A Contemporary Review of Resectability and Treatment Strategies for Colorectal Liver Metastases: Part 2—Advanced Surgical Techniques, Conversion Strategies, and the Expanding Boundaries of Treatment

Background/Objectives: Most patients with colorectal liver metastases (CRLM) present with disease beyond upfront technical resectability. Advances in systemic therapy, surgical technique, and liver-directed therapies have expanded the proportion of patients who can achieve curative-intent treatment, yet substantial heterogeneity in practice persists. This review provides a structured synthesis of current management strategies for borderline resectable, initially unresectable, and never resectable CRLM. Methods: A structured literature search of PubMed/MEDLINE, Embase, Scopus and the Cochrane Library was performed to identify studies published between 2000 and 2026 using the eligibility criteria described in Part 1 of this review. Findings were synthesized narratively across systemic, surgical, and liver-directed treatment strategies. Results: Future liver remnant augmentation through regenerative procedures offers higher rates of conversion to resection in borderline cases. Conversion chemotherapy enables secondary resection in 12–35% of initially unresectable patients, with regimen selection guided by RAS/BRAF status, primary tumor sidedness, and performance status; however, most pivotal trials were designed for the broader metastatic colorectal cancer population, with conversion to resection rarely serving as the primary endpoint. For never resectable liver-only disease, liver transplantation demonstrates survival advantage in highly selected patients and iterative local therapy remains an area of active investigation. Across all settings, achieving complete local treatment remains the strongest determinant of long-term survival. Conclusions: Management of complex CRLM requires individualized, multidisciplinary decision-making with repeated reassessment of resectability throughout treatment. The evidence is constrained by heterogeneous resectability definitions, reliance on trials not designed for CRLM-specific endpoints, and limited data on several emerging strategies. Standardized eligibility frameworks and CRLM-specific trial designs are needed to advance the field.