Department of Urology and Population Health, New York University and Manhattan Veterans Affairs, New York, NY, USA.
Cancer Risk Assessment and Clinical Cancer Genetics, Departments of Medical Oncology, Cancer Biology, and Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
Eur Urol Oncol. 2021 Feb;4(1):1-9. doi: 10.1016/j.euo.2020.11.011. Epub 2020 Dec 31.
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.
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.
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.
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.
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.
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.
种系检测（GT）越来越多地影响前列腺癌（PCa）的管理和筛查，对泌尿科、肿瘤内科和放射肿瘤学有直接影响。大多数检测适应证和建议都集中在转移性疾病的男性，尽管指南现在涵盖了新诊断的早期 PCa，并需要评估个人病史、病理特征和家族史，以确定检测的资格。
描述当前针对 PCa 男性的 GT 指南及其对管理的影响。另一个目的是审查当前实践环境中 GT 应用的文献。
对来自专业协会和共识会议的 PCa GT 现行指南进行了非系统性综述，详细介绍了这些建议的支持证据。这一综述通过对 GT 和精准医学在实践中的应用的文献综述进行了补充。
多项指南和共识小组建议对转移性 PCa 男性进行 GT。指南支持 BRCA2 检测转移性 PCa，因为有强有力的证据表明 PCa 风险、侵袭性和 PARP 抑制剂候选。其他 DNA 修复基因在转移性疾病中的检测也得到了指南的认可。在某些指南中，免疫疗法用 pembrolizumab 是 DNA 错配修复缺陷男性的一个选择。在局限性疾病中，GT 是基于组织学特征和家族史推荐的；指南之间的标准有所不同。局限性疾病的 GT 可以提供遗传性癌症风险信息，并可能影响未来的 PCa 管理。在 GT 的应用方面存在实践差距。
在转移性 PCa 男性的管理中，种系评估越来越重要，也可能影响局限性疾病男性的预后。种系突变的存在对男性及其家属具有重要的遗传性癌症意义。在某些实践环境中，种系评估的应用可能不足，因此需要制定优化策略。
前列腺癌患者应与医生讨论基因检测的利弊，重点关注家族史和癌症特征。基因检测对治疗、癌症筛查和家族癌症风险具有重要意义。
