Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide and one of the leading causes of death among patients with cirrhosis. It has an increasing incidence in the United States because of the current epidemics of nonalcoholic fatty liver disease (NAFLD) and hepatitis C virus (HCV) cases.1 Prognosis for patients with HCC depends on tumor stage at diagnosis, with curative options only available for patients diagnosed at an early stage.2,3 Patients with early-stage HCC achieve 5-year survival rates near 70% with resection and transplantation, whereas those with advanced HCC have a median survival of less than 1 year.4,5
Surveillance using ultrasound at 6-month intervals is recommended in patients with cirrhosis.2,6,7 The goals of surveillance are to detect HCC at an early stage when it is amenable to curative therapy and to reduce all-cause mortality.8 Effective implementation of the screening process requires surveillance (obtaining an ultrasound in patients with cirrhosis), effective detection (finding HCC when it is present at an early stage), and appropriate follow-up (obtaining a 4-phase CT or MRI in patients with an abnormal ultrasound).9 Prior studies have suggested that HCC surveillance may be efficacious for detecting early HCC and improving survival; however, its effectiveness in clinical practice may be impacted by several factors, including low use rates and/or operator-dependency, leading to poor detection rates.10-15 Similarly, treatment underuse and delayed treatment may mitigate any survival benefit in patients who undergo surveillance and are found at an early stage.16,17
Despite improvements in technology and awareness, most HCC cases in the United States continue to be diagnosed at a late stage.18 This failure suggests potential breakdowns in the HCC screening process, including an absence of surveillance, failure of detection, or delayed follow-up. The purpose of this study was to characterize the impact of screening process failures on tumor stage at presentation and overall survival in clinical practice among a racially diverse cohort of patients.
See page 381 for authorship statement.
This work was conducted with support from Center for Translational Medicine, NIH/NCATS Grant Number KL2 TR000453 and the ACG Junior Faculty Development Award awarded to Dr. Singal. The content is solely the responsibility of the authors and does not necessarily represent the official views of Center for Translational Medicine, the University of Texas Southwestern Medical Center and its affiliated academic and health care centers, the National Center for Advancing Translational Sciences, or the National Institutes of Health. The authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.
El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 2007;132:2557–2576.
Padhya KT, Marrero JA, Singal AG. Recent advances in the treatment of hepatocellular carcinoma. Curr Opin Gastroenterol 2013;29:285–292.
Llovet JM, Bustamante J, Castells A. Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials. Hepatology 1999;29:62–67.
Mazzaferro V, Regalia E, Doci R. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996;334:693–699.
Bruix J, Sherman M, Llovet JM. Clinical management of hepatocellular carcinoma: conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 2001;35:421–430.
Lin OS, Keeffe EB, Sanders GD, Owens DK. Cost-effectiveness of screening for hepatocellular carcinoma in patients with cirrhosis due to chronic hepatitis C. Aliment Pharmacol Ther 2004;19:1159–1172.
Singal AG, Pillai A, Tiro JA. Early detection, curative treatment, and survival rates for HCC surveillance in patients with cirrhosis: a meta-analysis. PLOS Medicine 2014; in press.
Zapka JG, Taplin SH, Solberg LI, Manos MM. A framework for improving the quality of cancer care: the case of breast and cervical cancer screening. Cancer Epidemiol Biomarkers Prev 2003;12:4–13.
Davila JA, Henderson L, Kramer JR. Utilization of surveillance for hepatocellular carcinoma among hepatitis C virus-infected veterans in the United States. Ann Intern Med 2011;154:85–93.
Davila JA, Morgan RO, Richardson PA. Use of surveillance for hepatocellular carcinoma among patients with cirrhosis in the United States. Hepatology 2010;52:132–141.
Singal A, Volk ML, Waljee A. Meta-analysis: surveillance with ultrasound for early-stage hepatocellular carcinoma in patients with cirrhosis. Aliment Pharmacol Ther 2009;30:37–47.
Singal AG, Conjeevaram HS, Volk ML. Effectiveness of hepatocellular carcinoma surveillance in patients with cirrhosis. Cancer Epidemiol Biomarkers Prev 2012;21:793–799.
Singal AG, Nehra M, Adams-Huet B. Detection of hepatocellular carcinoma at advanced stages among patients in the HALT-C trial: where did surveillance fail? Am J Gastroenterol 2013;108:425–432.
Singal AG, Tiro JA, Gupta S. Improving hepatocellular carcinoma screening: applying lessons from colorectal cancer screening. Clin Gastroenterol Hepatol 2013;11:472–477.
Singal AG, Waljee AK, Patel N. Therapeutic delays lead to worse survival among patients with hepatocellular carcinoma. J Natl Compr Canc Netw 2013;11:1101–1108.
Tan D, Yopp A, Beg MS. Meta-analysis: underutilisation and disparities of treatment among patients with hepatocellular carcinoma in the United States. Aliment Pharmacol Ther 2013;38:703–712.
Altekruse SF, McGlynn KA, Dickie LA, Kleiner DE. Hepatocellular carcinoma confirmation, treatment, and survival in surveillance, epidemiology, and end results registries, 1992-2008. Hepatology 2012;55:476–482.
Barbara L, Benzi G, Gaiani S. Natural history of small untreated hepatocellular carcinoma in cirrhosis: a multivariate analysis of prognostic factors of tumor growth rate and patient survival. Hepatology 1992;16:132–137.
Kubota K, Ina H, Okada Y, Irie T. Growth rate of primary single hepatocellular carcinoma: determining optimal screening interval with contrast enhanced computed tomography. Dig Dis Sci 2003;48:581–586.
Singal AG, Yopp A, Skinner CS. Utilization of hepatocellular carcinoma surveillance among American patients: a systematic review. J Gen Intern Med 2012;27:861–867.
Singal A, Volk M, Rakoski M. Patient involvement is correlated with higher HCC surveillance in patients with cirrhosis. J Clin Gastroenterol 2011;45:727–732.
Singal AG, Yopp AC, Gupta S. Failure rates in the hepatocellular carcinoma surveillance process. Cancer Prev Res (Phila) 2012;5:1124–1130.
Stravitz RT, Heuman DM, Chand N. Surveillance for hepatocellular carcinoma in patients with cirrhosis improves outcome. Am J Med 2008;121:119–126.
Trinchet JC, Chaffaut C, Bourcier V. Ultrasonographic surveillance of hepatocellular carcinoma in cirrhosis: a randomized trial comparing 3- and 6-month periodicities. Hepatology 2011;54:1987–1997.