Association of Pre-Transplant Tyrosine Kinase Inhibitor Therapy With Tumor Response and Survival in Hepatocellular Carcinoma: A 10-Year Retrospective Cohort Study of 427 Patients.

BACKGROUND

Patients with hepatocellular carcinoma (HCC) awaiting liver transplantation remain at risk of tumor progression during the waiting period, highlighting the need for effective bridging or downstaging strategies. Although tyrosine kinase inhibitors (TKIs) are widely used in advanced HCC, their role in the pre-transplant setting remains unclear. This study evaluated the association of pre-transplant TKI therapy with survival, tumor response, and safety in HCC patients undergoing liver transplantation.

METHODS

We retrospectively analyzed 427 patients with HCC who underwent orthotopic liver transplantation (OLT) between January 2015 and December 2024. Two separate propensity score matching (PSM) analyses were performed to compare outcomes between patients with and without pre-transplant TKI therapy, and to evaluate the additional association of TKIs among patients receiving transarterial chemoembolization (TACE). Primary outcomes were overall survival (OS) and recurrence-free survival (RFS). Tumor response and safety were also assessed.

RESULTS

After PSM, 160 matched patients were included in the primary analysis. Pre-transplant TKI therapy was associated with longer RFS (log-rank p < 0.05) and lower recurrence rates (p = 0.007), greater pathological tumor necrosis (p < 0.001), and higher radiological response rates (all p < 0.05). Higher 5- and 10-year OS and RFS rates were also observed in the TKIs group (all p < 0.05). On multivariable analysis, pre-transplant TKI therapy remained associated with lower recurrence risk but not OS. Exploratory subgroup analyses suggested that these associations were more evident in patients beyond conventional transplant criteria. Among 120 matched patients receiving TACE, combined TACE and TKI therapy was associated with better survival and tumor response (all p < 0.05). Palmar-plantar erythrodysesthesia occurred more frequently in the TKIs group (p = 0.035), whereas major perioperative complications were comparable between groups, although ICU stay was slightly longer in the TKIs group (p = 0.034).

CONCLUSIONS

Pre-transplant TKI therapy, particularly when combined with TACE, was associated with better tumor response and favorable long-term outcomes without an apparent increase in major perioperative risk. These associations appeared more evident in patients beyond conventional transplant criteria. Prospective studies are needed to further validate these findings.

TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov (registry number NCT07418138).