High Rates of Treatment Stage Migration For Early Hepatocellular Carcinoma and Its Association With Adverse Impact On Outcomes: A Multicenter Study

Abstract Background & Aims:The rate of contraindications to percutaneous ablation (PA) for inoperable early HCC, and subsequent outcomes is not well described. We investigated the prevalence and outcomes of inoperable early HCC patients with contraindications to PA, resulting in treatment stage migration (TSM). Methods:BCLC 0/A patients diagnosed between September 2013 and September 2019 across five hospitals were identified. Primary endpoint was proportion of BCLC 0/A HCCs with contraindications to PA. Secondary endpoints included overall survival (OS), local tumour control (LTC) and recurrence-free survival (RFS). The causal effects of PA versus TSM were assessed using a potential outcome means (POM) framework in which the average treatment effects (ATE) of PA were estimated after accounting for potential selection bias and confounding.Results:245 patients with inoperable BCLC 0/A HCC were identified. 140 (57%) had contraindications to PA and received TSM therapy, 105 (43%) received PA. The main contraindication to PA was difficult tumour location (47%). Patients who received TSM therapy had lower median OS (2.1 versus 5.3years), LTC (1.0 versus 4.8years), and RFS (0.8 versus 2.7years); p<0.001 respectively, compared to PA. The ATE for PA versus TSM yielded an additional 1.02years (p=0.048), 2.87years (p<0.001) and 1.77years (p<0.001) for OS, LTC and RFS respectively. 3-year LTC after PA was suboptimal (63%).Conclusions:Our study highlights high rates of contraindication to PA in early HCCs, resulting in TSM and poorer outcomes. The local recurrence rate after PA was also high. Both findings support exploration of alternative ablative options for early HCCs.