Sociedad de Oncología y Hematología del Cesar, Valledupar, Colombia.
Laboratorio de Diagnóstico Genómico, Instituto Nacional de Medicina Genómica, Ciudad de Mexico, Mexico.
JCO Precis Oncol. 2024 May;8:e2300628. doi: 10.1200/PO.23.00628.
The prevalence of homologous recombination repair gene mutations (HRRm) in patients with metastatic castration-resistant prostate cancer (mCRPC) in Latin America and the Caribbean (LAC) is unknown. Prevalence of homologous Recombination repair (HRR) gene mutatiOns in patientS with metastatic castration resistant ProstatE Cancer in LaTin America (PROSPECT) aimed to determine this prevalence and to describe the demographic and clinical characteristics of the participants.
This was a prospective, cross-sectional, multicenter study across 11 cancer centers in seven LAC countries. After informed consent, all eligible participants underwent genomic testing by provided blood samples for germline HRR testing; they also provided PC tissue blocks if available for somatic HRR testing.
Between April 2021 and April 2022, 387 patients (median age, 70 years [49-89], 94.3% Eastern Cooperative Oncology Group 0-1) with mCRPC were enrolled in the study. Almost 40% of them had a family history of cancer, and the overall time from their initial PC and mCRPC diagnosis was 3 years and 1 year, respectively. The overall prevalence of germline HRRm was 4.2%. The mutations detected included the genes (n = 4, 1%), (n = 3, 0.8%), (n = 3, 0.8%), (n = 2, 0.5%), RAD51B (n = 2, 0.5%), BRCA1 (n = 1, 0.3%), and MRE11 (n = 1, 0.3%). The prevalence of somatic HRRm could not be assessed because of high HRR testing failure rates (79%, 199/251) associated with insufficient DNA, absence of tumor cells, and poor-quality DNA.
Despite the study's limitations, to our knowledge, PROSPECT was the first attempt to describe the prevalence of HRRm in patients with PC from LAC. Notably, the germline HRRm prevalence in this study was inferior to that observed in North American and European populations. The somatic HRR testing barriers identified are being addressed by several projects to improve access to HRR testing and biomarker-based therapies in LAC.
在拉丁美洲和加勒比地区（LAC）的转移性去势抵抗性前列腺癌（mCRPC）患者中，同源重组修复基因突变（HRRm）的流行情况尚不清楚。拉丁美洲转移性去势抵抗性前列腺癌患者同源重组修复（HRR）基因突变的患病率（PROSPECT）旨在确定这种流行情况，并描述参与者的人口统计学和临床特征。
这是一项在 LAC 七个国家的 11 个癌症中心进行的前瞻性、横断面、多中心研究。在获得知情同意后，所有符合条件的参与者都通过提供的血液样本进行了种系 HRR 检测；如果有前列腺癌组织块，他们也提供了这些组织块进行体细胞 HRR 检测。
在 2021 年 4 月至 2022 年 4 月期间，该研究共纳入了 387 例 mCRPC 患者（中位年龄 70 岁[49-89]，94.3%为东部肿瘤协作组 0-1 级）。其中近 40%的患者有癌症家族史，从初始前列腺癌和 mCRPC 诊断到目前为止的时间分别为 3 年和 1 年。种系 HRRm 的总体患病率为 4.2%。检测到的突变包括基因（n = 4，1%）、（n = 3，0.8%）、（n = 3，0.8%）、（n = 2，0.5%）、RAD51B（n = 2，0.5%）、BRCA1（n = 1，0.3%）和 MRE11（n = 1，0.3%）。由于与 HRR 检测失败率（79%，199/251）相关的高 DNA 含量不足、缺乏肿瘤细胞和 DNA 质量差等因素，无法评估体细胞 HRRm 的患病率。
尽管本研究存在一定的局限性，但据我们所知，PROSPECT 是首次尝试描述来自 LAC 的 PC 患者 HRRm 的流行情况。值得注意的是，与北美和欧洲人群相比，本研究中的种系 HRRm 患病率较低。正在通过几个项目来解决确定的体细胞 HRR 检测障碍，以改善 LAC 地区 HRR 检测和基于生物标志物的治疗方法的可及性。
