The State of the Art on Management of Patients with Unresectable Liver Metastases from Colorectal Cancer.

Colorectal cancer frequently metastasizes to the liver, and a substantial proportion of patients present with unresectable colorectal liver metastases (CRLM), which are associated with limited survival. While systemic chemotherapy remains a central component of management, advances in liver-directed therapies and transplantation have significantly expanded therapeutic possibilities in selected patients. This review provides a comprehensive and up-to-date overview of current management strategies for unresectable CRLM, with a focus on systemic chemotherapy, intra-arterial therapies, and liver transplantation. Systemic chemotherapy plays a central role, either as conversion therapy aimed at achieving secondary resectability or as palliative treatment to prolong survival and maintain quality of life. The integration of targeted agents and molecular profiling has enabled increasingly personalized therapeutic strategies. Liver-directed therapies, including hepatic arterial infusion chemotherapy, transarterial chemoembolization, and radioembolization, provide effective local disease control and may facilitate downstaging in selected patients. In parallel, liver transplantation has re-emerged as a promising option for highly selected patients with liver-only disease, demonstrating encouraging long-term survival in recent prospective studies. However, optimal patient selection, timing, and sequencing of these modalities remain key challenges. The management of unresectable CRLM is evolving toward a multidisciplinary and individualized approach that integrates systemic, locoregional, and transplant-based strategies. In selected patients, this paradigm shift may translate into meaningful survival benefit, although further prospective studies are required to refine indications and optimize treatment sequencing.