Prognostic role of postoperative circulating tumor DNA in metastatic colorectal cancer treated with curative intent: A systematic review and meta-analysis.

BACKGROUND

Postoperative circulating tumor DNA (ctDNA) is an emerging biomarker for molecular residual disease (MRD) detection in early-stage colorectal cancer (CRC). However, its prognostic value in patients with resected metastatic disease has not been comprehensively assessed. This study aimed to evaluate the association between postoperative ctDNA detection and survival outcomes, including after completion of adjuvant chemotherapy (post-ACT), in patients with metastatic CRC (mCRC) treated with curative intent.

METHODS

A systematic search of PubMed/MEDLINE, Scopus, and Embase was conducted up to March 17, 2025. Eligible studies included adults with mCRC undergoing curative intent treatment, reporting hazard ratios (HRs) for time-to-event outcomes according to postoperative ctDNA status. Random-effects meta-analyses were performed to pool HRs for recurrence-free survival (RFS) and overall survival (OS). Risk of bias was assessed using the QUIPS tool. The study followed PRISMA guidelines and was registered in PROSPERO (CRD42024528320).

RESULTS

Sixteen studies (N = 1048) were included. Postoperative ctDNA positivity was detected in 409 patients (39.0%) and was associated with significantly worse RFS (16 studies; HR = 4.45, 95% CI, 3.44-5.75; P < 0.0001) and shorter OS (9 studies; HR = 6.23; 95% CI, 3.15-12.33, P = 0.0003). Notably, post-ACT ctDNA positivity (N = 96, 41.4%) remained associated with recurrence (5 studies; HR, 6.08; 95% CI, 4.04-9.16; P < 0.001).

CONCLUSIONS

Postoperative ctDNA positivity in mCRC treated with curative intent is strongly associated with increased risk of recurrence and mortality. These findings support its role as a consistent prognostic biomarker and highlight the need for biomarker-guided clinical trials in this setting.