What we have found is that in both the biopsy- and prostatectomy-tested patients, Decipher was an independent risk factor for developing recurrence or metastasis over time. That's the first step is validating the prognostic association of the test and the clinical outcome.

Preston C. Sprenkle, MD

Sprenkle: The importance of that, too, is that the test was designed in a retrospective cohort. So, they saw that the Decipher test worked by finding people who had certain outcomes, and then seeing what treatment they had gotten in testing their tissue from 10 years previously. This is unique, because this is the first time where people had the test, they then had treatment after the test was done, as Dr. Leapman has mentioned, in the real-world setting. So, this is a true validation in long-term follow-up of people who had to test prospectively, and then were treated. It's a very powerful, unique outcome to be able to talk about.

What future work is planned based on this study?

Leapman: We have another publication in process that is looking at those outcomes. This first paper that we're talking about was really talking about the nuts and bolts of how we are assessing those outcomes. Believe it or not, there's a ton of work that goes into that, because if we believe that a certain outcome happened, we want to be confident that it did indeed occur. The next step is to begin looking at clinical outcomes, those recurrence and metastasis and progression events. I think the next phase of discovery is understanding, are there new signatures? Are there new molecular features that we were unable to detect in smaller cohorts that we are able to appreciate at the larger level? As an additional layer, to begin understanding what happened clinically, as a consequence or as a function of having a Decipher test––were differences in management appreciable? Did patients who had a high Decipher test after their prostatectomy get adjuvant radiation? Were patients enrolled in active surveillance? In patient who had high scores, did they get treated? Did they progress faster? There are numerous very practical clinical questions that can be unpacked with a resource like this.

What has been the impact of genomic testing in prostate cancer management? What influence will it continue to have moving forward?

Sprenkle: It is integrated into our clinical practice, and it has been shown, in multiple studies, to influence how a clinician treats patients. So, it changes our practice. Based on the results, we're changing our practice. But this was one of the first studies to show that those changes actually make a difference in clinical outcomes in a broad sense. We need to look at that more specifically. That's one of the many possibilities of things that need to be done still. In prostate cancer, we're about a decade behind the breast cancer literature in their use of genomics. In breast cancer, based on certain gene signatures, different treatments are recommended. It's very specific; [this is the] best treatment for this gene signature. We're not at that point yet, but that's really the goal. There should be and we're on our way to identifying that; there's a very bright future for genomics in prostate cancer management. We're right at the cusp of being able to clarify who are those patients that benefit from certain types of management? This study is one of the major steps in that direction to help us start to identify that.

Reference

1. Leapman MS, Ho J, Liu Y, et al. Development of a longitudinal prostate cancer transcriptomic and clinical data linkage. JAMA Netw Open. 2024;7(6):e2417274. doi:10.1001/jamanetworkopen.2024.17274