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Recent Guidelines in Germline testing for Prostate Cancer
Overview
USA: With the increasing role of germline testing in Prostate Cancer (PCa) care, there is a need for understanding the nuances of genetic predisposition, current guidelines and considerations regarding germline testing, precision therapy and genetically based screening, and the practical aspects of genetic counseling and testing revolving Pca.
This pushed Dr. Thenappan Chandrasekar, MD, and his team from Philadelphia to analyze and summarise the various genetic testing on the ground, the findings were further published in the Journal of Urologic Clinics of North America, Volume 48 on August 2021.
The major bits of the article
• Early genome-wide association studies in 2010 recognized more than 100 potential loci, which collectively, are thought to account for 33% of FPC risk. This is an active research field, with polygenic risk scores becoming available for testing.
• Men with germline mutations in DNA damage repair genes, such as BRCA2, BRCA1, and ATM, appeared to be susceptible for PARP inhibitors in the setting of advanced PCa.
• Following prior treatment with enzalutamide or abiraterone acetate and/or taxane-based chemotherapy, the National Comprehensive Cancer Network (NCCN) now recommends that clinicians offer a PARP inhibitor to patients with deleterious or suspected deleterious germline or somatic homologous recombination repair gene mutated mCRPC.
• The recommended guidelines in the current Germline testing includes Men with high-risk or very high-risk localized PCa, men with metastatic PCa, men with intraductal or cribriform histology, men with Ashkenazi Jewish ancestry, men with a family history of high-risk germline mutations, and known germline variants (BRCA1/2, Lynch syndrome, ATM, PALB2, CHEK2), and men with a family history of high-risk germline mutations and known germline variants (BRCA1/2, Lynch syndrome ATM, PALB2, CHEK2).
• The list goes on with including men with a positive strong history of PCa (first-degree relative with PCa death or diagnosed < age 60) and cancers associated with hereditary breast and ovarian cancer or Lynch syndrome.
• Numerous studies stress the necessity of test result counseling both pretest and post-testing to aid with the delivery of complete genetically and family history–based advice as well as the ambiguity around some test findings.
• The present treatment paradigm relies on a nongenetic provider (clinician) referring an at-risk individual to an in-person GC for pretest counseling, genetic testing, and posttest counseling once a nongenetic provider (clinician) finds them.
• The growing disparity between the number of males with PCa who are referred for germline genetic testing and the availability and accessibility of GC is a major healthcare delivery flaw.
For further insight
Thenappan Chandrasekar, William K. Kelly, Leonard G. Gomella, Overview of Prostate Cancer Genetic Testing, Urologic Clinics of North America, Volume 48, Issue 3, 2021, Pages 279-282, ISSN 0094-0143, ISBN 9780323791670, https://doi.org/10.1016/j.ucl.2021.04.002.