Liver transplantation for unresectable colorectal liver metastases: a narrative review

Liver transplantation (LT) for unresectable colorectal liver metastases (uCRLM) initially showed no clear survival advantage in early attempts, leading to waning enthusiasm. Interest was revived in 2013 following the prospective, non-randomized Norwegian Secondary Cancer (SECA) I study, which reported a 5-year overall survival (OS) of 60%-far surpassing outcomes with systemic therapy alone. More recently, the TransMet randomized controlled trial demonstrated a 5-year OS of 73% in the LT-plus-chemotherapy arm vs. 9% with chemotherapy alone, a result comparable to outcomes for established LT indications. This review aims to summarize recent advances and discuss key considerations for implementing LT for uCRLM in clinical practice-particularly patient selection and standardization of protocols.

In this narrative review of currently available reports on the outcomes of LT for uCRLM, we identified eight studies [2017-2025] from European and North American centers.

Four were prospective (including one randomized trial) and three were multicenter. Their protocols varied considerably, especially regarding donor sources (living vs. deceased) and inclusion criteria for factors such as primary tumor laterality, kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status, and metabolic tumor volume. Overall, 3-year OS ranged from 62% to 100%. Recurrence-free survival (RFS) also showed wide variability, with 3-year RFS between 38% and 68.6%. Centers that employed consistent selection protocols typically reported better survival outcomes, underscoring the importance of standardization. Donor availability emerged as a key factor, with living donor LT offering an alternative in regions where deceased donor access is limited-such as North America and parts of Asia. Extended observation periods and stratification by KRAS status or tumor location (right- vs. left-sided) might help refine patient selection.

Although LT for uCRLM is no longer considered purely exploratory, questions remain about the best use of adjuvant chemotherapy. Moving forward, multicenter collaborations, standardized protocols, incorporation of tumor biology insights from resectable CRLM literature, and decision-support strategies (including artificial intelligence) may help optimize patient selection and improve outcomes in this advancing field.