Hypoalbuminemia Is a Hepatocellular Carcinoma Independent Risk Factor for Tumor Progression in Low-Risk Bridge to Transplant Candidates

SIMPLE SUMMARY: With the increasing rates of early-stage hepatocellular carcinoma (HCC) diagnosis, patients are being diagnosed with less tumor burden and low biomarker levels. Assessing HCC prognosis in these patients is challenging as most prognosis strategies are based on elevated tumor burden and biomarkers. In this study we focus on albumin levels prior to HCC treatment based on the established roles of albumin in HCC incidence and overall survival outcomes. The role of albumin as a risk factor for HCC progression was investigated with the goal of demonstrating that albumin could identify optimal candidates for treatment in early-stage HCC. These results may also impact the field by identifying patients with advancing cirrhotic disease who require more aggressive approaches to HCC treatment. ABSTRACT: Due to active hepatocellular carcinoma (HCC) surveillance, many patients are diagnosed with early-stage disease and are usually amendable to curative treatments. These patients lack poor prognostic factors associated with Milan Criteria and alpha fetoprotein (AFP) biomarker levels. There are currently limited strategies to assess prognosis in the patients who remain at risk of post-treatment HCC progression. In a cohort of liver transplant (LT) candidates with HCC, this study seeks to identify factors prior to liver-directed therapy (LDT) associated with time to progression (TTP). This is a retrospective analysis of prospectively collected data from LT candidates with recently diagnosed HCC and receiving LDT as a bridge to LT at three interventional oncology programs within a single system (n = 373). Demographics, clinical hepatology and serology, and factors related to HCC burden were extracted and analyzed for associations with TTP risk. Albumin level below the cohort median (3.4 g/dL) emerged as an independent risk factor for TTP controlling for AFP > 20 ng/mL as well as Milan, T-stage, and Barcelona Clinic Liver Cancer (BCLC) stage individually. In modality-specific subgroup survival analysis, albumin-based TTP stratification was restricted to patients receiving first cycle microwave ablation (p = 0.007). In n = 162 patients matching all low-risk criteria for Milan, T-stage, BCLC stage, and AFP, the effect of albumin < 3.4 g/dL remained significant for TTP (p = 0.004) with 2-year TTP rates of 68% (<3.4 g/dL) compared to 95% (≥3.4 g/dL). In optimal bridge to LT candidates with small HCC and low AFP biomarker levels, albumin level at treatment baseline provides an HCC-independent positive prognostic factor for risk of HCC progression prior to LT.