Hi, I am Todd Cohen, MD. I am the Vice President of Medical Affairs and Medical Director of Urology for Myriad Genetics. I would like to discuss Abstract 195 that was recently presented at the 2021 ASCO Genitourinary Symposium.

This abstract was designed, or the study was designed, to revalidate a finding that was recently published which established a threshold for men with prostate cancer, using the Prolaris genomic expression classifier.

What this threshold showed was that men could be identified based on the aggressiveness of their disease who require some type of treatment for their prostate cancer. What the threshold did was isolate men that had a higher or lower risk of developing metastatic disease within a 10-year period.

This was metastatic disease that occurred after some form of treatment, whether it be surgical treatment or radiation therapy. What the threshold showed is that, below a certain point on the Prolaris test, that the risk of developing metastatic disease was significantly lower, despite what kind of treatment was done.

In other words, if their therapy was intensified, they had no real change in their risk of metastatic disease, but men above this threshold had a much higher risk of developing metastatic disease and benefited from intensification of their treatment.

The second study, which was presented just recently at the ASCO GU meeting, really went on to validate in more modern terms of treatment by radiation therapy this threshold. What it looked at specifically was men that had experienced modern dosing for radiation with or without hormonal therapy.

This hormonal therapy was broken into what we call patients that had sufficient hormonal therapy or that their amount of therapy that they had, or the duration of the therapy, was consistent with the NCCN guidelines, and men also that had insufficient therapy from ADT, as well as men that had no androgen deprivation or ADT.

The reason why this was separated out that way is because it really signifies a true, realistic cohort of men, men that really exist in the real world. A lot of men do not tolerate hormone therapy, and they go off of it for one reason or another, while some men do maintain the entire course of hormone therapy. It was a really realistic look at a cohort of men undergoing radiation therapy.

What was discovered is that, using the threshold as determined by the previous study in Prolaris, that men below this threshold, whether they had androgen deprivation therapy, the sufficient amount or an insufficient amount, or actually did not even have androgen deprivation therapy, that their risk of developing metastasis after treatment was very low.

That they showed no significant benefit from having any form of additional androgen deprivation on top of the radiation. Contrary to this, men above this threshold showed a significant improvement in the risk of developing metastatic disease after radiation when they were treated with androgen deprivation therapy.

It was able to dichotomize men into the two groups. The group where the risk of the metastasis was significantly low and the risk of men that was significantly high. In the low-risk, it was not that they did not have any absolute benefit from androgen deprivation therapy.

The study showed that the benefit was so slight that the morbidity that is incurred by having androgen deprivation therapy may actually be worse in the long run than the benefit that the men got from having androgen deprivation.

As the Prolaris test showed that there was decreasing aggressiveness of the disease, there was less absolute benefit than adding androgen deprivation therapy. In contrast to that, as the Prolaris test showed, that men above the preordained threshold, and as they got even further to the more aggressive side of this threshold, they saw an increasing benefit of intensification of their treatment.

What we showed was that adding androgen deprivation therapy in the more aggressive men, regardless of their NCCN risk category, that these men had an absolute significant, both clinically and statistically, benefit of adding intensification to their treatment by the use of androgen deprivation therapy.

Again, in contrast, the men below that, the absolute benefit of adding androgen deprivation therapy was significantly diminished, to the point where the risk of adding androgen deprivation for the morbidities which include everything from fatigue and sexual side effects, to the possibility of coronary vascular disease, to bone problems, and just quality of life, was not worth adding a slight improvement in the risk of developing metastasis.

That is something that has to be individualized. If a patient, for example, has a 1% absolute benefit in the decrease in the risk of developing metastasis after treatment by adding androgen deprivation therapy, is it worth taking six months to upwards of three years of this medication, with all the potential morbidities and side effects associated with it?

That is something that the doctor, the treating physician, can sit down with the patient and have that discussion. Obviously, if they are above the threshold, and there is a significant both clinical, and from a statistical standpoint, a statistically significant benefit, then it is more likely that the patient would want to go on the additional therapy to improve his long-term oncologic outcomes.