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  • Title: Clinical Implications of Germline Testing in Newly Diagnosed Prostate Cancer.
    Author: Loeb S, Giri VN.
    Journal: Eur Urol Oncol; 2021 Feb; 4(1):1-9. PubMed ID: 33390340.
    Abstract:
    CONTEXT: Germline testing (GT) is increasingly impacting prostate cancer (PCa) management and screening, with direct effects in urology, medical oncology, and radiation oncology. The majority of testing indications and recommendations center on men with metastatic disease, although guidelines now encompass newly diagnosed, early-stage PCa and entail assessment of personal history, pathologic features, and family history to determine eligibility for testing. OBJECTIVE: To describe current guidelines on GT for men with PCa and the impact on management. An additional objective was to review the literature on current uptake of GT across practice settings. EVIDENCE ACQUISITION: A nonsystematic review was performed of current guidelines on GT in PCa from professional societies and consensus conferences, detailing supporting evidence for these recommendations. This was supplemented by a literature review of uptake of GT and precision medicine in practice. EVIDENCE SYNTHESIS: Multiple guidelines and consensus panels recommend GT for men with metastatic PCa. Guidelines endorse BRCA2 testing in metastatic PCa because of strong evidence for PCa risk, aggressiveness, and PARP inhibitor candidacy. Testing of additional DNA repair genes in metastatic disease is also endorsed across guidelines. Immunotherapy with pembrolizumab is an option in some guidelines for men with DNA mismatch repair deficiency. In localized disease, GT is recommended on the basis of histologic features and family history; criteria vary between guidelines. GT for localized disease informs hereditary cancer risk and will probably impact future PCa management. Practice gaps exist regarding utilization of GT. CONCLUSIONS: Germline evaluation is increasingly important in the management of men with metastatic PCa and may also affect the prognosis for men with localized disease. The presence of germline mutations has important hereditary cancer implications for men and their families. Uptake of germline evaluation may be underutilized in some practice settings, so strategies for optimization are required. PATIENT SUMMARY: Patients with prostate cancer should talk to their doctor about the pros and cons of genetic testing, with attention to family history and cancer features. Genetic testing can have important implications for treatment, cancer screening, and family cancer risk.
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