Incorporating Tumor Biology to Predict Hepatocellular Carcinoma Recurrence in Patients Undergoing Living Donor Liver Transplantation Using Expanded Selection Criteria

Abstract

Conventional selection criteria for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) are based on tumour size/number only, and do not consider vital surrogates of tumor biology such as alpha-fetoprotein (AFP) and tumor [¹⁸ F]fluorodeoxyglucose positron emission tomography ([¹⁸ F]FDG PET) avidity. We analyzed survival outcomes, and predictors of HCC recurrence in 405 patients with cirrhosis and HCC (HCC-cirr) who underwent living donor LT (LDLT) using our expanded selection criteria: no extrahepatic disease or major vascular invasion, irrespective of tumor size/number. Fifty-one percent patients had tumours beyond Milan, and 43% beyond the University of California San Francisco [UCSF] criteria. The 5-year overall survival (OS) and recurrence-free survival (RFS) were 64% and 70%, respectively. Three preoperatively available factors predicted recurrence: pre-LT AFP ≥100 ng/mL (P = 0.005; hazard ratio [HR], 2.190), tumor burden beyond the UCSF criteria (P = 0.001; HR, 2.640), and [¹⁸ F]FDG PET avidity (P = 0.004; HR, 2.442). A prognostic model based on the number and combination of the aforementioned preoperative risk factors was developed using a competing-risk RFS model. Three risk groups were identified: low (none or a single risk factor present, 9.3% recurrence), moderate (AFP ≥100 ng/mL and [¹⁸ F]FDG PET avidity, or beyond UCSF tumor and [¹⁸ F]FDG PET avidity, 25% recurrence), and high (AFP ≥100 ng/mL and beyond UCSF, or presence of all 3 risk factors, 46% recurrence). Acceptable long-term outcomes were achieved using our expanded selection criteria. Our prognostic model to predict recurrence based on preoperative biological and morphological factors could guide pretransplant management (downstaging versus upfront LDLT) with the aim of reducing post-LDLT recurrence.