Role of Locoregional Therapy on Survival After Living Donor Liver Transplantation for Hepatocellular Carcinoma--Experience from a High-volume Center.

Background: Locoregional therapy (LRT) in patients with hepatocellular carcinoma (HCC) before liver transplantation (LT) has a role in improving the tumor biology and post-LT survival outcome apart from downstaging and bridging. We retrospectively analyzed our database of adult living donor liver transplants (LDLT) for HCC, to compare the survival outcomes in Group-1 (upfront-LT, HCC within Milan/UCSF/AFP<1000 ng/ml) and Group-2 (LT post-LRT, HCC beyond UCSF/irrespective of tumor burden with AFP>1000 ng/ml). We also explored the risk factors for recurrence on follow-up.

Methods: A study group (n = 506, Group-1-348, Group-2 = 158) of patients with HCC who underwent LDLT between July 2006 and December 2022, excluding incidental HCC (n = 42), patients with other histology (n = 13) and in-hospital mortality (n = 43), were analyzed. Study cohort (n = 341), after propensity score matching, was analyzed for survival outcomes (overall survival, OS and disease-free survival, DFS) and risk factors for recurrence between Group-1 (n = 156) and Group-2 (n = 158).

Results: Group-2 exhibited a trend towards better mean OS and DFS compared to Group-1 (OS-133 vs. 107-months,  = NS, DFS-118 vs. 102-months,  = NS). Long-term OS (10-year) for those within Milan and UCSF criteria was superior in Group-2,  = NS. Complete pathological response (cPR) after LRT (46.8%), significantly improved OS and DFS compared to those with partial response and stable disease; 152 vs. 94 vs. 49 months,  = 0.001, and 147 vs. 75 vs. 41 months,  = 0.006, respectively. Recipient age, size of tumor, and pre-LT serum alpha-fetoprotein (AFP) were independent predictors of cPR. Independent risk factors for recurrence included pre-LT AFP, tumors beyond UCSF, perineural invasion, and high-grade tumors.

Conclusion: Locoregional therapy in HCC offers significantly better OS and DFS in those who had a complete pathological response. Risk factors for recurrence post-LT were AFP level, beyond UCSF tumors, and high-grade HCC with PNI on histology.