Role of Immunotherapy for Liver and Biliary Tract Cancers in the Peri-Surgical Setting, a review.

Abstract

Primary liver malignancies, specifically hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), present a substantial global health burden with rising incidence and mortality rates. While surgical interventions offer curative potential, most patients eventually require systemic therapy. Traditional treatments, such as kinase inhibitors and cytotoxic chemotherapy, have historically provided limited efficacy and significant toxicity. Recently, immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 and CTLA-4 pathways have revolutionized the management of advanced liver cancers, demonstrating superior overall survival and durable responses in landmark trials such as IMbrave150 and TOPAZ-1.
This review evaluates the biological rationale and emerging clinical evidence for the use of immunotherapy in the peri-liver transplant (peri-LT) setting. In the pre-LT setting, ICIs have shown promise for tumor downstaging and as a bridge to transplantation, with high objective response rates and successful conversion to transplant eligibility in some cohorts. However, the integration of immunotherapy into transplant protocols presents a unique challenge of balancing potent anti-tumor immunity with the need for post-transplant immunosuppression to prevent allograft rejection.
Current data from retrospective series indicate allograft rejection rates between 26% and 28%, which are largely comparable to general transplant populations, though the clinical severity of these episodes, including potential graft loss, remains a concern. The duration of the washout period between the last ICI dose and transplantation is a critical determinant of safety, with longer intervals (typically >30 to 90 days) associated with a reduced risk of rejection. In the post-LT setting, ICIs may be considered for systemic recurrence, though they carry a high risk of rejection, potentially mitigated by biomarkers like graft PD-L1 expression. Standardized, evidence-based guidelines are necessary to optimize the safety and efficacy of immunotherapy in transplant oncology.