Impact of Minimal Residual Disease on Early Recurrence of Liver Metastatic Colorectal Cancer

Abstract

For patients with resectable colorectal liver metastases (CRLM), the efficacy of adjuvant chemotherapy remains a subject of debate. Several studies have concluded that postoperative circulating tumor DNA (ctDNA) is a marker of minimal residual disease (MRD) and is a useful prognostic factor in patients with nonmetastatic colorectal cancer. However, few studies have explored its application in cases involving metastases. This was an observational study that included CRLM patients who underwent primary and liver tumor resection. By examining targeted sequencing of 50 genes commonly mutated in CRC, we identified at least one somatic mutation in each patient's metastatic liver tumor. Blood samples were obtained before and 1-month after surgery. Fifty-three patients were included, and recurrence was diagnosed in 39 patients. Of those, 13 patients experienced early relapse. ctDNA was detected in 45 patients before surgery and 11 after. All MRD-positive patients experienced recurrence. Among them, nine had early recurrence. MRD-positive patients had poorer recurrence free survival (RFS, p < 0.0001) and overall survival (OS, p < 0.0005). Nine of 13 patients with early recurrence had MRD; however, two of 40 patients without early recurrence also had MRD (p < 0.0001). Among 42 MRD-negative patients, adjuvant chemotherapy had no impact of RFS (p = 0.84) or OS (p = 0.54). MRD proved valuable in predicting the risk of postoperative recurrence in patients with CRLM, particularly because MRD positivity emerged as a significant risk factor for early recurrence. Furthermore, it appears that adjuvant chemotherapy may not effectively improve the prognosis for MRD-negative patients.