Meta-analysis and Meta-regression of Survival After Liver Transplantation for Unresectable Perihilar Cholangiocarcinoma

OBJECTIVE:To systematically review studies reporting survival data following neoadjuvant chemoradiation and orthotopic liver transplantation (NCR-OLT) for unresectable perihilar cholangiocarcinoma (pCC). BACKGROUND:Despite survival improvements for other cancers, the prognosis of pCC remains dismal. Since publication of the Mayo protocol in 2000, increasing numbers of series globally are reporting outcomes after NCR-OLT. METHODS:MEDLINE, EMBASE, Scopus, and Web of Science databases were searched from January 2000 to February 2019. A meta-analysis of proportions was conducted, pooling 1, 3-, and 5-year overall survival and recurrence rates following NCR-OLT across centers. Per protocol and intention to treat data were interrogated. Meta-regression was used to evaluate PSC as a confounder affecting survival. RESULTS:Twenty studies comprising 428 patients were eligible for analysis. No RCTs were retrieved; the majority of studies were noncomparative cohort studies. The pooled 1, 3-, and 5-year overall survival rates following OLT without neoadjuvant therapy were 71.2% (95% CI 62.2%–79.4%), 48.0% (95% CI 35.0%–60.9%), and 31.6% (95% CI 23.1%–40.7%). These improved to 82.8% (95% CI 73.0%–90.8%), 65.5% (95% CI 48.7%–80.5%), and 65.1% (95% CI 55.1%–74.5%) if neoadjuvant chemoradiation was completed. Pooled recurrence after 3 years was 24.1% (95% CI 17.9%–30.9%) with neoadjuvant chemoradiation, 51.7% (95% CI 33.8%–69.4%) without. CONCLUSIONS:In unresectable pCC, NCR-OLT confers long-term survival in highly selected patients able to complete neoadjuvant chemoradiation followed by transplantation. PSC patients appear to have the most favorable outcomes. A high recurrence rate is of concern when considering extending national graft selection policy to pCC.