胚系测试(GT)是前列腺癌(PCA)治疗的主要特征,管理,和遗传性癌症评估。关键需求包括优化的多基因检测策略,整合不断发展的遗传数据,GT适应症和管理的一致性,和替代遗传评估模型,以解决对遗传服务不断增长的需求。
由专家组成的多学科共识会议,利益相关者,和国家组织领导人召集会议,以应对当前的实践挑战,并制定遗传实施框架。使用改进的德尔菲模型进行证据审查知情问题。最终框架包括具有强(>75%)协议(推荐)或中等(50%至74%)协议(考虑)的标准。
对于转移性PCA,建议进行大型种系面板和体细胞测试。针对多种情况,建议进行反射测试-对优先基因进行初始测试,然后进行扩展测试。建议将提示遗传性PCA的转移性疾病或家族史用于GT。其他家族史和病理标准获得了中度共识。用于转移性疾病治疗的优先基因包括BRCA2、BRCA1和错配修复基因。通过更广泛的测试,比如ATM,临床试验资格。BRCA2被推荐用于主动监测讨论。从40岁或10岁开始筛查,建议对BRCA2携带者进行家庭中最年轻的PCA诊断。在HOXB13,BRCA1,ATM,和失配修复载体。卫生保健和遗传提供者之间的协作(护理点)评估模型得到了认可,以解决遗传咨询短缺的问题。遗传评估框架包括最佳预测试知情同意,测试后讨论,级联测试,和基于技术的方法。
这个多学科,共识驱动的PCA基因实施框架为临床医生和患者提供了适合精确时代的新指导。多项研究,教育,政策需求仍然很重要。
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.
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).
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. 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.
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.