ASCO Perspective
“Current prostate cancer screening recommendations rely on family history as well as race and ethnicity, factors which often don’t fully capture a person’s risk of developing or dying from prostate cancer. This new study suggests that an extensive genetic risk score could be an effective tool to guide screening decisions by identifying people at high or low risk of developing metastatic prostate cancer. Importantly, this tool been validated in a diverse population,” said Robert Dreicer, MD, MS, MACP, FASCO, ASCO Expert in genitourinary cancers.

ALEXANDRIA, Va. – A scoring algorithm that incorporated 290 genetic variants for prostate cancer (PHS290) accurately identified people with high or low lifetime risks of developing metastatic prostate cancer or dying from the disease. Based on the risk scores, people with an African ancestry had the highest risk of developing metastatic prostate cancer and dying of the disease. The study will be presented at the 2022 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, taking place February 17-19, 2022, in San Francisco, California.

Study at a Glance

Current screening for prostate cancer often includes a prostate-specific antigen (PSA) test, but there is uncertainty about the precision of the test and its utility in accurately predicting risk of developing aggressive forms of the disease. Researchers have been trying to develop more accurate tests for decades as prostate cancer remains a deadly disease. An estimated 34,500 men will die of the disease in the United States in 2022; in recent years, the risk of dying from prostate cancer, which had been steadily declining, has slowed, decreasing by less than one percent per year.¹

“While most prior genetic studies have focused on men of European ancestry, our scoring algorithm is a measure of risk of dying of prostate cancer in a diverse population of military veterans,” said lead study author Meghana Pagadala, VA Health Care System, La Jolla, California, and an MD/PhD candidate at the University of California, San Diego. “Even accounting for family history and ancestry, the scoring algorithm provided powerful additional information about a man’s risk of death due to prostate cancer.”

Because prostate cancer is one of the most heritable cancers, variations in a person’s genetic makeup may contribute greatly to their risk for disease. The algorithm incorporates 290 previously identified gene variants associated with prostate cancer risk. Presence or absence of each variant and the patients’ ages were applied to the algorithm to generate an optimal model for association with age at prostate cancer diagnosis.

About the Study

Since 2011, the Million Veterans Study has enrolled over 650,000 people receiving medical care at 63 facilities nationwide that are part of the Veterans Administration Health Care System. About 600,000 of the enrollees were male and researchers were able to obtain clinical information for nearly 97% of those men. About 425,000 had a European ancestry and about 105,000 had an African ancestry, while the remaining had either Asian or Hispanic heritages. The men in the study were a median age of 69 and all consented to donate blood for genotyping.

“Compared to other tests of risk, the scoring algorithm uses nearly 300 variants linked to inherited genetic information, whereas some currently available commercial tests rely on expression of just a dozen or so cancer-related genes and a handful of reference genes,” said Pagadala. “One advantage to heritable genetic information is that is does not change through a person’s lifetime, whereas tumor gene expressions can be highly variable and are only available once a man has already developed the disease. This algorithm was developed to predict risk of prostate cancer at different ages.”

Key Findings

Risk of death was 4.41 times higher for men in the top 20% of scores as determined by the PHS290 algorithm compared to those whose genetic risk score was in the lowest 20%. The risk for developing prostate cancer or having the disease metastasize was 5.66 times higher and 4.18 times higher for those in the top 20% of risk scores compared to those in the lowest 20%, respectively.

When looking at ancestry, using European ancestry as a reference group, the most pronounced outcomes based on a PHS290 score were in people with an African ancestry, who had a 1.84 times greater risk for developing prostate cancer compared to people of European ancestry. There was a 2.27 times greater risk for prostate cancer metastasis and a 1.97 times greater risk for death based on risk scores in people of African ancestry compared to those of European ancestry. Although the authors reported data on men with Asian ancestry, the number in the analysis was too small to determine a reliable estimate of risk. Risk for people of Hispanic ancestry tracked closely with those of European ancestry. Family history of prostate cancer also conferred a greater risk of developing and dying of prostate cancer.

Next Steps

The scoring algorithm is not yet commercially available.

The researchers hope to identify more ancestry-specific prostate cancer risk variants and better understand how to incorporate ancestry into estimating genetic risk. In addition, they plan to look at the interaction of genetic risk and environmental factors.

This study received funding from the Million Veteran Program MVP022 award # I01 CX001727 to Richard L. Hauger. Hauger was also funded by the VISN-22 VA Center of Excellence for Stress and Mental Health (CESAMH) and National Institute of Aging RO1 grant AG050595 (The VETSA Longitudinal Twin Study of Cognition and Aging VETSA 4). Meghana S. Pagadala was supported by NIH grants 1F30CA247168 and T32CA067754. Tyler Seibert and Roshan Karunamuni were supported by an NIH/NIBIB grant K08EB026503, the Prostate Cancer Foundation, and the University of California grant C21CR2060.

View the full abstract

For your readers:
Prostate Cancer

View the disclosures for the 2022 ASCO Genitourinary Cancers Symposium News Planning Team: https://www.asco.org/sites/new-www.asco.org/files/content-files/about-asco/2022-ASCO-GU-NPT-Disclosures.pdf

ATTRIBUTION TO THE 2022 ASCO GENITOURINARY CANCERS SYMPOSIUM MEETING IS REQUESTED IN ALL COVERAGE.

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[1] Cancer Facts and Figures, 2022: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2022/2022-cancer-facts-and-figures.pdf