A Contemporary Review of Resectability and Treatment Strategies for Colorectal Liver Metastases: Part 1—Diagnosis, Defining Resectability, and Management of Upfront Resectable and Synchronous Disease

Background/Objectives: Colorectal liver metastases (CRLMs) remain a major determinant of long-term outcome. Although hepatic resection offers the best chance of durable survival, the definition of resectability has evolved beyond technical feasibility alone. This review aims to provide a structured overview of contemporary management strategies for patients with upfront technically resectable or synchronous CRLM, with emphasis on patient selection, tumor biology, perioperative systemic therapy, margin strategy, and surgical sequencing. Methods: A structured literature search of PubMed/MEDLINE, Embase, Scopus, and the Cochrane Library was performed to identify studies published between 2000 and 2026. Eligible studies evaluated surgical, liver-directed, or systemic treatment strategies for CRLMs and reported outcomes including overall survival, disease-free survival, recurrence, margin status, or perioperative morbidity. Given the heterogeneity of the available evidence, findings were synthesized narratively. Results: Contemporary management of CRLMs requires integration of patient fitness, technical resectability, and tumor biology. In upfront technically resectable disease, routine neoadjuvant chemotherapy has not consistently improved overall survival, whereas selected high-risk patients may benefit from short-course preoperative therapy. Margin strategy is increasingly biology-informed rather than based on a universal margin width. In synchronous disease, no single operative sequence is superior for all patients; treatment should be selected according to disease burden, operative complexity, and the need to preserve access to systemic therapy. Conclusions: Management of upfront resectable and synchronous CRLMs should be individualized through multidisciplinary assessment. Current evidence supports a risk-adapted strategy that integrates technical feasibility, patient factors, and tumor biology while recognizing persistent uncertainty regarding optimal chemotherapy timing and surgical sequencing.