A recently published statement provides an evidence-based, consensus-driven framework on the role of genetic testing for determining prostate cancer risk, screening, and management.
A recently released statement from the Philadelphia Prostate Cancer Consensus Conference 2017 addresses the need for comprehensive expert guidance on genetic testing for inherited prostate cancer.
Published online ahead of print in the Journal of Clinical Oncology (Dec. 13, 2017), the paper provides an evidence-based, consensus-driven framework on the role of genetic testing for determining prostate cancer risk, screening, and management.
“Over the last few years, knowledge has increased regarding genes responsible for inherited prostate cancer as well as the capability to do genetic testing, but there is limited guidance on genetic evaluation for men with prostate cancer,” said Veda N. Giri, MD, of Sidney Kimmel Cancer Center (SKCC), Thomas Jefferson University, Philadelphia.
“This consensus conference generated a centralized guideline statement on genetic testing and counseling that is specific for men with prostate cancer. It represents an important first step in pulling together the evidence and expertise in this field, and we expect that it will be expanded and modified over time based on evolving research.”
“The field of genetic testing for prostate cancer is moving ahead rapidly,” said Leonard G. Gomella, MD, of Thomas Jefferson University.
“Urologists are usually the first providers to diagnose and counsel men with prostate cancer. Understanding what is known and what are the limitations of prostate cancer genetic testing is essential.”
The conference was hosted by the SKCC. Karen E. Knudsen, PhD, director, SKCC, served as co-chair of the panel along with Dr. Giri and Dr. Gomella. The panel included 68 additional members representing an international group of experts in medical oncology, radiation oncology, urology, clinical cancer genetics, genetic counseling, population science, research, bioethics, advocacy, and health policy.
There was strong consensus that men with prostate cancer should undergo genetic counseling and genetic testing if they are from families meeting established testing or syndromic criteria for hereditary breast and ovarian cancer (HBOC), hereditary prostate cancer, or Lynch syndrome or if they have two or more close blood relatives on the same side of the family with cancers fitting any of the above cancer syndromes. The recommended tests were for BRCA1/2 in men meeting criteria for HBOC, HOXB13 in men meeting criteria for hereditary prostate cancer, and DNA mismatch repair genes for men meeting criteria for Lynch syndrome.
“An important take-home point for urologists is that in obtaining a family history in their patients, they should be eliciting information not only about prostate cancer but also about breast, ovarian, colorectal, uterine, and pancreatic cancers in both male and female relatives on their maternal and paternal sides,” said Dr. Giri.
She added, “Hopefully, there will be tools developed that will facilitate incorporating this task routinely in a busy clinical practice.”
If men with metastatic castrate-resistant prostate cancer (mCRPC) consider genetic testing, there was high level of consensus to test for mutations in BRCA1/2, and potentially ATM. There was a high level of agreement that men with prostate tumor sequencing showing mutations in specific hereditary cancer genes should have confirmatory germline genetic testing for prostate cancer predisposition.
Recommendations on how genetic test results may inform prostate cancer screening focused on genes with higher level of risk for prostate cancer, such as BRCA2 and HOXB13, with moderate agreement to begin baseline PSA-based screening at age 40 or 10 years prior to the youngest prostate cancer diagnosis in a family, Dr. Giri said.
The panel also addressed the question of how genetic test results may be integrated into prostate cancer management. There was a high level of consensus for factoring in BRCA2 mutation status into management discussions of high-risk/advanced prostate cancer and a moderate level of consensus for incorporating ATM mutation status. There was a high level of consensus for factoring in BRCA1 and BRCA2 mutation status into discussions of treatment for mCRPC and a moderate level of consensus for considering ATM mutation status for such men.
The panel identified a need for more data to determine whether BRCA2 or ATM mutations should be factored into decision–making for management of early-stage/localized prostate cancer. Genetic testing in African American males, cost-effectiveness and quality of life impact of genetic testing for prostate cancer, and the genetics of aggressive prostate cancer were also cited as topics in need of more study.
Now that there is more specific guidance on genetic testing for prostate cancer, Dr. Giri said it is important for urologists to recognize that patients must have an understanding of the implications of genetic testing so they can make an informed decision about undergoing genetic evaluation. She encouraged clinicians to establish a close working relationship with a cancer genetics program.
“The time is ripe for enhanced collaboration between urologists, cancer genetics, and translational research for greater impact on clinical decision-making for men with prostate cancer and their families,” Dr. Giri said.
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