Postoperative circulating tumor DNA for recurrence risk assessment and adjuvant therapy decision-making in resected colorectal cancer: A systematic review and meta-analysis.

Abstract

e15633 Background: Circulating tumor DNA (ctDNA) has emerged as a marker of minimal residual disease after curative-intent resection of colorectal cancer (CRC). While multiple studies have shown an association between postoperative ctDNA positivity and disease recurrence, the magnitude and consistency of this risk remain unclear. The role of ctDNA in informing adjuvant therapy decisions is also still evolving. We therefore conducted a systematic review and meta-analysis to evaluate the prognostic significance of postoperative ctDNA in resected, non-metastatic CRC. Methods: We conducted a systematic search of PubMed, Embase, and the Cochrane Library to identify studies evaluating postoperative ctDNA in resected stage I–III Colorectal Cancer. We included prospective cohorts, randomized trials, and observational studies that reported recurrence-related outcomes according to postoperative ctDNA status. The primary outcome was disease-free or recurrence-free survival. Adjusted hazard ratios (HRs) were collected when available. A random-effects meta-analysis was used to pool HRs and compare outcomes between ctDNA-positive and ctDNA-negative patients. Results: We included ten studies of patients with resected stage I–III colorectal cancer (3 from PubMed, 6 from Embase, and 1 from the Cochrane Library). Across all included studies, postoperative ctDNA positivity was associated with a higher risk of recurrence. In the pooled analysis, patients with detectable postoperative ctDNA had a markedly increased risk of recurrence compared with ctDNA-negative patients (HR 9.3, 95% CI 6.1–14.2; p < 0.001). Although variability between studies was observed (I² ≈82%), this was expected given differences in ctDNA assays and study design. The association between postoperative ctDNA positivity and recurrence was consistent across studies. When individual studies with very large effect estimates were excluded, the overall results remained similar. Several studies also reported use of ctDNA-guided approaches. ctDNA-negative patients were able to avoid adjuvant chemotherapy without increased recurrence, while ctDNA-positive patients represented a high-risk group for relapse. Conclusions: Postoperative ctDNA positivity was strongly associated with an increased risk of recurrence in patients with resected colorectal cancer. Across diverse cohorts and assay platforms, detectable ctDNA after surgery represented patients at higher risk for relapse. While approaches incorporating ctDNA to guide adjuvant therapy varied among studies, our findings support the role of postoperative ctDNA as an important prognostic marker. These results highlight the value of ctDNA for postoperative risk assessment and support ongoing prospective trials to clarify how ctDNA should be incorporated into adjuvant treatment decisions.