Rationale for the Use of Decipher RP Genomic Classifier to Inform Treatment - Ashley Ross

July 31, 2022

Alicia Morgans and Ashley Ross discuss Decipher RP genomic classifier for prostatectomy specimens, and how to integrate these tests into clinical practice. Decipher is a genomic classifier that looks at the whole genome and expression patterns on that genome. The genomic classifier score is a prognostic score that goes from 0 to 1, and it was first developed to stratify the risk of metastatic progression following prostatectomy.


Ashley Ross, MD, Ph.D., Associate Professor, Department of Urology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois

Alicia Morgans, MD, MPH, Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts

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Alicia Morgans: Hi, I'm so excited to be at ASCO 2022 with Dr. Ashley Ross of Northwestern University, where we had the opportunity to speak about decipher testing. Both Decipher biopsy and Decipher for prostatectomy specimens and how we integrate that into standard clinical practice. Thank you so much for being here.

Ashley Ross: Thank you for having me.

Alicia Morgans: Wonderful. So Ash, I know you've been involved with Decipher for a long time using it in clinical practice and actually working on a lot of trials and investigations to better understand how we use the data from the Decipher test to really inform our practice. Can you talk about the Decipher test as it was first developed for prostatectomy specimens and how you think about that in your practice?

Ashley Ross: Thank you again for having me and, of course. So Decipher is actually a Affymetrix 1.0 ST array, and they actually look at the whole genome and expression patterns on that genome. The genomic classifier score, which is the most studied and what we're used to seeing in our clinical reports, is a prognostic score that goes from zero to one, and it was first developed on risk of metastatic progression following prostatectomy.

Now, there's been over 30,000 patients with long-term outcomes that it's been studied in and across the board, it's shown to have independent prognostic ability for outcomes like prostate cancer specific mortality and metastasis. But as you've mentioned, the tool was first being used clinically in the post prostatectomy setting. And there we're looking at our patients and we're wondering particularly if they had adverse pathologic features, whether or not they need to have adjuvant radiation? Whether or not it can be early salvage radiation? And whether we should add a systemic therapy to that radiation?

Sometimes, if you're thinking just in general of adding systemic therapy in the post prostatectomy setting, it could also be a question that it depends on disease risk. So for a long time before the three clinical trials came out sort of differentiating early salvage and adjuvant radiation, the adjuvant question was very difficult and we were using Decipher risk to decide who needs that radiation before the PSA gets to 0.1 or 0.2. Even now with the publication of three randomized studies that have shown that early salvage radiation is probably equivalent to adjuvant, those studies were not representative of patients in the higher spectrum of disease risk. Seminal vesicle involvement, high Gleason grade. And so that's still a sweet spot for me to use Decipher.

So right now, when my patient has adverse pathologic features, I'll typically get a Decipher score and then I'll watch to see what the PSA does. I use ultrasensitive PSA. So I'm often looking at PSAs that are in the 0.01 0.02 range. If the Decipher score is high and there's one other feature that I find concerning high Gleason score, seminal vesicle involvement, then I usually will go and refer to the radiation oncologist before the PSA reaches 0.1. So even if it's 0.03, 0.04, I'll refer them in that scenario. If the Decipher score is lower, so this is lower than 0.6, I'll often wait till the PSA rises to about 0.1, 0.2, as long as they don't have a high Gleason score and seminal vesicle invasion.

The second way to use it. So one way of use is when do I pull the trigger on radiation? The second use is when we're going to do the radiation, do we add ADT or not? In the 9601 trial, which was the original trials looking at using bicalutamide in those cases for two years with radiation, they showed an overall survival benefit. But it was sort of limited to people who were being salvaged later. And when they did a sub-analysis of people with earlier PSAs, what they found was the benefit was strongest among people who had high Decipher scores.

So the genomics give you high risk adding the ADT or in that case, androgen receptor blockade with bicalutamide improved overall survival. But if you had low Decipher scores and you're doing salvage radiation plus the bicalutamide, you actually had a detriment to overall survival. Now, the sport trial just came out R2GO534, which basically showed that radiation to the prostate bed lymph nodes in six months of antigen deprivation therapy. In this case, it was an LHRH based therapy, seemed to have the best, at least progression free survival outcomes. And I'm still using Decipher to decide, am I going to add that ADT or not? So long winded answer, but two scenarios in the post prostatectomy setting.

 I'm using it to gauge, when am I doing my radiation? I think there's still a role for quote unquote adjuvant or let's call it early, early salvage before the PSA gets to 0.1. And the high Decipher teased me off to say, these are guys that I really want to put in that bucket. And then across the realm, whether I'm salvaging before the PSA gets to 0.1 or before the PSA gets to 0.5, do I add androgen deprivation therapy or not? High Decipher, I'm going to add it. Low Decipher, it's a really good look at the risk and benefits and understanding that I might be having a detriment to their overall survival and maybe I'm omitting the androgen deprivation therapy there.

Alicia Morgans: So those are really practical points and I'm glad that we raised them and that you really talk that through. And I also appreciate you talking us through these really nuts and bolts, concrete examples of how we can use these tests to do the right thing for our patients. It's extremely helpful.

Ashley Ross: Thank you.