Liquid biopsy in colorectal cancer: redefining surgical decision-making

Liquid biopsy (LB) has rapidly emerged as a minimally invasive approach to detecting tumor-derived material in the bloodstream, including circulating tumor DNA (ctDNA), circulating tumor cells, and extracellular vesicles. For colorectal surgeons, LB offers a dynamic measure of tumor biology that complements pathological staging and guides postoperative management beyond conventional anatomy-based risk stratification. A scoping review was conducted to evaluate the clinical implications of liquid biopsy in colorectal cancer. PubMed, EMBASE, and the Cochrane Library were systematically searched. Eligible human studies evaluated the diagnostic, prognostic, predictive, perioperative, treatment-monitoring, or surveillance applications of liquid biopsy in colorectal surgical oncology. In localized colon cancer, postoperative ctDNA detection is a marker of minimal residual disease, identifies patients at high risk of recurrence, and supports tailored adjuvant chemotherapy, enabling multiple trials evaluating de-escalation and escalation strategies based on postoperative LB. In rectal cancer, ctDNA kinetics during total neoadjuvant therapy predict pathological response and may guide identification of the optimal candidate for organ-preserving strategies. In metastatic CRC, plasma genotyping enables real-time assessment of RAS/BRAF/HER2/MSI status and, in later lines, supports anti-EGFR rechallenge when resistant clones decline. An increase in ctDNA levels detected through longitudinal monitoring anticipates relapse up to 9 months before radiographic evidence, enabling earlier intervention and potential surgical rescue. LB represents a paradigm shift in surgical oncology, integrating molecular data into perioperative care and surveillance. By aligning operative strategy with biological risk, colorectal surgeons can move toward truly personalized, molecularly guided surgery.