Prognostic significance of circulating tumor DNA in urothelial carcinoma: a systematic review and meta-analysis

Haoyang Liu; Junru Chen; Yuchen Huang; Yaowen Zhang; Yuchao Ni; Nanwei Xu; Fengnian Zhao; Yanfeng Tang; Haolin Liu; Guangxi Sun; Pengfei Shen; Zhenhua Liu; Jin Huang; Banghua Liao; Hao Zeng

doi:10.1097/JS9.0000000000001372

Prognostic significance of circulating tumor DNA in urothelial carcinoma: a systematic review and meta-analysis

Int J Surg. 2024 Apr 3. doi: 10.1097/JS9.0000000000001372. Online ahead of print.

Authors

Affiliations

¹ Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, China.
² Department of Cardiothoracic Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China.
³ Medical Device Regulatory Research and Evaluation Center, West China Hospital, Sichuan University, Chengdu, 610041, China.

PMID: 38573063
DOI: 10.1097/JS9.0000000000001372

Abstract

Background: Circulating tumor DNA (ctDNA) has emerged as a non-invasive 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 sixteen 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.

Conclusion: 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.