前列腺癌种系突变检测的实施：2019年费城前列腺癌共识大会

Implementation of Germline Testing for Prostate Cancer: Philadelphia Prostate Cancer Consensus Conference 2019

前列腺癌种系突变检测的实施：2019年费城前列腺癌共识大会

Germline testing (GT) is a central feature of prostate cancer (PCA) treatment, management, and hereditary cancer assessment. Critical needs include optimized multigene testing strategies that incorporate evolving genetic data, consistency in GT indications and management, and alternate genetic evaluation models that address the rising demand for genetic services.

种系突变检测（GT）在前列腺癌（PCA）的治疗、管理和遗传性癌症评估方面起着重要的作用。关键需求包括：优化可包含最新遗传学数据的多基因检测策略，GT适应症和管理具有一致性，以及开发其他遗传评估模式，以满足对遗传服务不断增长的需求。

A multidisciplinary consensus conference that included experts, stakeholders, and national organization leaders was convened in response to current practice challenges and to develop a genetic implementation framework. Evidence review informed questions using the modified Delphi model. The final framework included criteria with strong (> 75%) agreement (Recommend) or moderate (50% to 74%) agreement (Consider).

2019年，众多专家、利益相关者和国家组织领导人汇聚费城，召开了多学科共识会议，该会议旨在应对目前的实践挑战以及制定一个遗传学检测的实施框架。采用改良版德尔菲模型，回顾各个证据，得出相关问题。最终框架包括高度一致（> 75%）（Recommend推荐）或中度一致（50%-74%）（Consider考虑）的标准。

Large germline panels and somatic testing were recommended for metastatic PCA. Reflex testing-initial testing of priority genes followed by expanded testing-was suggested for multiple scenarios. Metastatic disease or family history suggestive of hereditary PCA was recommended for GT. Additional family history and pathologic criteria garnered moderate consensus.

对于转移性PCA患者，建议进行综合性种系突变检测组套和体细胞突变检测。建议在多种情况下采用reflex检测，该检测指先对优先基因进行初始检测，然后进行广泛的基因检测。建议GT用于转移性前列腺癌患者或家族病史提示存在遗传性PCA的患者。其他家族病史和病理学标准的共识程度为中度。

Priority genes to test for metastatic disease treatment included BRCA2, BRCA1, and mismatch repair genes, with broader testing, such as ATM, for clinical trial eligibility. BRCA2 was recommended for active surveillance discussions. Screening starting at age 40 years or 10 years before the youngest PCA diagnosis in a family was recommended for BRCA2 carriers, with consideration in HOXB13, BRCA1, ATM, and mismatch repair carriers. Collaborative (point-of-care) evaluation models between health care and genetic providers was endorsed to address the genetic counseling shortage. The genetic evaluation framework included optimal pretest informed consent, post-test discussion, cascade testing, and technology-based approaches.

对于转移性前列腺癌的治疗，优先检测的基因包括BRCA2、BRCA1和错配修复基因，联合更广泛的基因检测，如ATM基因，可用于评估患者是否符合临床试验的参与资格。对于主动监测的讨论，建议检测BRCA2。对于“在40岁或家族中PCA确诊最小年龄的前10年开始接受筛查”的建议，如果是BRCA2突变携带者，则为强烈推荐，如果是HOXB13、BRCA1、ATM和错配修复基因突变的携带者，则为中等推荐。医疗护理和遗传学服务提供者之间的合作（即时检测）评估模式得到了认可，这种模式可以解决遗传咨询短缺的问题。遗传学评估框架包括最佳检测前知情同意、检测后讨论、级联检测和基于技术的方法。

This multidisciplinary, consensus-driven PCA genetic implementation framework provides novel guidance to clinicians and patients tailored to the precision era. Multiple research, education, and policy needs remain of importance.

这个多学科、共识驱动的PCA遗传学检测实施框架为临床医生和患者提供了针对精准医疗的新型指导。多项研究、教育和政策需求仍然具有重要意义。

Reference:

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