The Journal of Clinical Oncology recently published an article stating that more detailed assessments of family history of cancer — including prostate, breast, ovarian, colorectal and pancreatic cancers, as well as melanoma — and stage of disease should be used to determine the need for genetic counseling and testing for inherited prostate cancer risk.
“Approximately 5% to 15% of prostate cancer has an inherited predisposition from cancer risk genes, and this percentage may be as high as 20% in metastatic prostate cancer,” Veda N. Giri, MD, associate professor and director of clinical cancer genetics at Sidney Kimmel Cancer Center at Thomas Jefferson University, stated in the report. “However, genetic testing for men with prostate cancer has lagged behind testing for other cancers, with current National Comprehensive Cancer Network guidelines primarily focused on BRCA testing for men with prostate cancer.”
Nearly 33,000 men died from Prostate cancer deaths in 2019, and there is increasing evidence the disease has a substantial inherited predisposition, with higher risks conferred by BRCA2, BRCA1 and HOXB13. Further, according to the study, BRCA2 mutations have been associated with poor prostate cancer-specific outcomes, and emerging evidence links prostate cancer and DNA repair gene mutations.
In 2017, the Philadelphia Prostate Cancer Consensus convened to discuss the gap in genetic testing guidelines for men with prostate cancer and to develop a framework across the spectrum of evaluation focused on the following key questions:
Which men should be considered for genetic counseling and genetic testing?
Which genes should be tested based on clinical and/or familial scenarios?
How should genetic test results inform prostate cancer screening?
Should genetic test results inform management of early-stage/localized; advanced/high-risk; or metastatic, castration-resistant prostate cancer?
More than 70 panelists showed strong consensus to test BRCA1 and BRCA2 for suspected hereditary breast and ovarian cancer, HOXB13 for suspected hereditary prostate cancer, and DNA mismatch repair genes for suspected Lynch syndrome.
The report included the reaction of the panel members, including their recommendations around factoring BRCA2 mutations into prostate cancer screening discussions. BRCA2 achieved moderate consensus for factoring into early-stage management discussion, with stronger consensus in the high-risk/advanced setting.
“Urologists are often on the frontlines of diagnosis and treatment of prostate cancer,” Giri said in the report. “These consensus recommendations point to the need to obtain family history information from men with prostate cancer, which is important in the urology setting to identify men with a potential genetic risk for prostate cancer to consider for genetic evaluation.”
The panel moderately agreed to test all men with metastatic castration-resistant prostate cancer, regardless of family history. The agreement was stronger to test BRCA1 and BRCA2 and moderate to test ATM to inform prognosis and targeted therapy among men with metastatic castration-resistant prostate cancer who chose to undergo genetic testing.
Reference:
Family History, Disease Stage Key In Determining Need for Inherited Prostate Cancer Genetic Testing.
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