Predictive and Prognostic Biomarkers of Recurrence in Locoregional Colorectal Cancer.

Colorectal cancer (CRC) remains a major global health challenge, as recurrence and metastasis continue to significantly impact patient survival and management, especially in cases of locoregional disease. In this regard, identifying reliable predictive and prognostic biomarkers is essential not only for improving therapeutic strategies but also for personalizing treatment plans and guiding post-treatment surveillance. This article comprehensively reviews histological, genetic, microRNA (miRNA), circulating tumor cell (CTC), and serological biomarkers, all of which are closely linked to recurrence and metastatic progression in locoregional CRC.On the one hand, histological markers, such as tumor budding and lymphovascular invasion, offer crucial prognostic insights regarding disease aggressiveness. On the other hand, genetic alterations, including mutations in KRAS, BRAF, and TP53 genes, serve as predictive indicators for therapeutic response as well as risk of recurrence. Moreover, specific miRNAs, such as miR-21, have emerged not only as diagnostic but also as prognostic tools due to their association with metastasis and chemoresistance. Furthermore, circulating tumor cells and cell-free DNA (cfDNA) released by tumors into the bloodstream represent non-invasive biomarkers that are useful for the early detection of micrometastatic disease and real-time monitoring of therapeutic efficacy. Additionally, serological markers, including carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9), continue to play key roles in the routine surveillance of CRC. Integrating these biomarkers into clinical practice thus holds significant potential to stratify patients at high risk of recurrence and guide personalized therapeutic approaches, ultimately improving outcomes for CRC patients. This review consolidates recent findings and underscores the ongoing need for further studies to validate these biomarkers across larger patient cohorts and various CRC stages.