Association between bridging therapy and post-transplant outcomes in patients with hepatocellular carcinoma within Milan criteria: A systematic review and meta-analysis

Introduction: Liver transplantation is the curative therapy of choice for patients with early-stage hepatocellular carcinoma (HCC). Locoregional therapies (LRT) are often employed as a bridge to reduce the risk of waitlist dropout; however, their association with post-transplant outcomes is unclear. Methods: We conducted a systematic review using Ovid MEDLINE and EMBASE to identify studies published between database inception and August 2, 2023, which reported post-transplant recurrence-free survival (RFS) and overall survival (OS) among patients transplanted for HCC within Milan criteria, stratified by receipt of bridging therapy. Pooled hazard ratios were calculated for each outcome using the DerSimonian and Laird method for a random-effects model. Results: We identified 38 studies, including 19,671 patients that received and 20,148 patients that did not receive bridging therapy. Bridging therapy was not associated with significant differences in RFS (pooled HR 0.91, 95%CI 0.77-1.08; I-2=39%) or OS (pooled HR 1.09, 95%CI 0.95-1.24; I-2=47%). Results were relatively consistent across subgroups, including geographic location and study period. Studies were discordant regarding differential strength of association by pre-treatment tumor burden and pathologic response, but potential benefits of LRT were mitigated in those who received 3 or more treatments. Adverse events were reported in a minority of studies, but when reported occurred in 6-15% of patients. Few studies reported loss to follow-up and most had risk of residual confounding. Conclusion: Bridging therapy is not associated with improvements in post-transplant recurrence-free or overall survival among patients with HCC within Milan criteria. The risk-benefit ratio of bridging therapy likely differs based on risk of waitlist dropout.