Contemporary management of unresectable or borderline operable colorectal cancer liver metastases: a review and modern treatment algorithm

BACKGROUND: Colorectal liver metastases are common, and the degree of liver tumor often determines overall prognosis. Advances in systemic therapy, surgical technique, locoregional therapies, and transplant oncology have expanded the curative-intent treatment options for patients with upfront unresectable colorectal liver metastases (uCRLM). STUDY DESIGN: This narrative review synthesizes the contemporary evidence regarding the management of unresectable or borderline resectable CRLM, with a focus on microsatellite-stable disease. RESULTS: The modern management of uCRLM requires integration of systemic therapy with liver-directed strategies, including ablation, transarterial therapies, hepatic artery infusion chemotherapy, staged hepatectomy techniques, and liver transplantation. Patient selection increasingly emphasizes tumor biology, response to therapy, and adequacy of future liver remnant rather than strict anatomic criteria. Emerging strategies such as combined portal and hepatic vein embolization, multimodal cytoreduction, and transplant-based approaches have further expanded treatment options. CONCLUSIONS: The management of unresectable CRLM has evolved into a dynamic, multidisciplinary field. This review provides a practical, evidence-informed framework to guide treatment sequencing and patient selection, emphasizing the importance of multidisciplinary evaluation and early referral to experienced centers.