An Interview with Dr. Jonathan D. Tward: Applying Prognostic Genomic Testing to Guide Prostate Cancer Treatment

DURING THE 2021 ASCO Genitourinary Cancers Symposium, Jonathan D. Tward, MD, PhD, Professor of Radiation Oncology at the Huntsman Cancer Institute, University of Utah, presented the results of a study that demonstrated the prognostic value of the Prolaris® genomic test (Myriad Genetics, Inc, Salt Lake City, UT) in helping guide prostate cancer treatment, so that certain patients may potentially avoid more aggressive therapy. The Polaris® test measures average RNA expression levels of 31 cell-cycle proliferation (CCP) genes and 15 control or reference genes, from which it generates a CCP score that when combined with clinical risk factors can predict the risk of metastasis after undergoing surgery or radiation therapy, or the risk of death from prostate cancer in a conservatively managed population.

GU Oncology Now spoke with Dr. Tward about the results of the study, “Association of the clinical cell-cycle risk score with metastasis after radiation therapy and identification of men with prostate cancer who can forgo combined androgen deprivation therapy (ADT)” (Abstract 195). In this retrospective study, the CCP score from the Prolaris test was combined with traditional clinical risk factors to obtain the combined clinical and cell-cycle risk (CCR) score in order to determine the 10-year risk of metastasis in patients with National Comprehensive Cancer Network (NCCN) intermediate or high-risk localized prostate cancer. The CCR score was found to be a highly precise and accurate predictor of metastasis in these patients whether or not they also received ADT.

GU Oncology Now: What are the key takeaways from the study?

Dr. Tward: The key takeaways are that a commercially available test can give men diagnosed with localized prostate cancer a highly precise and accurate estimate of their risk of metastasis after undergoing radiation therapy. This information can be used by the patient and their doctors to decide whether using ADT with radiation makes sense for them. They can avoid a lot of additional side effects from hormone therapy if their benefit from using combined ADT and radiation is likely to be low.

Were there any unexpected findings from the study?

I was surprised to learn that 1 in 2 men with unfavorable intermediate-risk prostate cancer and 1 in 5 men with high-risk prostate cancer do not obtain clinically significant benefit from using ADT along with radiation. This is in the setting of treatment guidelines that recommend that all men in these risk groups receive combined-modality therapy.

What are the clinical implications of this study?

A substantial number of patients can consider omitting ADT with radiation therapy because they would understand the exact absolute risk reduction of using radiotherapy alone versus radiotherapy plus ADT. This would affect tens of thousands of men in the United States each year and innumerable men worldwide.

What important information did this study provide about choosing a biomarker?

As we saw with our research using Prolaris® when people choose a biomarker to aid in treatment decisions they should use risk models that combine molecular information with known clinical prognosticators. In this way, you can balance problems that biomarkers may have with tumor heterogeneity and sampling errors against subjectivity issues from clinical factors like International Society of Urological Pathology (ISUP) Grade Group. In this case, the combined clinical and genomic expression factors resulted in an incredibly precise and accurate measure of the tumor’s true aggressiveness.

Do you have additional studies planned in this area?

I am looking forward to more research that expands our risk model to see if it can predict who needs short-term versus longer-term ADT with radiation therapy.

Disclosures

Dr. Tward has served on an advisory board or consulted for Bayer; Blue Earth Diagnostics; Janssen Scientific Affairs; Merck; and Myriad Genetics, and received research funding from Bayer.

Reference:

Tward JD, Mantz C, Shore ND, et al. Association of the clinical cell-cycle risk score with metastasis after radiation therapy and identification of men with prostate cancer who can forgo combined androgen deprivation therapy. J Clin Oncol. 2021;39(6, suppl):49. Abstract 195. doi: 10.1200/ JCO.2021.39.6_suppl.195