AASLD guidelines for the treatment of hepatocellular carcinoma

Abstract

Potential conflict of interest: Laura M. Kulik is on the advisory board for Gilead, Bayer, Eisai, Salix, and Bristol‐Myers Squibb. Richard Finn consults for Pfizer, Bayer, Novartis, Merck, and Bristol‐Myers Squibb. Claude B. Sirlin consults for and has received grants from Virtualscopics. Lewis R. Roberts consults for Wako, Medscape, and Axis; advises Tavec and Bayer; is on the speakers' bureau for Onlive; and has received grants from Ariad, BTG, and Gilead. Andrew Zhu consults for Bristol‐Myers Squibb, Eisai, Merck, Novartis, Sanofi, and Bayer. The funding for the development of this Practice Guideline was provided by the American Association for the Study of Liver Diseases. Guiding Principles and Objectives GUIDING PRINCIPLES This document presents official recommendations of the American Association for the Study of Liver Diseases (AASLD) on the surveillance, diagnosis, and treatment of hepatocellular carcinoma (HCC) occurring in the setting of adults with cirrhosis. Unlike previous AASLD practice guidelines, the current guideline was developed in compliance with the Institute of Medicine standards for trustworthy practice guidelines and uses the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach.1 Multiple systematic reviews of the literature were conducted to support the recommendations in this practice guideline. An enhanced understanding of the guideline can be obtained by reading the applicable portions of the systematic reviews. In addition, more detailed information may be found in the associated guidance document related to clinically important aspects of HCC that lacked sufficient evidence to warrant a systematic review. The guideline focuses on a broad spectrum of clinical practice, including surveillance of patients with cirrhosis for HCC, establishing the diagnosis of HCC, and various therapeutic options for the treatment of HCC. To address other issues on HCC such as epidemiology, staging, and additional aspects of diagnosis and treatment, the authors have created a new guidance document that will be published soon and is based upon the previous HCC AASLD guidelines by Bruix and Sherman.2 KEY QUESTIONS The guideline developers from the AASLD identified key questions that health care providers are faced with frequently in the evaluation and management of patients with HCC. These questions were: Should adults with cirrhosis undergo surveillance for HCC? If so, which surveillance test is best? Should adults with cirrhosis and suspected HCC undergo diagnostic evaluation with multiphasic computed tomography (CT) or multiphasic magnetic resonance imaging (MRI)? Should adults with cirrhosis and an indeterminate hepatic nodule undergo a biopsy, repeated imaging, or alternative imaging for the diagnostic evaluation? Should adults with Child‐Pugh class A cirrhosis and early‐stage HCC (T1 or T2) be treated with resection or local‐regional (LRT) therapy? Should adults with cirrhosis and HCC that has been resected or ablated successfully undergo adjuvant therapy? Should adults with cirrhosis awaiting liver transplantation and HCC (T1) be treated or undergo observation? Should adults with cirrhosis and HCC (Organ Procurement and Transplantation Network [OPTN] T2) awaiting liver transplantation undergo transplantation alone or transplantation with bridging therapy while waiting? Should adults with cirrhosis awaiting liver transplantation and HCC beyond Milan criteria (T3) undergo transplantation after being down‐staged to within Milan criteria? Should adults with cirrhosis and HCC (T2 or T3, no vascular involvement) who are not candidates for resection or transplantation be treated with transarterial chemoembolization, transarterial radioembolization, or external radiation? Should adults with Child‐Pugh class A/B cirrhosis and advanced HCC with macrovascular invasion and/or metastatic disease be treated with systemic or locoregional therapies or no therapy? TARGET AUDIENCE This guideline is intended primarily for health care providers who care for patients with cirrhosis. Additionally, the guideline may inform policy decisions regarding patients with HCC. Background BURDEN OF DISEASE According to the World Health Organization, HCC is the fifth most common tumor worldwide and the second most common cause of cancer‐related death (http://globocan.iarc.fr/old/FactSheets/cancers/liver-new.asp). Male‐to‐female predominance is greater than 2:1 with liver cancer, and approximately 83% of the estimated 782,000 new HCC cases in 2012 occurred in less developed regions of the world, with East and South Asia plus sub‐Saharan Africa being the regions of highest incidence, Southern Europe and North America being the regions of intermediate incidence, and Northern Europe and South Central Asia being the regions of lowest incidence.3 The incidence of HCC has been rising rapidly in the United States over the last 20 years.4 According to estimates from the Surveillance Epidemiology End Results