Background

Homologous recombination repair mutation (HRRm) status may guide risk-stratification and treatment decisions, including polyadenosine diphosphate–ribose polymerase inhibitor use, in advanced prostate cancer. Although HRRm prevalence has been reported in single-institution studies or clinical trials, real-world HRRm prevalence in diverse populations is unknown. We describe HRRm in the clinical setting using two real-world clinicogenomic databases: the Flatiron Health and Foundation Medicine, Inc. Clinico-Genomic Database (CGDB), a national electronic health record-derived database, and the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (GENIE).

Methods

This cross-sectional analysis included 3757 individuals diagnosed with prostate cancer who had next generation sequencing (NGS) as standard of care. The CGDB included men with advanced/metastatic prostate cancer and genetic data included both germline and somatic pathogenic mutations. The GENIE analysis included men with prostate cancer whose received NGS as standard of care, but the data were filtered to include somatic mutations only. Due to key differences among databases, direct comparisons were not possible. Overall prevalence of HRRm was calculated and stratified by demographic and clinical characteristics.

Results

HRRm prevalence (combined germline and somatic) in CGDB (n = 487) was 24.6% (95% CI 20.9–28.7%), with no major differences across demographic and disease characteristic subgroups. HRRm prevalence (somatic) in GENIE (n = 3270) was 11.0% (95% CI 10.0–12.1%), which varied between 9.5% and 18.4% across treatment centers.

Conclusions

Approximately one-quarter of patients with advanced/metastatic prostate cancer in the CGDB had germline and/or somatic HRRm, which is consistent with clinical trials such as the PROfound study that used a similar NGS platform and algorithm to define HRRm. In the GENIE database, HRRm prevalence varied by treatment center or NGS platform. More research is needed to understand real-world HRRm prevalence variations.

中文翻译：

---

晚期前列腺癌中同源重组修复突变的真实患病率：对两个临床基因组数据库的分析

背景

同源重组修复突变（HRRm）状态可以指导晚期前列腺癌的风险分层和治疗决策，包括聚腺苷二磷酸核糖聚合酶抑制剂的使用。尽管在单一机构研究或临床试验中已报告了 HRRm 患病率，但不同人群中真实世界的 HRRm 患病率尚不清楚。我们使用两个真实世界的临床基因组数据库描述临床环境中的 HRRm：Flatiron Health 和 Foundation Medicine, Inc. 临床基因组数据库 (CGDB)、国家电子健康记录衍生数据库和美国癌症研究项目基因组学协会肿瘤证据信息交换（GENIE）。

方法

这项横断面分析包括 3757 名被诊断患有前列腺癌的个体，他们将下一代测序 (NGS) 作为护理标准。CGDB 包括患有晚期/转移性前列腺癌的男性，遗传数据包括种系和体细胞致病突变。GENIE 分析包括接受 NGS 作为护理标准的前列腺癌男性，但数据经过过滤仅包括体细胞突变。由于数据库之间的关键差异，无法进行直接比较。HRRm 的总体患病率根据人口统计和临床特征进行计算和分层。

结果

CGDB ( n = 487)中的 HRRm 患病率（结合种系和体细胞） 为 24.6% (95% CI 20.9–28.7%)，人口统计学和疾病特征亚组之间没有重大差异。GENIE ( n  = 3270) 中的 HRRm 患病率（体细胞）为 11.0% (95% CI 10.0–12.1%)，不同治疗中心的患病率在 9.5% 至 18.4% 之间变化。

结论

CGDB 中大约四分之一的晚期/转移性前列腺癌患者具有种系和/或体细胞 HRRm，这与 PROfound 研究等临床试验一致，该研究使用类似的 NGS 平台和算法来定义 HRRm。在 GENIE 数据库中，HRRm 患病率因治疗中心或 NGS 平台而异。需要更多的研究来了解现实世界中 HRRm 患病率的变化。