尽管进行了根治性膀胱切除术（RC），但肌层浸润性膀胱癌（MIBC）患者的复发风险很高。迫切需要生物标志物来完善预后和选择适当的围手术期全身治疗。我们的目的是评估接受 RC 治疗的多中心膀胱癌患者队列中肿瘤相关的循环肿瘤 DNA (ctDNA) 结果的预后和预测价值。我们对商业 ctDNA 测试的真实世界数据进行了回顾性分析（ Signatera；Natera，奥斯汀，德克萨斯州，美国）在 RC 之前和分子残留疾病（MRD；辅助决策）和监测窗口期间对 167 名患者（852 份血浆样本）进行了检查。我们使用 Cox 回归分析评估了 RC 前后复发与 ctDNA 状态之间的相关性。在研究定义的术后 MRD 和监测窗口期间，与不可检测到的 ctDNA 相比，可检测到的 ctDNA 与较短的无病生存期 (DFS) 相关（MRD：危险）比率 6.93；p < 0.001；监测：风险比 23.02；p < 0.001）。值得注意的是，ctDNA 检测不到的患者似乎并未从辅助治疗中受益 (p = 0.34)。在预 RC (p = 0.045)、MRD (p = 0.002) 和监测 (p < 0.001) 窗口中可检测到的 ctDNA 是与较短 DFS 独立相关的唯一风险因素。该研究的局限性包括回顾性和非随机性。对接受 RC 的膀胱癌患者进行 ctDNA 检测具有预后和潜在的预测作用。识别复发高风险患者可能有助于患者咨询和决策。我们发现肌层浸润性膀胱癌患者的预后与血液样本中肿瘤 DNA 的检测密切相关。结果显示了对血液中肿瘤 DNA 进行肿瘤知情检测对于为每位患者制定最佳治疗决策的价值。版权所有 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。

Despite curative-intent radical cystectomy (RC), patients with muscle-invasive bladder cancer (MIBC) are at high risk of recurrence. Biomarkers are urgently needed to refine prognostication and selection of appropriate perioperative systemic therapies. Our aim was to evaluate the prognostic and predictive value of tumor-informed circulating tumor DNA (ctDNA) results in a multicenter cohort of patients with bladder cancer who underwent RC.We performed a retrospective analysis of real-world data for a commercial ctDNA test (Signatera; Natera, Austin, TX, USA) performed in 167 patients (852 plasma samples) before RC and during molecular residual disease (MRD; adjuvant decision) and surveillance windows. We assessed the correlation between recurrence and ctDNA status before and after RC using Cox regression analysis.During study-defined postoperative MRD and surveillance windows, detectable ctDNA was associated with shorter disease-free survival (DFS) when compared to undetectable ctDNA (MRD: hazard ratio 6.93; p < 0.001; surveillance: hazard ratio 23.02; p < 0.001). Of note, patients with undetectable ctDNA did not appear to benefit from adjuvant therapy (p = 0.34). Detectable ctDNA in the pre-RC (p = 0.045), MRD (p = 0.002), and surveillance (p < 0.001) windows was the only risk factor independently associated with shorter DFS. Limitations include the retrospective and nonrandomized nature of the study.ctDNA testing in patients with bladder cancer undergoing RC was prognostic and potentially predictive. Identification of patients at high risk of recurrence may aid in patient counseling and decision-making.We found that outcomes for patients with muscle-invasive bladder cancer are strongly linked to detection of tumor DNA in blood samples. The results show the value of tumor-informed testing for tumor DNA in blood for decisions on the best treatment for each individual patient.Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.