Circulating tumor DNA as a biomarker for the prediction of minimal residual disease and the individualization of adjuvant therapy in colorectal cancer - a review of current evidence and perspectives.

BACKGROUND

Colorectal cancer (CRC) remains one of the most common malignancies in the Czech Republic. Despite advances in surgical treatment, the risk of recurrence persists, mainly due to minimal residual disease (MRD). Current surveillance strategies, including colonoscopy, CT imaging, and serum tumor markers (CEA, CA19-9), demonstrate limited sensitivity and specificity. In recent years, circulating tumor DNA (ctDNA) has emerged as a promising biomarker with significant prognostic and predictive potential.

METHODOLOGY: This review was prepared based on a systematic literature search in PubMed, Web of Science, ScienceDirect, Scopus, and clinicaltrials.gov covering the period 2005-2025. Observational studies, retrospective analyses, and randomized clinical trials evaluating the prognostic and predictive role of ctDNA in patients with CRC were included.

RESULTS

Available studies confirm that the presence of ctDNA after curative resection of CRC is a strong predictor of early recurrence and worse survival, whereas ctDNA negativity reliably identifies patients at low risk. Prospective projects (VICTORI, GALAXY, COSMOS) demonstrated that ctDNA can predict relapse several months earlier than standard methods. The BESPOKE CRC study highlighted that only patients with positive ctDNA significantly benefit from adjuvant chemotherapy. The randomized DYNAMIC trial proved that a ctDNA-guided approach enables safe de-escalation of adjuvant therapy without compromising outcomes. Ongoing studies (PEGASUS, SAGITTARIUS, TRACC, DYNAMIC-III, ALTAIR, VEGA) are testing the efficacy of escalation and de-escalation strategies.

CONCLUSIONS

ctDNA is a highly promising biomarker for early MRN detection, risk stratification, and the individualization of adjuvant therapy in CRC patients. Its implementation in routine clinical practice, however, requires confirmation from ongoing randomized trials and validation in the Czech setting, where the use of ctDNA currently remains limited primarily to research.