SYSTEMATIC REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Prognostic value of baseline circulating tumor DNA levels in metastatic castration-resistant prostate cancer: A systematic review and meta-analysis
1. Sun Yat-Sen University, Guangzhou, China
2. Guangxi Medical University, Nanning, China
3. China Pharmaceutical University, Nanjing, China
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Abstract
Background: Metastatic castration-resistant prostate cancer (mCRPC) remains a clinically aggressive and lethal disease. Circulating tumor DNA (ctDNA), as a minimally invasive biomarker, has shown prognostic utility in several solid tumors. However, its clinical relevance in mCRPC has not been comprehensively elucidated. Methods: A systematic search of PubMed and EMBASE was conducted from inception to July 2025 to identify studies evaluating the prognostic impact of baseline ctDNA levels in patients with mCRPC. Eligible studies reported associations between ctDNA levels and survival outcomes. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for overall survival (OS), progression-free survival (PFS), radiographic PFS (rPFS), and prostate specific antigen PFS (PSA-PFS) using random-effects models. Results: Twenty-four studies encompassing 5,272 patients met the inclusion criteria. Elevated baseline ctDNA levels were significantly associated with inferior OS (HR: 3.45; 95% CI: 2.77–4.31), PFS (HR: 2.26; 95% CI: 1.74–2.93), rPFS (HR: 2.39; 95% CI: 1.85–3.10), and PSA-PFS (HR: 2.50; 95% CI: 1.81–3.46). Subgroup analyses showed that the negative prognostic impact of high baseline ctDNA levels on OS remained consistent regardless of detection methods, treatment types, and stratification strategies. Conclusion: High baseline ctDNA levels—regardless of measurement approach or therapeutic context—are associated with markedly worse clinical outcomes in mCRPC. These findings highlight ctDNA as a clinically meaningful, noninvasive prognostic biomarker, supporting its integration into personalized risk stratification frameworks and therapeutic decision-making in mCRPC.
Summary
Keywords
biomarker, circulating tumor DNA, Meta-analysis, metastatic castration-resistant prostate cancer, Survival outcomes
Received
23 August 2025
Accepted
17 February 2026
Copyright
© 2026 Lin, Liao, Luo and Shen. 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: Jinhai Shen
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