Genetic testing is recommended for all men with metastatic prostate cancer (PCa) or who have a family history indicative of hereditary PCa, according to a new consensus guideline.
In addition, the guideline emphasizes the importance of considering family history beyond PCa, such as hereditary breast and ovarian cancer and Lynch syndrome, which have cancer risk implications for men and their families. Further, the guideline strongly recommends BRCA2 be included in all testing scenarios to inform precision therapy in metastatic disease, to inform active surveillance discussions in early-stage disease, and to inform PCa early detection discussions and strategies.
The guideline, which was published in the Journal of Clinical Oncology, was developed by attendees of the 2019 Philadelphia Prostate Cancer Consensus Conference hosted by the Sidney Kimmel Cancer Center at Thomas Jefferson University in Philadelphia. The conference included 97 participants representing the fields of urology, medical oncology, radiation oncology, clinical genetics, genetic counseling, and others.
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“The consensus statement is important because, with the rising volume of men in need of germline testing, there is increasing demand for genetic counseling, and healthcare providers are ordering genetic testing to impact treatment and management,” corresponding author Veda N. Giri, MD, Associate Professor, Medical Oncology, Cancer Biology, and Urology, and Director, Cancer Risk Assessment and Clinical Cancer Genetics at Sidney Kimmel Cancer Center, told Renal & Urology News. “Importantly, there will be an expected rise in germline testing to identify men with metastatic prostate cancer for PARP inhibitor therapy given the recent FDA approvals for rucaparib and olaparib. This consensus conference addressed how to implement responsible germline testing in this era of precision medicine with focus on which men to test, delivery of informed consent for testing, which panels are more suited for various clinical scenarios, and how results impact treatment, management, and families. Thus, we hope the consensus-driven framework for implementation of germline testing will be useful for healthcare providers, genetic counselors, and patients to streamline access to germline testing for prostate cancer.”
For patients with metastatic PCa, the guideline recommends germline testing priority be given to BRCA1/BRCA2 and DNA MMR genes, and that the ATM gene be considered for testing. The guideline also recommends that additional genes be tested based on patients’ personal or family history.
“Broad panel testing may be more applicable in the metastatic setting for identifying therapeutic options and clinical trials eligibility,” Dr Giri said. “Reflex testing may be more suitable for models of collaboration with genetic counseling where healthcare providers may be initiating genetic testing.”
For men with non-metastatic PCa, the guideline recommends that germline testing be considered for men with Ashkenazi Jewish ancestry, advanced disease (T3a or higher), intraductal or ductal pathology, or Grade Group 4 disease (Gleason sum 8) or higher.
Germline testing is recommended for men with 1 brother or father or 2 or more male relatives diagnosed with PCa when they were younger than 60 years, died from PCa, or had metastatic PCa.
The guideline also lists “key premises” for guiding genetic evaluation. “Patients’ psychosocial needs or preferences should dictate the mode of counseling,” reads one premise. In addition, the panel noted that a full family history is important to collect during the genetic evaluation process. The panel also recommends that men should engage in informed decision making for genetic testing and said building collaborations between healthcare and genetics providers is important for optimal genetic evaluation.
“Referral to a genetic counselor is important for men with mutations identified and may be needed for men with variants of uncertain significance, strong family cancer history, patient anxiety, or patient preference,” Dr Giri said. “Furthermore, since genetic testing can have hereditary cancer implications, genetic testing of family members of men with genetic mutations, called cascade testing, should be under the care of a genetic counselor. These are exciting times for genetic testing for men and their families to address cancer risk and treatment.”
Reference
Giri VN, Knudsen KE, Kelly WK, et al. Implementation of germline testing for prostate cancer: Philadelphia Prostate Cancer Consensus Conference 2019 [published online June 9, 2020]. J Clin Oncol. 2020. https://doi.org/10.1200/JCO.20.00046
