Current and Future Perspectives of Adjuvant Therapy for Resected Colorectal Liver Metastases

The liver is the most common site of metastatic disease in patients with colorectal cancer. However, the multidisciplinary management of colorectal liver metastases (CLMs) remains suboptimal. Over the past several decades, numerous randomized trials have evaluated the efficacy of adjuvant chemotherapy following CLM resection, revealing improvements in disease-free survival. Nevertheless, these studies have not consistently demonstrated benefits in overall survival, resulting in controversy with regard to the role of routine postoperative chemotherapy. Circulating tumor DNA (ctDNA) has recently emerged as a promising biomarker for detecting molecular residual disease after surgery. Multiple studies have consistently shown that postoperative ctDNA positivity is strongly associated with inferior recurrence-free survival and overall survival in patients with colorectal cancer. In addition to its prognostic value, ctDNA may also assist in guiding postoperative therapeutic decisions. In prospective observational studies of CLM, adjuvant chemotherapy provided potential clinical benefits primarily in patients with ctDNA-positive disease, whereas limited benefits were observed in ctDNA-negative patients. These findings suggest that ctDNA-based detection of molecular residual disease may aid in developing a framework for risk-adapted postoperative management after CLM resection. However, several challenges remain, including the identification of an optimal treatment regimen for ctDNA-positive patients and the improvement of ctDNA assay sensitivity. Ongoing biomarker-driven clinical trials may clarify whether ctDNA-guided strategies can improve patient selection and clinical outcomes following curative resection of CLM.