Carlo Maria I, Giri Veda N, Paller Channing J, Abida Wassim, Alumkal Joshi J, Beer Tomasz M, Beltran Himisha, George Daniel J, Heath Elisabeth I, Higano Celestia S, McKay Rana R, Morgans Alicia K, Patnaik Akash, Ryan Charles J, Schaeffer Edward M, Stadler Walter M, Taplin Mary-Ellen, Kauff Noah D, Vinson Jacob, Antonarakis Emmanuel S, Cheng Heather H
Memorial Sloan-Kettering Cancer Center, New York, NY.
Sidney Kimmel Cancer Center at Thomas Jefferson University, Philadelphia, PA.
JCO Precis Oncol. 2018;2018. doi: 10.1200/PO.18.00060. Epub 2018 Aug 16.
Advances in germline genetics, and related therapeutic opportunities, present new opportunities and challenges in prostate cancer. The Prostate Cancer Clinical Trials Consortium Germline Genetics Working Group was established to address genetic testing for men with prostate cancer, especially those with advanced disease undergoing testing for treatment-related objectives and clinical trials.
The Prostate Cancer Clinical Trials Consortium Germline Genetics Working Group met monthly to discuss the current state of genetic testing of men with prostate cancer for therapeutic or clinical trial purposes. We assessed current institutional practices, developed a framework to address unique challenges in this population, and identified areas of future research.
Genetic testing practices in men with prostate cancer vary across institutions; however, there were several areas of agreement. The group recognized the clinical benefits of expanding germline genetic testing, beyond cancer risk assessment, for the goal of treatment selection or clinical trial eligibility determination. Genetic testing for treatment selection should ensure patients receive appropriate pretest education and consent and occur under auspices of a research study whenever feasible. Providers offering genetic testing should be able to interpret results and recommend post-test genetic counseling for patients. When performing tumor (somatic) genomic profiling, providers should discuss the potential for uncovering germline mutations and recommend appropriate genetic counseling. In addition, family members may benefit from cascade testing and early cancer screening and prevention strategies.
As germline genetic testing is incorporated into practice, further development is needed in establishing prompt testing for time-sensitive treatment decisions, integrating cascade testing for family, ensuring equitable access to testing, and elucidating the role of less-characterized germline DNA damage repair genes, individual gene-level biologic consequences, and treatment response prediction in advanced disease.
生殖系遗传学的进展以及相关治疗机会给前列腺癌带来了新的机遇和挑战。前列腺癌临床试验联盟生殖系遗传学工作组的成立是为了解决前列腺癌男性患者的基因检测问题，尤其是那些患有晚期疾病且为治疗相关目标和临床试验而接受检测的患者。
前列腺癌临床试验联盟生殖系遗传学工作组每月开会讨论前列腺癌男性患者出于治疗或临床试验目的进行基因检测的现状。我们评估了当前各机构的做法，制定了一个框架以应对该人群面临的独特挑战，并确定了未来的研究领域。
前列腺癌男性患者的基因检测做法在各机构之间存在差异；然而，也有几个达成共识的领域。该小组认识到，除了癌症风险评估外，为了选择治疗方案或确定临床试验资格而扩大生殖系基因检测具有临床益处。为选择治疗方案进行的基因检测应确保患者接受适当的检测前教育并获得同意，并且只要可行，应在研究项目的主持下进行。提供基因检测的医疗服务提供者应能够解读检测结果，并为患者推荐检测后的遗传咨询。在进行肿瘤（体细胞）基因组分析时，医疗服务提供者应讨论发现生殖系突变的可能性，并推荐适当的遗传咨询。此外，家庭成员可能会从级联检测以及早期癌症筛查和预防策略中受益。
随着生殖系基因检测被纳入临床实践，在为时间敏感的治疗决策建立快速检测、整合针对家庭成员的级联检测、确保公平获得检测以及阐明特征较少的生殖系DNA损伤修复基因的作用、个体基因水平的生物学后果以及晚期疾病治疗反应预测等方面，还需要进一步发展。
