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 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.