Liver transplantation is an effective treatment for small, unresectable hepatocellular carcinomas in patients with cirrhosis.

RFA is a safe and effective treatment of small HCC in cirrhotics awaiting OLT, although tumor size (>3 cm) and time from treatment (>1 year) predict a high risk of tumor persistence in the targeted nodule. RFA should not be considered an independent therapy for HCC.

Selection criteria and benefit of liver transplantation for hepatic metastases from neuroendocrine tumors (NETs) remain uncertain. Eighty-eight consecutive patients with metastatic NETs eligible for liver transplantation according to Milan-NET criteria were offered transplant (n = 42) versus nontransplant options (n = 46) depending on list dynamics, patient disposition, and age. Tumor burden between groups did not differ. Transplant patients were younger (40.5 vs. 55.5 years; p < 0.001). Long-term outcomes were compared after matching between groups made on multiple Cox models adjusted for propensity score built on logistic models. Survival benefit was the difference in mean survival between transplant versus nontransplant options. No patients were lost or died without recurrence. Median follow-up was 122 months. The transplant group showed a significant advantage over nontransplant strategies at 5 and 10 years in survival (97.2% and 88.8% vs. 50.9% and 22.4%, respectively; p < 0.001) and time-to-progression (13.1% and 13.1% vs. 83.5% and 89%; p < 0.001). After adjustment for propensity score, survival advantage of the transplant group was significant (hazard ratio = 7.4; 95% confidence interval (CI): 2.4-23.0; p = 0.001). Adjusted transplant-related survival benefit was 6.82 months (95% CI: 1.10-12.54; p = 0.019) and 38.43 months (95% CI: 21.41-55.45; p < 0.001) at 5 and 10 years, respectively. Liver transplantation for metastatic NETs under restrictive criteria provides excellent long-term outcome. Transplant-related survival benefit increases over time and maximizes after 10 years.

Background. Liver transplantation cures hepatocellular carcinoma (HCC) if within conventional selection criteria. Expanded criteria are elusive. Loco-regional treatments pursue tumor downstaging from outside Milan criteria to within criteria. No trial investigated HCC-downstaging strategy to expand transplant eligibility. Methods. This multi-center trial aimed at comparing successfully downstaged HCC followed by transplantation vs. non-transplant therapies. Eligible patients had good liver function (Child-Pugh A-B7), HCC beyond Milan, 5-year estimated post-transplant survival ≥50%, no macrovascular or extrahepatic spread. Only partial-complete responses according to modified-RECIST were randomized 1:1 after 3 months observation period, during which sorafenib was allowed. Co-endpoints were survival and timeto-tumor event. We used Kaplan-Meier method, log-rank test, Cox regression for intention-to-treat analysis. Survival benefit was the difference between groups mean survival time. Organ allocation policy changed over time and limited patients' accrual to 4 years. After 4 additional years conditional power calculation estimated the probability that the final results would be statistically significant in the remaining study, given the data observed. ClinicalTrials.gov NCT01387503. Findings. 74 patients were enrolled between March 2011 to March 2015: 29 dropped-out pre-randomization. Downstaging median duration was 6 months (1-17). Success-rate was 73%. Progression during observation was 17%. 45 patients were randomized: 23 transplanted vs. 22 controls. Median followup was 71 months (IQR 60-85). 5-year overall survival was 77.5% (95%CI 61.9-97.1%) in transplants vs. 31.2% (95%CI: 16.6-58.5%) in controls (Cox hazard ratio [HR] 0.22, 95%CI: 0.08-0.61; p=0.004). 5-year tumor eventfree survival was 76.8 (95%CI: 60.8-96.9%) vs. 18.3% (95%CI: 7.1-47.0%) in controls (HR: 0.14, 95%CI: 0.05-0.38; p<0001). 5-year survival-benefit favored transplantation by 14.5 months (95%CI: 3.6-25.3; p=0.009). The trial retained a conditional power of 98.6%. Interpretation. After effective and sustained downstaging of eligible HCCs beyond Milan criteria, liver transplantation is superior to nontransplant therapies. Post-downstaging tumor response should contribute to HCC transplant criteria expansion. Funding. Italian Ministry of Health