O-L05 Do Subsets of Patients with Intrahepatic Cholangiocarcinoma and Combined Hepatocellular-Cholangiocarcinoma Benefit from Transplantation? A Systematic Review, Proportional Meta-Analysis and Meta-Regression

Background Resection remains the main curative treatment option for intrahepatic cholangiocarcinoma (iCCA) and combined hepatocellular-cholangiocarcinoma (cHCC-CCA), however, outcomes are poor. Recent retrospective analyses of patients found to have incidental iCCA and cHCC-CCA following transplantation have suggested that transplantation may be superior to resection. We performed a systematic review and proportional meta-analysis to estimate the benefit of transplantation for iCCA and cHCC-CCA. Methods MEDLINE, EMBASE, Scopus, and Web of Science were searched from January 1990 to December 2020. All studies reporting patients with iCCA and cHCC-CCA undergoing transplantation were identified. A proportional meta-analysis was performed, pooling overall survival (OS), disease-free survival (DFS), and recurrence rates post-transplantation. Sub-group analyses were performed for patients with ‘early’ iCCA, ‘advanced’ iCCA, Goodman type I cHCC-CCA, and Goodman type II cHCC-CCA. Univariable meta-regression was completed assessing the impact of variables reported by at least five studies on OS and DFS at 5-years, as well as recurrence post-transplant. Results Twenty-eight studies including 489 patients were identified (249 with iCCA and 240 with cHCC-CCA). Pooled OS and DFS at 5-years were lower in the iCCA group, 30.2% (95% CI 18.6% – 43.1%) and 29.2% (95% CI 20.4% – 38.9%), compared to the cHCC-CCA group, 55.0% (95% CI 47.2% – 62.8%) and 43.2% (95% CI 30.2% – 56.7%). In the ‘early’ iCCA group, pooled OS at 5-years was 66.5% (95% CI 47.2% – 83.3%). When separated by Goodman type, those with type II tumours reported higher pooled OS, 69.7% (95% CI 57.8% – 80.5%), compared to type I tumours, 61.3% (95% CI 46.1 – 75.5). Univariable meta-regression found only microvascular invasion impacted overall survival at 5-years and recurrence following transplantation in the iCCA group. At 5-years there was a negative correlation between the proportion of patients found to have microvascular invasion and overall survival (Adjusted R2 = 0.89, p = 0.017). There was a positive correlation between the proportion of patients with microvascular invasion on explant pathology and recurrence following transplantation (Adjusted R2 = 0.76, p = 0.047). Conclusions Subsets of patients with iCCA and cHCC-CCA may benefit from liver transplantation. However, further research, including clinical trials exploring transplantation in 'early' disease and in comparison to resection, is required to conclude which subsets of patients will benefit most from transplantation.