PDF(Pubmed)
Abstract：
BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a noninvasive technique that provides valuable insights into molecular profiles and tumor disease management. This study aimed to evaluate the prognostic significance of circulating tumor DNA (ctDNA) in urothelial carcinoma (UC) through a systematic review and meta-analysis.
METHODS: A comprehensive search was conducted in MEDLINE, EMBASE, and the Cochrane Library from the inception to December 2023. Studies investigating the prognostic value of ctDNA in UC were included. Hazard ratios (HRs) of disease-free survival (DFS) and overall survival (OS) were extracted. Overall meta-analysis and subgroup exploration stratified by metastatic status, ctDNA sampling time, treatment type, and detection method was performed using the R software (version 4.2.2).
RESULTS: A total of 16 studies with 1725 patients were included. Fourteen studies assessed the association between baseline ctDNA status and patient outcomes. Patients with elevated ctDNA levels exhibited significantly worse DFS (HR=6.26; 95% CI: 3.71-10.58, P <0.001) and OS (HR=4.23; 95% CI: 2.72-6.57, P <0.001) regardless of metastatic status, ctDNA sampling time, treatment type, and detection methods. Six studies evaluated the prognostic value of ctDNA dynamics in UC. Patients who showed a decrease or clearance in ctDNA levels during treatment or observation demonstrated more favorable DFS (HR=0.26, 95% CI: 0.17-0.41, P <0.001) and OS (HR=0.21, 95% CI: 0.11-0.38, P <0.001) compared to those who did not. The association remained consistent across the subgroup analysis based on metastatic status and detection methods. In the immune checkpoint inhibitor-treated setting, both lower baseline ctDNA level and ctDNA decrease during the treatment were significantly associated with more favorable oncologic outcomes. Furthermore, specific gene mutations such as FGFR3 identified in ctDNA also demonstrated predictive value in UC patients.
CONCLUSIONS: This meta-analysis demonstrates a strong association of ctDNA status and its dynamic change with survival outcomes in UC, suggesting substantial clinical utility of ctDNA testing in prognosis prediction and decision making in this setting.
METHODS: A comprehensive search was conducted in MEDLINE, EMBASE, and the Cochrane Library from the inception to December 2023. Studies investigating the prognostic value of ctDNA in UC were included. Hazard ratios (HRs) of disease-free survival (DFS) and overall survival (OS) were extracted. Overall meta-analysis and subgroup exploration stratified by metastatic status, ctDNA sampling time, treatment type, and detection method was performed using the R software (version 4.2.2).
RESULTS: A total of 16 studies with 1725 patients were included. Fourteen studies assessed the association between baseline ctDNA status and patient outcomes. Patients with elevated ctDNA levels exhibited significantly worse DFS (HR=6.26; 95% CI: 3.71-10.58, P <0.001) and OS (HR=4.23; 95% CI: 2.72-6.57, P <0.001) regardless of metastatic status, ctDNA sampling time, treatment type, and detection methods. Six studies evaluated the prognostic value of ctDNA dynamics in UC. Patients who showed a decrease or clearance in ctDNA levels during treatment or observation demonstrated more favorable DFS (HR=0.26, 95% CI: 0.17-0.41, P <0.001) and OS (HR=0.21, 95% CI: 0.11-0.38, P <0.001) compared to those who did not. The association remained consistent across the subgroup analysis based on metastatic status and detection methods. In the immune checkpoint inhibitor-treated setting, both lower baseline ctDNA level and ctDNA decrease during the treatment were significantly associated with more favorable oncologic outcomes. Furthermore, specific gene mutations such as FGFR3 identified in ctDNA also demonstrated predictive value in UC patients.
CONCLUSIONS: This meta-analysis demonstrates a strong association of ctDNA status and its dynamic change with survival outcomes in UC, suggesting substantial clinical utility of ctDNA testing in prognosis prediction and decision making in this setting.
摘要：
背景：循环肿瘤DNA（ctDNA）已成为一种非侵入性技术，可为分子谱和肿瘤疾病管理提供有价值的见解。本研究旨在通过系统评价和荟萃分析评估循环肿瘤DNA（ctDNA）在尿路上皮癌（UC）中的预后意义。
方法：在MEDLINE中进行了全面搜索，EMBASE,和Cochrane图书馆从成立到2023年12月。包括研究ctDNA在UC中的预后价值的研究。提取无病生存率（DFS）和总生存率（OS）的危险比（HR）。总体荟萃分析和按转移状态分层的亚组探索，ctDNA采样时间，治疗类型,检测方法使用R软件(4.2.2版).
结果：共纳入16项研究，共1725例患者。14项研究评估了基线ctDNA状态与患者预后之间的关联。无论转移状态如何，ctDNA水平升高的患者的DFS（HR=6.26;95％CI，3.71-10.58，P<0.001）和OS（HR=4.23;95％CI，2.72-6.57，P<0.001）均显着降低。ctDNA采样时间，治疗类型和检测方法。六项研究评估了ctDNA动力学在UC中的预后价值。在治疗或观察期间显示ctDNA水平降低或清除的患者表现出更有利的DFS（HR=0.26，95％CI，0.17-0.41，P<0.001）和OS（HR=0.21，95％CI，0.11-0.38，P<0.001）。基于转移状态和检测方法的亚组分析中的关联保持一致。在免疫检查点抑制剂治疗的环境中，基线ctDNA水平较低和治疗期间ctDNA减少均与更有利的肿瘤学结局显著相关.此外，ctDNA中鉴定的FGFR3等特定基因突变在UC患者中也具有预测价值.
结论：本荟萃分析显示ctDNA状态及其动态变化与UC患者的生存结局密切相关，提示在这种情况下，ctDNA检测在预后预测和决策中具有重要的临床实用性。
方法：在MEDLINE中进行了全面搜索，EMBASE,和Cochrane图书馆从成立到2023年12月。包括研究ctDNA在UC中的预后价值的研究。提取无病生存率（DFS）和总生存率（OS）的危险比（HR）。总体荟萃分析和按转移状态分层的亚组探索，ctDNA采样时间，治疗类型,检测方法使用R软件(4.2.2版).
结果：共纳入16项研究，共1725例患者。14项研究评估了基线ctDNA状态与患者预后之间的关联。无论转移状态如何，ctDNA水平升高的患者的DFS（HR=6.26;95％CI，3.71-10.58，P<0.001）和OS（HR=4.23;95％CI，2.72-6.57，P<0.001）均显着降低。ctDNA采样时间，治疗类型和检测方法。六项研究评估了ctDNA动力学在UC中的预后价值。在治疗或观察期间显示ctDNA水平降低或清除的患者表现出更有利的DFS（HR=0.26，95％CI，0.17-0.41，P<0.001）和OS（HR=0.21，95％CI，0.11-0.38，P<0.001）。基于转移状态和检测方法的亚组分析中的关联保持一致。在免疫检查点抑制剂治疗的环境中，基线ctDNA水平较低和治疗期间ctDNA减少均与更有利的肿瘤学结局显著相关.此外，ctDNA中鉴定的FGFR3等特定基因突变在UC患者中也具有预测价值.
结论：本荟萃分析显示ctDNA状态及其动态变化与UC患者的生存结局密切相关，提示在这种情况下，ctDNA检测在预后预测和决策中具有重要的临床实用性。
