对转移性前列腺癌进展患者进行重复下一代测序检测可识别新的可操作改变。
Repeat Next-Generation Sequencing Testing on Progression in Men With Metastatic Prostate Cancer Can Identify New Actionable Alterations.
机构信息
Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, NC.
Division of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI.
出版信息
JCO Precis Oncol. 2024 Apr;8:e2300567. doi: 10.1200/PO.23.00567.
PURPOSE
There are limited data available on the real-world patterns of molecular testing in men with advanced prostate cancer. We thus sought to evaluate next-generation sequencing (NGS) testing in the United States, focused on single versus serial NGS testing, the different disease states of testing (hormone-sensitive castration-resistant, metastatic vs nonmetastatic), tissue versus plasma circulating tumor DNA (ctDNA) assays, and how often actionable data were found on each NGS test.
METHODS
The Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort clinical-genomic database was used for this retrospective analysis, including 1,597 patients across 15 institutions. Actionable NGS data were defined as including somatic alterations in homologous recombination repair genes, mismatch repair deficiency, microsatellite instability (MSI-high), or a high tumor mutational burden ≥10 mut/MB.
RESULTS
Serial NGS testing (two or more NGS tests with specimens collected more than 60 days apart) was performed in 9% (n = 144) of patients with a median of 182 days in between test results. For the second NGS test and beyond, 82.1% (225 of 274) of tests were from ctDNA assays and 76.1% (217 of 285) were collected in the metastatic castration-resistant setting. New actionable data were found on 11.1% (16 of 144) of second NGS tests, with 3.5% (5 of 144) of tests detecting a new alteration or MSI-high. A targeted therapy (poly (ADP-ribose) polymerase inhibitor or immunotherapy) was given after an actionable result on the second NGS test in 31.3% (5 of 16) of patients.
CONCLUSION
Repeat somatic NGS testing in men with prostate cancer is infrequently performed in practice and can identify new actionable alterations not present with initial testing, suggesting the utility of repeat molecular profiling with tissue or blood of men with metastatic castration-resistant prostate cancer to guide therapy choices.
目的
关于晚期前列腺癌男性的分子检测实际模式，现有数据有限。因此，我们评估了美国的下一代测序（NGS）检测，重点是单次与连续 NGS 检测、检测的不同疾病状态（激素敏感型去势抵抗性、转移性与非转移性）、组织与血浆循环肿瘤 DNA（ctDNA）检测，以及每种 NGS 检测中发现的可采取行动数据的频率。
方法
本回顾性分析使用了前列腺癌精准医学多机构合作努力临床基因组数据库，纳入了 15 个机构的 1597 名患者。可采取行动的 NGS 数据定义为包括同源重组修复基因的体细胞改变、错配修复缺陷、微卫星不稳定性（MSI-high）或高肿瘤突变负荷≥10 mut/MB。
结果
9%（n=144）的患者进行了连续 NGS 检测（两次或更多次 NGS 检测，标本采集间隔超过 60 天），两次检测结果之间的中位间隔为 182 天。对于第二次及以后的 NGS 检测，82.1%（225/274）的检测来自 ctDNA 检测，76.1%（217/285）在转移性去势抵抗性环境中采集。11.1%（16/144）的第二次 NGS 检测发现了新的可采取行动数据，3.5%（5/144）的检测发现了新的改变或 MSI-high。在第二次 NGS 检测发现可采取行动的结果后，31.3%（5/16）的患者接受了靶向治疗（聚（ADP-核糖）聚合酶抑制剂或免疫疗法）。
结论
在实践中，男性前列腺癌的重复体细胞 NGS 检测很少进行，但可以识别初始检测中未发现的新的可采取行动的改变，这表明对转移性去势抵抗性前列腺癌男性的组织或血液进行重复分子谱分析以指导治疗选择具有实用性。
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