Systemic adjuvant and perioperative chemotherapy following curative-intent liver metastasectomy in colorectal cancer—is it justified?

Colorectal liver metastases (CRLM) pose a significant challenge in oncological care, with surgical resection offering the best chance for long-term survival. Despite curative-intent liver metastasectomy, recurrence rates remain high, underscoring the need for effective adjuvant therapies. While adjuvant chemotherapy (AC) improves disease-free survival (DFS), evidence supporting its overall survival (OS) benefit is limited. This manuscript critically evaluates the role of AC following CRLM resection, with a focus on patient-specific factors influencing treatment outcomes across distinct clinical scenarios. The lack of stratification by molecular biomarkers in prior trials highlights a critical gap in current evidence. Future research should integrate biomarker-driven approaches, leverage circulating tumor DNA (ctDNA) for treatment stratification, and explore novel therapies, including immunotherapies and targeted agents, in both perioperative and adjuvant settings.