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    • Repeat Next-Generation Sequencing Testing on Progression in Men with Metastatic Prostate Cancer Can Identify New Actionable Alterations

    JCO PRECISION ONCOLOGY（2024）

    Duke Univ | Univ Michigan | Univ Calif San Diego | Henry Ford Hlth Syst | Tulane Univ | Med Coll Wisconsin | Univ Washington | Emory Univ | Univ Colorado | Oregon Hlth & Sci Univ | City Hope Comprehens Canc Ctr | Univ Calif San Francisco | Holden Comprehens Canc Ctr | Wayne State Univ | Miami Canc Inst

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    Abstract
    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 v 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 BRCA2 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.
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    Metastatic Prostate Cancer,DNA Mismatch Repair,DNA Repair,Prostate Cancer
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    【要点】：本研究评估了美国晚期前列腺癌患者中下一代测序（NGS）测试的使用模式，发现重复NGS测试能够识别新的可操作变异，有助于指导治疗方案的选择。
    

    【方法】：通过回顾性分析前列腺癌精准医疗多机构合作项目数据库中的临床基因组数据，包括15个机构的1,597名患者。
    

    【实验】：研究了9%的患者进行了重复NGS测试（两次或以上，间隔超过60天），其中82.1%的第二轮及以后的测试使用了循环肿瘤DNA（ctDNA）检测，76.1%的样本来自转移性去势抵抗性前列腺癌。在第二轮NGS测试中，11.1%发现了新的可操作数据，其中3.5%检测到了新的BRCA2变异或高度微卫星不稳定性（MSI-high）。在获得可操作结果的第二轮NGS测试后，有31.3%的患者接受了靶向治疗（PARP抑制剂或免疫疗法）。