Genomic testing can identify African American prostate cancer patients with high-risk disease

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“Genomic test can identify African-American prostate cancer patients with high-risk disease”

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African American men tend to be diagnosed with prostate cancer more frequently and have higher mortality rates than men of other races and ethnicities. Despite this large disparity in cancer, few prospective studies focused on maximizing the recruitment of African American men have been conducted to address this problem. It is important to identify those men most at risk of poor outcomes to improve treatment management and overall survival.

The Moffitt Cancer Center conducted the first prospective study to investigate genetic biomarkers associated with aggressive disease in African American men with prostate cancer.

Prostate cancer is the most common type of cancer among men in the United States, and approximately 268,490 new cases are expected in 2022. Many men with prostate cancer have good outcomes during treatment and can live a long, cancer-free life. However, some men, including African Americans, have more aggressive disease and worse outcomes.

Doctors usually determine how aggressive a tumor is based on examining tissue samples for cancerous cells. Tissue samples are graded on a scale according to their appearance with the grade 1 group (Gleason score of 6 or less) being non-aggressive until the grade 5 group (Gleason score of 10) being the most aggressive. Additional tests, such as bone scans, MRI and PET scans, are also done to determine if the cancer has spread. However, these examinations and tests are not ideal for identifying aggressive disease because they depend on tumor cell traits and clinical factors, not on differences in tumor genotypes associated with worse outcomes.

Recently, scientists developed a genomic biomarker test called the Decipher score that assesses the expression patterns of 22 genes associated with an increased risk of metastasis. Patients with low-risk genomic disease can be treated with less intensive therapy to reduce unwanted side effects, while patients with higher genomic risk with poorer outcomes can be treated with more intensive therapy to improve overall survival.

The Decipher score was developed with a group of patients that was predominantly white, although additional retrospective studies analyzing historical data found that the Decipher score was able to identify genetic risk among African American men with similar predictive performance. While these retrospective studies are promising, ideal prospective studies that track patient outcomes over time are more plausible.

A team of Moffett researchers led by Kosj Yamoah, MD, Ph.D. , chair of the division of radiation oncology at Moffitt, evaluated whether the Decipher score would be an appropriate test for use in African American men in a prospective study. They partnered with two Tampa-area veterans hospitals – James A. Haley Veterans Affairs and Bay Pines Healthcare VA System – Patient Enrollment, which included 113 African-American men and 113 non-African-American men with low or moderate clinical risk for prostate. Cancer based on clinical features. They discovered that a higher percentage of African American men had higher decoding scores than non-African American men. Furthermore, men who self-identified as African-American were twice as likely to be reclassified as high-risk disease based on scores from the Decipher score than men who self-identified as non-African-American. The researchers also conducted a study of DNA ancestry and confirmed that a subgroup of African-American men were five times more likely to be reclassified based on decoding results than non-African American men.

This research confirms that the use of clinical data alone is not sufficient to identify a subset of patients at greater risk of poor outcomes. These approaches are likely to lose many patients with more aggressive disease and may lead to ineffective therapeutic approaches.

“This study demonstrates the power of using genomic approaches, such as the Decipher scale, to categorize risk in African American men and improve patient outcomes,” Yamoah said. “Our results support the integration of personalized biomarkers with traditional clinical risk classifiers, particularly for African American men, to improve timely detection of genomic aggressive prostate cancer and guide appropriate treatment recommendations.”

Reference: Awasthi S, Grass GD, Torres-Roca J, et al. Genetic testing in localized prostate cancer can identify subgroups of African Americans with aggressive disease. JNCI. 2022: djac162. two: 10.1093/jnci/djac162

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