Circulating Tumor DNA as a Real-Time Biomarker for Minimal Residual Disease and Recurrence Prediction in Stage II Colorectal Cancer: A Systematic Review and Meta-Analysis
Silvia Negro, Alessandra Pulvirenti, Chiara Trento, Stefano Indraccolo, Stefania Ferrari, Marco Scarpa, Emanuele Damiano Luca Urso, Francesca Bergamo, Salvatore Pucciarelli, Simona Deidda, Angelo Restivo, Sara Lonardi, Gaya Spolverato
Abstract
The role of adjuvant chemotherapy (adj-CT) in stage II colon cancer remains controversial. Circulating tumor DNA (ctDNA) is a promising biomarker for detecting minimal residual disease (MRD) and predicting recurrence. This systematic review and meta-analysis evaluated the prognostic value of ctDNA in stage II colorectal cancer (CRC), focusing on postoperative detection, post adj-CT outcomes, and dynamic surveillance. A literature search identified studies correlating ctDNA positivity in stage II CRC with recurrence risk, recurrence-free survival (RFS), and disease-free survival (DFS). Seven studies met the inclusion criteria. Postoperative ctDNA positivity significantly increased the risk of recurrence (pooled risk ratio [RR:] 3.66; 95% confidence interval [CI]: 1.25–10.72; p = 0.002). CtDNA positivity after adj-CT was strongly associated with poor survival, while dynamic ctDNA monitoring detected recurrence earlier than conventional methods, including carcinoembryonic antigen (CEA) and imaging. CtDNA is a robust prognostic biomarker in stage II CRC, enabling personalized treatment. High-risk ctDNA-positive patients may benefit from intensified therapy, while ctDNA-negative patients could avoid unnecessary treatments. However, the standardization of detection methods and large-scale validation studies are needed before integrating ctDNA into routine clinical practice as a non-invasive, dynamic tool for personalized care.