To test the feasibility of our approach for early prediction of disease recurrence in clinical settings, 104 serial plasma samples of 14 patients with advanced CRC (stages II-IV) and relapse during adjuvant therapy post-tumor resection were retrospectively analyzed for the detection of known hot spot mutations (KRAS, NRAS, and TP53) in cfDNA and compared to imaging-based surveillance. The gene discussed is KRAS; the disease is neoplasm.