Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clínic Barcelona, IDIBAPS, University of Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.
Background: Sorafenib improves overall survival (OS) of patients with hepatocellular carcinoma (HCC) in the absence of objective response. Thus, time to tumor progression (TTP) is used to capture benefits of novel molecular agents, but proof of its surrogacy with survival is lacking. Furthermore, survival predictors upon progression are not established and there is a need to characterize post-progression survival (PPS) and assess with time-dependent covariates analysis if it is influenced by progression pattern, and not solely by simultaneous impairment of liver function and performance status. Methods: We prospectively followed HCC patients treated with sorafenib. Clinical and biochemical evaluation were done every 4 weeks. Radiologic assessment of progression was done at week-4 and then, every 8 weeks using RECIST1.1. Progression pattern was divided into: intrahepatic/extrahepatic increase in tumor size, new intra-hepatic lesion, new extra-hepatic lesion (NEH). . Results: We included 147 patients (HCV57.1%, PS 0 83.6%, Child-Pugh A 82.3% and BCLC-C 47.3%). The median OS is 12.7 months and its independent predictors (HR [95%CI]) are: baseline BCLC 2.49[1.66-3.73], PS 1.86[1.12-3.10], registration during follow-up of Child-Pugh B or Child-Pugh C scores (2.36[1.51-3.69] and 2.89[1.62-5.15], respectively) definitive sorafenib interruption 2.48[1.54-4.01] and TTP 3.39[1.89-6.1]. Presence of NEH 2.42[1.32 - 4.44] is also an independent predictor of OS and PPS in patients with radiologic progression. Conclusion: Tumor progression is a surrogate of survival but its impact varies according to progression pattern. Thus, post-progression survival is influenced by progression pattern and this is key in prognostic prediction and second line trial design and analysis.