Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA.
Department of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA.
J Clin Oncol. 2020 Aug 20;38(24):2798-2811. doi: 10.1200/JCO.20.00046. Epub 2020 Jun 9.
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 and mismatch repair genes, with broader testing, such as , for clinical trial eligibility. 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 carriers, with consideration in , 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.
种系测试(GT)是前列腺癌(PCA)治疗、管理和遗传性癌症评估的核心特征。关键需求包括优化多基因测试策略,纳入不断发展的遗传数据、GT 指征和管理的一致性,以及解决遗传服务需求增长的替代遗传评估模型。
为应对当前实践挑战,开发遗传实施框架,召集了一个包括专家、利益攸关方和国家组织领导人的多学科共识会议。证据审查使用改良 Delphi 模型为问题提供信息。最终框架包括具有强烈共识(推荐)或中度共识(考虑)的标准(>75%)。
大的种系面板和体细胞测试被推荐用于转移性 PCA。建议在多种情况下进行反射测试——首先对优先基因进行初始测试,然后进行扩展测试。建议对转移性疾病或具有遗传性 PCA 家族史的患者进行 GT。其他家族史和病理标准获得中度共识。用于转移性疾病治疗的优先基因测试包括 和错配修复基因,为临床试验资格进行更广泛的测试,如 。建议在主动监测讨论中进行 。建议 40 岁或家族中最早的 PCA 诊断前 10 年开始对 携带者进行筛查,对 携带者和错配修复基因携带者进行考虑。支持医疗保健和遗传提供者之间的协作(床边)评估模型,以解决遗传咨询短缺问题。遗传评估框架包括优化的术前知情同意、术后讨论、级联测试和基于技术的方法。
这个多学科、共识驱动的 PCA 遗传实施框架为精准医学时代的临床医生和患者提供了新颖的指导。仍有多个研究、教育和政策需求至关重要。