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SYSTEMATIC REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1574449
This article is part of the Research TopicUrothelial Neoplasms: An Integrated Approach to Prevention, Diagnostics, and Personalized TherapyView all 3 articles
Prognostic Significance of Circulating Tumor DNA in Urothelial Carcinoma Patients Undergoing Immune Checkpoint Inhibitor Therapy: A Systematic Review and Meta-Analysis
Provisionally accepted- 1Jinan Central Hospital Affiliated to Shandong First Medical University,Jinan, China, Jinan, China
- 2Department of Hyperbaric Oxygen, Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China., Jinan, China
- 3Department of Neurology, Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China., Jinan, Shandong Province, China
- 4Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China., Jinan, China
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Background: Circulating tumor DNA (ctDNA) has emerged as a novel biomarker with the advantages of being non-invasive and enabling dynamic monitoring, providing significant clinical insights into the prognosis and management of malignancies. However, its prognostic role in patients with urothelial carcinoma (UC) receiving immune checkpoint inhibitors (ICI) remains controversial. This study aims to systematically review and perform a meta-analysis to evaluate the prognostic significance of ctDNA levels in this specific patient population.We conducted a comprehensive search of the PubMed, Cochrane Library, CNKI, and EMBASE databases to include studies published up to November 14, 2024, assessing the prognostic value of ctDNA in UC patients treated with ICI. Fixed-effects or random-effects models were used to evaluate the association between ctDNA levels and overall survival (OS), progression-free survival (PFS)/disease-free survival (DFS). Funnel plots, Begg's test, and Egger's test were employed to assess publication bias.Results: Nine studies from eight articles, comprising a total of 862 urothelial carcinoma (UC) patients treated with immune checkpoint inhibitors (ICIs), were included in this meta-analysis. Seven studies investigated the association between baseline circulating tumor DNA (ctDNA) status and clinical outcomes. Compared to patients without detectable ctDNA, those with elevated baseline ctDNA levels exhibited significantly shorter progression-free survival/disease-free survival (PFS/DFS) (HR = 2.75, 95% CI = 1.36-5.58, P = 0.005), though no statistically significant difference was observed in overall survival (OS) (HR = 2.08, 95% CI = 0.83-5.24, P = 0.119). Additionally, we evaluated the prognostic value of ctDNA dynamics during ICI therapy. A decline or clearance of ctDNA levels was significantly associated with improved clinical outcomes (OS: HR = 0.10, 95% CI = 0.02-0.47, P = 0.004; PFS/DFS: HR = 0.27, 95% CI = 0.16-0.45, P < 0.001).This meta-analysis demonstrates that detectable ctDNA is significantly associated with PFS or DFS in patients with UC undergoing ICI therapy. Moreover, dynamic changes in ctDNA are strongly correlated with OS and PFS/DFS. Therefore, ctDNA serves as a valuable tool for pre-treatment diagnostic assessment and patient stratification and plays a crucial role in monitoring treatment response and tracking disease progression throughout therapy.
Keywords: Urothelial carcinoma (UC), circulating tumor DNA (ctDNA), immune checkpoint inhibitors, Overall survival (OS), Disease-Free Survival, Progression-free survival
Received: 10 Feb 2025; Accepted: 10 Apr 2025.
Copyright: © 2025 Hou, Ma, Ma, Gao and Song. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dan dan Song, Department of Neurology, Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China., Jinan, Shandong Province, China
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