Downstaging hepatocellular carcinoma: A systematic review and pooled analysis

Downstaging can facilitate liver transplantation (LT) for patients outside of Milan criteria with hepatocellular carcinoma (HCC); however, the optimal protocol and downstaging outcomes are poorly defined. We aimed to characterize rates of successful downstaging to within Milan criteria and post-LT recurrence and survival among patients who underwent downstaging. We performed a systematic literature review using the MEDLINE and Embase databases from January 1996 through March 2015 and a search of national meeting abstracts from 2010 to 2014. Rates of downstaging success (defined as a decrease of tumor burden to within Milan) and post-LT recurrence with 95% confidence intervals (CIs) were calculated. Prespecified subgroup analyses were conducted by treatment modality, study design, and patient characteristics. Thirteen studies (n = 950 patients) evaluating downstaging success had a pooled success rate of 0.48 (95% CI, 0.39-0.58%). In subgroup analyses, there was no significant difference comparing transarterial chemoembolization (TACE) versus transarterial radioembolization (TARE; P = 0.51), but there were higher success rates in prospective versus retrospective studies (0.68 versus 0.44; P < 0.001). The 12 studies (n = 320 patients) evaluating post-LT HCC recurrence had a pooled recurrence rate of 0.16 (95% CI, 0.11-0.23). There was no significant difference in recurrence rates between TACE and TARE (P = 0.33). Post-LT survival could not be aggregated because of heterogeneity in survival data reporting. Current data have heterogeneity in baseline tumor burden, waiting time, downstaging protocols, and treatment response assessments. There are also notable limitations including inconsistent reporting of inclusion criteria, downstaging protocols, and outcome assessment criteria. In conclusion, the success rate of downstaging HCC to within Milan criteria exceeds 40%; however, posttransplant HCC recurrence rates are high at 16%. Downstaging protocols for HCC should be systematically studied and optimized to minimize the risk of post-LT HCC recurrence.