Dr Tward Discusses CCR Scores Accurately Guiding Treatment for Prostate Cancer

Summarizing data presented at the 2021 Virtual ASCO Genitourinary Cancers Symposium, Jonathan Tward, MD, Huntsman Cancer Institute, University of Utah, discusses how the link between clinical cell-cycle risk score and metastasis after radiation therapy can be used to identify patients with prostate cancer eligible to forgo combined androgen deprivation therapy (ADT).

Transcript

My name is Dr. Jonathan Tward and I am the leader of the Huntsman Cancer Institute at the University of Utah Genitourinary Cancer Center. I am a professor of radiation oncology.

It is a pleasure to share with you our current study that we presented recently at the GU Cancer Symposium.

What we were trying to investigate is whether or not there were men who were diagnosed with localized prostate cancer who fall into the NCCN intermediate- or high-risk groups who could consider using radiation alone, as opposed to the Guideline recommended combination therapy of radiation plus androgen deprivation therapy.

The NCCN Guidelines recommend that men with unfavorable intermediate-risk and high-risk prostate cancer always combine radiation therapy with at least 4 months or 18 months of radiation therapy, respectively, for those risk groups.

We had a hunch that we might be over-treating some men in that group with the unnecessary morbidity that comes along with the androgen deprivation therapy.

I was interested in using the commercially available Prolaris test, which was already being used to discriminate which men with more favorable localized prostate cancer could safely go on active surveillance, but I had a hunch that it might be used as an excellent predictor of metastasis and a discriminator of who does or doesn't benefit from ADT.

In a prior development work, we pre-specified a threshold score which is combining some of the molecular information from the cell cycle progression gene test that the Prolaris does, along with the clinical factors that people routinely use to risk stratify, such as the age, the Gleason score, the percent positive cores, etc.

Using this combined molecular and clinical factor risk model we were able to evaluate in a development study if a score threshold prognosticated a risk of metastasis that was so low over the next 10 years after treatment that maybe men could forgo doing combined modality therapies.

In that development study, which was just recently published in Clinical Genitourinary Cancer, we found that whether you had surgical removal of the prostate or radiation therapy of the prostate below this threshold score, the risk of metastasis did not exceed five% at 10 years.

We used that score threshold into this additional validation study to ask the very specific question, if men undergoing dose escalated radiation therapy with modern techniques could consider foregoing using it with ADT, as well.

In the current study, we looked at this in 741 men. Approximately half of the men in the study had androgen deprivation therapy with the radiation and the other half did not.

What we found was that, like the development study, it was an excellent prognosticator of metastasis. Furthermore, the relative benefit of adding androgen deprivation therapy, on top of radiation therapy, didn't seem to make a lot of clinical sense in this population.

At the end of the day, what we were able to do is stratify men by being below this threshold and above this threshold. Above the threshold men have approximately 25% risk of metastasis over 10 years, below the threshold approximately four percent risk of metastasis.

As I stated before, the relative risk reduction of using androgen deprivation therapy with radiation did not drive this metastasis down in a way that would be meaningful to most patients.

What we can do with the Prolaris test now is give an extremely precise and accurate risk estimate of an individual's risk of metastasis after radiation therapy. Then physicians and their patients can have a very well-informed discussion on whether or not they think that the relative benefit of adding ADT into radiation therapies makes sense for them for the relatively low absolute benefit that you would see for men below this threshold.

If you look at the percentage of men that would be affected, this study implies that half of the men who are diagnosed with unfavorable intermediate-risk prostate cancer each year could probably avoid combination therapies, and about 20% of men with high-risk prostate cancer could avoid combination therapies.

This is a very significant percentage of men who, across the world, could be safely treated with radiation monotherapy alone for these risk groups and avoid all the unnecessary morbidities and complications that one would expect with androgen deprivation therapy.