New Study Questions Guidelines for Genetic Screening for Prostate Cancer

It may be time to re-evaluate and possibly broaden the current genetic screening guidelines for prostate cancer, according to researchers at the University of Utah Health. Their study, published in the June issue of Cancer, showed that men with prostate cancer and at least one additional primary cancer are enriched for harboring a germline deleterious mutation in a cancer-predisposing gene, which may impact cancer prognosis and treatment. However, the majority of these men may not meet current criteria for clinical genetic testing, according to the researchers.

The researchers looked at the prevalence of pathogenic germline variants in cancer-predisposing genes in men with prostate cancer and at least one additional primary cancer. They sequenced germline DNA from 102 men with prostate cancer and at least one additional primary cancer using a multigene panel. The sequencing identified approximately 3,500 variants. Nine protein-truncating deleterious mutations were found across six genes (BRCA2, ATM, MLH1, BRIP1, PALB2, and FGFR3).

“The majority of the men harboring deleterious mutations in a cancer predisposing gene did not meet current guidelines for genetic testing. In addition, by using a panel-testing approach focused on actionable cancer-related genes, we identified a diverse set of germline mutations in these men that centers mostly around the DNA damage repair pathway,” said study investigator Patrick Pilié, MD, a medical oncology fellow at the University of Texas MD Anderson Cancer Center in Houston, Texas.

Dr. Pilié said these mutations are not only risk-stratifying but are also now increasingly predictive of response to targeted therapies, including platinum-based chemotherapy and PARP inhibition.

Study investigator Kathleen Cooney, MD, chair of the Department of Internal Medicine at University of Utah Health, Salt Lake City, said identifying pathogenic germline mutations in men with prostate cancer has important implications for the treatment of an identified carrier’s cancer. In addition, it has implications for risk-stratification, cancer screening, and prevention for entire families.

“Our study highlights an important subgroup of men with prostate cancer and multiple primary malignancies who should be considered for referral to a cancer genetics clinic for genetic testing,” Dr. Cooney told OncoTherapy Network. “Gene panel–based testing focused on actionable cancer-related genes under the direction of a genetic counselor could be particularly suited for this unique population.”

A certified genetic counselor reviewed personal and family histories from each patient to determine whether they would meet clinical genetic testing guidelines. The majority of the men in the study (64%) did not meet current criteria to test for hereditary cancer based on personal and/or family history.

Dr. Cooney said this study of men with multiple primary malignancies should inspire larger studies to confirm these initial findings. “Confirmation of our study results should prompt a re-evaluation and possible broadening of current genetic screening guidelines for prostate cancer,” explained Dr. Cooney.