Sfakianos John P, Basu Arnab, Laliotis George, Cumarasamy Shivaram, Rich Jordan M, Kommalapati Ajitha, Glover Michael, Mahmood Tamara, Tillu Neeraja, Hoimes Christopher J, Selig Grayce, Kollipara Revathi, Stewart Tyler F, Rivero-Hinojosa Samuel, Dutta Punashi, Calhoun Mark, Sharma Shruti, Malhotra Meenakshi, ElNaggar Adam C, Liu Minetta C, Ferguson James E, Diniz Marcio, Mehrazin Reza, Wiklund Peter, Tan Alan, Shah Sumit, Galsky Matthew D
Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
University of Alabama, Birmingham, AL, USA.
Eur Urol Oncol. 2025 Apr;8(2):306-314. doi: 10.1016/j.euo.2024.07.001. Epub 2024 Jul 15.
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.
尽管进行了根治性膀胱切除术（RC），肌层浸润性膀胱癌（MIBC）患者仍有较高的复发风险。迫切需要生物标志物来优化预后评估并选择合适的围手术期全身治疗方案。我们的目的是评估肿瘤信息循环肿瘤DNA（ctDNA）结果在接受RC的多中心膀胱癌患者队列中的预后和预测价值。
我们对167例患者（852份血浆样本）在RC前、分子残留病（MRD；辅助决策）和监测期进行的商业ctDNA检测（Signatera；Natera，美国德克萨斯州奥斯汀）的真实世界数据进行了回顾性分析。我们使用Cox回归分析评估RC前后复发与ctDNA状态之间的相关性。
在研究定义的术后MRD和监测期，与未检测到ctDNA相比，可检测到的ctDNA与无病生存期（DFS）缩短相关（MRD：风险比6.93；p < 0.001；监测期：风险比23.02；p < 0.001）。值得注意的是，ctDNA检测不到的患者似乎未从辅助治疗中获益（p = 0.34）。RC前（p = 0.045）、MRD（p = 0.002）和监测期（p < 0.001）可检测到的ctDNA是与DFS缩短独立相关的唯一危险因素。局限性包括研究的回顾性和非随机性质。
接受RC的膀胱癌患者的ctDNA检测具有预后价值且可能具有预测价值。识别复发高危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。结果显示了针对血液中肿瘤DNA进行肿瘤信息检测对于为每位患者选择最佳治疗方案的价值。
