An estimated 20% to 30% of men with advanced prostate cancer carry a mutation in DNA damage repair genes, of which half are estimated to be germline. Eligibility criteria for germline genetic testing expanded significantly for Ontario patients in May 2021 and many centers adopted a “mainstream” model, defined as oncologist-initiated genetic testing. We conducted a retrospective chart review to report on the first-year mainstream experience of a large tertiary oncologic center, the Sunnybrook Odette Cancer Centre. All patients who underwent mainstream at the discretion of their treating physician were included. A subset underwent somatic profiling as part of clinical trial screening. Descriptive statistics were used to report baseline clinicopathologic characteristics and treatments received. Between May 1, 2021, and May 30, 2022, 174 patients with prostate cancer underwent mainstream germline genetic testing with a 19-gene panel. Median age was 75 (IQR 68-80), and 82% of patients were diagnosed with either de novo metastatic or high-risk localized prostate adenocarcinoma. Fourteen patients (8%; 95% CI 4%-12%) were found to have a deleterious germline mutation, including pathogenic or likely pathogenic variants in and . Forty-nine patients (28%; 95% CI 21%-35%) were found to have a variant of uncertain significance. Thirty-four patients also had next-generation sequencing (NGS) of their somatic tissue. Among this subset, 8 of 34 (23%) had an alteration in homologous recombination repair (HRR) genes. Of the 14 patients with a germline mutation, none had a prior personal history of malignancy and 6 (43%) did not have any first- or second-degree relatives with history of prostate, pancreatic, breast, or ovarian cancer. We report on the real-world characteristics of prostate cancer patients who underwent mainstream germline genetic testing. Personal history and family history of cancer cannot reliably stratify patients for the presence of pathogenic germline variants.

中文翻译：

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大型三级癌症中心前列腺癌基因检测的主流模型

据估计，20% 至 30% 的晚期前列腺癌男性携带 DNA 损伤修复基因突变，其中一半估计是种系突变。 2021 年 5 月，安大略省患者的种系基因检测资格标准显着扩大，许多中心采用了“主流”模式，定义为肿瘤学家发起的基因检测。我们进行了回顾性图表审查，报告大型三级肿瘤中心 Sunnybrook Odette 癌症中心第一年的主流经验。所有根据治疗医生的判断接受主流治疗的患者都被包括在内。作为临床试验筛选的一部分，对一个子集进行了体细胞分析。使用描述性统计报告基线临床病理特征和接受的治疗。 2021年5月1日至2022年5月30日期间，174名前列腺癌患者接受了19基因组的主流种系基因检测。中位年龄为 75 岁（IQR 68-80），82% 的患者被诊断患有新发转移性或高风险局限性前列腺腺癌。 14 名患者（8%；95% CI 4%-12%）被发现具有有害的种系突变，包括 和 中的致病性或可能致病性变异。 49 名患者（28%；95% CI 21%-35%）被发现具有不确定意义的变异。 34 名患者的体细胞组织还进行了下一代测序 (NGS)。在这个子集中，34 个基因中有 8 个 (23%) 的同源重组修复 (HRR) 基因发生了改变。在 14 名患有种系突变的患者中，没有人有恶性肿瘤病史，6 名 (43%) 的一级或二级亲属没有前列腺癌、胰腺癌、乳腺癌或卵巢癌病史。我们报告接受主流种系基因检测的前列腺癌患者的真实特征。癌症的个人史和家族史不能可靠地对患者是否存在致病性种系变异进行分层。