The Role of Systemic Therapy in Resectable or potentially resectable Colorectal Liver Metastase(s)

The landmark EORTC 40983 trial randomized 364 patients with resectable colorectal liver metastase(s) (up to four liver metastases) to either perioperative treatment with FOLFOX4 (6 cycles before and 6 after surgery) or surgery alone. In patients who underwent resection, chemotherapy improved 3-year disease-free survival (DFS) (HR 0.73; 95% CI: 0.55–0.97), but there was no significant difference in 5-year overall survival (OS), with a higher rate of postoperative complications (25% vs. 16%). The JCOG0603 trial evaluated postoperative FOLFOX (12 cycles of FOLFOX) following resection of metastase(s) and demonstrated an improvement in DFS (HR 0.67; 95% CI: 0.50–0.92), but no improvement in OS. A meta-analysis showed the same results. The decision must be individualized based on an assessment of risks and benefits. The recommendations are to offer perioperative chemotherapy or surgery alone to patients who are candidates for curative resection of liver metastases. For dMMR/MSI-H tumors, immune checkpoint inhibitors are the initial treatment of choice for resectable metastase (NCCN guide line). Systemic therapy is the first-line treatment for unresectable metastases; the choice of treatment regimen depends on MSI status, RAS/BRAF mutation status, and the location of the primary tumor. The primary objectives include prolonging survival