Circulating tumor DNA as a biomarker of prognosis prediction in colorectal cancer: a systematic review and meta‐analysis

Objective: Circulating tumor DNA (ctDNA) is increasingly being used as a potential biomarker in colorectal cancer (CRC) patients. However, the role of ctDNA in CRC prognosis prediction remains unclear. The objective is to systematically assess the clinical value of ctDNA in colorectal cancer prognos...

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Main Authors: Qingxin Zhou, Xiaowei Chen, Baoqi Zeng, Meng Zhang, Nana Guo, Shanshan Wu, Hongmei Zeng, Feng Sun
Format: Article
Language:English
Published: Elsevier 2025-04-01
Series:Journal of the National Cancer Center
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Online Access:http://www.sciencedirect.com/science/article/pii/S2667005424001169
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author Qingxin Zhou
Xiaowei Chen
Baoqi Zeng
Meng Zhang
Nana Guo
Shanshan Wu
Hongmei Zeng
Feng Sun
author_facet Qingxin Zhou
Xiaowei Chen
Baoqi Zeng
Meng Zhang
Nana Guo
Shanshan Wu
Hongmei Zeng
Feng Sun
author_sort Qingxin Zhou
collection DOAJ
description Objective: Circulating tumor DNA (ctDNA) is increasingly being used as a potential biomarker in colorectal cancer (CRC) patients. However, the role of ctDNA in CRC prognosis prediction remains unclear. The objective is to systematically assess the clinical value of ctDNA in colorectal cancer prognosis prediction throughout the treatment cycle. Methods: PubMed, Web of Science, Embase, Cochrane Library, Scopus, and clinical trials.gov database was searched from January 2016 to April 2023. Observational studies and randomized clinical trials reporting on ctDNA and prognostic outcomes in CRC patients were included. Pooled hazard risk ratios (HRs) were calculated for the primary outcomes, relapse-free survival (RFS), and overall survival (OS). Random-effects models were preferred considering the potential heterogeneity. Results: Sixty-five cohort studies were included. Association between ctDNA and shorter RFS or OS was significant, especially after the full-course treatment recommended by the guidelines (HR = 8.92 [ 95 % CI: 6.02–13.22], P < 0.001, I2 = 73 %; HR = 3.05 [ 95 % CI: 1.72–5.41], P < 0.001, I2 = 48 %) for all types of CRC patients. Despite the presence of heterogeneity, subgroup analyses showed that the cancer type and ctDNA detection assays may be the underlying cause. Besides, ctDNA may detect recurrence earlier than radiographic progression, but no uniform sampling time point between studies might bring bias. However, ctDNA detection did not appear to correlate with pathological complete response achievement in patients with locally advanced rectal cancer. Conclusion: ctDNA detection was significantly associated with poorer prognosis. The potential applications in prognostic prediction are promising and remain to be evaluated in other fields.
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spelling doaj-art-dbff949077944854aac4b9b8b7dd7d202025-08-20T02:16:02ZengElsevierJournal of the National Cancer Center2667-00542025-04-015216717810.1016/j.jncc.2024.05.007Circulating tumor DNA as a biomarker of prognosis prediction in colorectal cancer: a systematic review and meta‐analysisQingxin Zhou0Xiaowei Chen1Baoqi Zeng2Meng Zhang3Nana Guo4Shanshan Wu5Hongmei Zeng6Feng Sun7Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China; Tianjin Centers for Disease Control and Prevention, Tianjin, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China; Central Laboratory, Tianjin Fifth Central Hospital (Peking University Binhai Hospital), Tianjin, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, ChinaHebei Centers for Disease Control and Prevention, Hebei, ChinaClinical Epidemiology and EBM Unit, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, ChinaNational Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China; Key Laboratory of Major Disease Epidemiology, Ministry of Education (Peking University), Beijing, China; Xinjiang Medical University, Xinjiang Uygur Autonomous Region, China; Corresponding author.Objective: Circulating tumor DNA (ctDNA) is increasingly being used as a potential biomarker in colorectal cancer (CRC) patients. However, the role of ctDNA in CRC prognosis prediction remains unclear. The objective is to systematically assess the clinical value of ctDNA in colorectal cancer prognosis prediction throughout the treatment cycle. Methods: PubMed, Web of Science, Embase, Cochrane Library, Scopus, and clinical trials.gov database was searched from January 2016 to April 2023. Observational studies and randomized clinical trials reporting on ctDNA and prognostic outcomes in CRC patients were included. Pooled hazard risk ratios (HRs) were calculated for the primary outcomes, relapse-free survival (RFS), and overall survival (OS). Random-effects models were preferred considering the potential heterogeneity. Results: Sixty-five cohort studies were included. Association between ctDNA and shorter RFS or OS was significant, especially after the full-course treatment recommended by the guidelines (HR = 8.92 [ 95 % CI: 6.02–13.22], P < 0.001, I2 = 73 %; HR = 3.05 [ 95 % CI: 1.72–5.41], P < 0.001, I2 = 48 %) for all types of CRC patients. Despite the presence of heterogeneity, subgroup analyses showed that the cancer type and ctDNA detection assays may be the underlying cause. Besides, ctDNA may detect recurrence earlier than radiographic progression, but no uniform sampling time point between studies might bring bias. However, ctDNA detection did not appear to correlate with pathological complete response achievement in patients with locally advanced rectal cancer. Conclusion: ctDNA detection was significantly associated with poorer prognosis. The potential applications in prognostic prediction are promising and remain to be evaluated in other fields.http://www.sciencedirect.com/science/article/pii/S2667005424001169Colorectal cancerCirculating tumor DNAPrognostic biomarkerPrognosis predictionMeta-analysis
spellingShingle Qingxin Zhou
Xiaowei Chen
Baoqi Zeng
Meng Zhang
Nana Guo
Shanshan Wu
Hongmei Zeng
Feng Sun
Circulating tumor DNA as a biomarker of prognosis prediction in colorectal cancer: a systematic review and meta‐analysis
Journal of the National Cancer Center
Colorectal cancer
Circulating tumor DNA
Prognostic biomarker
Prognosis prediction
Meta-analysis
title Circulating tumor DNA as a biomarker of prognosis prediction in colorectal cancer: a systematic review and meta‐analysis
title_full Circulating tumor DNA as a biomarker of prognosis prediction in colorectal cancer: a systematic review and meta‐analysis
title_fullStr Circulating tumor DNA as a biomarker of prognosis prediction in colorectal cancer: a systematic review and meta‐analysis
title_full_unstemmed Circulating tumor DNA as a biomarker of prognosis prediction in colorectal cancer: a systematic review and meta‐analysis
title_short Circulating tumor DNA as a biomarker of prognosis prediction in colorectal cancer: a systematic review and meta‐analysis
title_sort circulating tumor dna as a biomarker of prognosis prediction in colorectal cancer a systematic review and meta analysis
topic Colorectal cancer
Circulating tumor DNA
Prognostic biomarker
Prognosis prediction
Meta-analysis
url http://www.sciencedirect.com/science/article/pii/S2667005424001169
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