Image: Genetic testing for detecting high-risk prostate cancer (Photo courtesy of Dr. David Samadi/Oncotype).
To date, there have been few recommendations to guide physicians about when to offer men genetic consultation for prostate cancer risk. A subset of prostate cancers, about 10%-15% of all prostate cancer are inherited and that at least some of the genes that confer the inherited risk are known and testable.
Prostate cancer (PCA) is the third leading cause of cancer-related death in USA men, accounting for 26,730 deaths in 2017. Clinical practice including referrals, genetic counseling, genetic testing, and genetically informed management needs to encompass medical advances and increasingly available commercial genetic tests.
An international and inter-specialty panel of 71 experts convened at the Thomas Jefferson University (Philadelphia, PA, USA) and have developed a comprehensive set of recommendations to guide physicians about when to offer men genetic consultation for prostate cancer risk and this will help physicians and stakeholders make sense of a rapidly evolving field of practice. The goal of the consensus statement was to provide a comprehensive and balanced clinical approach to genetic referrals and testing relevant to clinical cancer genetics specialists, genetic counselors, urologists, oncologists, and primary care providers to provide men with an opportunity to make an informed decision regarding genetic testing, screening, and personalized treatment.
The group's key findings and recommendations included that while current commercially available genetic tests specifically for inherited prostate cancer risk can cover anywhere from 10-14 genes (and even larger cancer gene panels are available), clinical actionability for prostate cancer screening and management are relevant for a subset of these genes. For example, men with prostate cancer with inherited mutations in the breast cancer 2 (BRCA2), breast cancer 1, early onset (BRCA1), and Ataxia Telangiectasia Mutated (ATM) genes may respond to polyadenosine diphosphate-ribose polymerase (PARP) inhibitors, especially if prostate cancer has progressed to metastasis and is resistant to initial treatments.
The following genes should be tested in males with PCA meeting criteria for the corresponding syndrome: HOXB13 (Syndrome: Hereditary pancreatitis [HPC]); BRCA1/BRCA2 (Syndrome: Hereditary breast and ovarian cancer [HBOC]), DNA mismatch repair (MMR) genes. Men with PCA with two or more close blood relatives on the same side of the family with a cancer should get tested. Others who may need testing are men with metastatic, hormone-sensitive PCA to identify germline mutations to inform potential future treatment options and cascade testing in families and men with tumor sequencing showing mutations in cancer-risk genes should be recommended for germline testing, particularly after factoring in additional personal history and specific family history.
Leonard Gomella, MD, a senior author of the study, said, “With a multitude of genetic tests on the market already, the technology provides more information right now, than we can act upon in the clinic. A genetic test can reveal mutations that could impact a son, daughter, sister, brother or other relatives and reveal higher risks of cancer across a family, which is why men need to understand the implications of genetic testing.” The study was published on December 13, 2017, in the Journal of Clinical Oncology.
Thomas Jefferson University