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• W2000156013 abstract "Hepatocellular carcinoma is a leading cause of death in patients with cirrhosis. Management algorithms continually are increasing in sophistication and involve application of single and multimodality treatments, including liver transplantation, hepatic resection, ablation, transarterial chemoembolization, radioembolization, and systemic chemotherapy. These treatments have been shown to increase survival times. As many as 75% of patients with limited-stage disease who are given curative therapies survive 5 years, whereas less than 20% of untreated patients survive 1 year. Treatment can be optimized based on the patient's tumor stage, hepatic reserve, and functional status. However, because of the heterogeneity in presentation among patients, a multidisciplinary approach is required to treat hepatocellular carcinoma, involving hepatologists, surgeons, interventional radiologists, and oncologists. We present each specialist's viewpoint on controversies and advances in the management of hepatocellular carcinoma. Hepatocellular carcinoma is a leading cause of death in patients with cirrhosis. Management algorithms continually are increasing in sophistication and involve application of single and multimodality treatments, including liver transplantation, hepatic resection, ablation, transarterial chemoembolization, radioembolization, and systemic chemotherapy. These treatments have been shown to increase survival times. As many as 75% of patients with limited-stage disease who are given curative therapies survive 5 years, whereas less than 20% of untreated patients survive 1 year. Treatment can be optimized based on the patient's tumor stage, hepatic reserve, and functional status. However, because of the heterogeneity in presentation among patients, a multidisciplinary approach is required to treat hepatocellular carcinoma, involving hepatologists, surgeons, interventional radiologists, and oncologists. We present each specialist's viewpoint on controversies and advances in the management of hepatocellular carcinoma. The incidence of hepatocellular carcinoma (HCC), a common complication of cirrhosis, continues to increase in the United States.1El-Serag H.B. Marrero J.A. Rudolph L. et al.Diagnosis and treatment of hepatocellular carcinoma.Gastroenterology. 2008; 134: 1752-1763Abstract Full Text Full Text PDF PubMed Scopus (883) Google Scholar The number of hospitalizations and economic burden attributable to HCC are substantial.2Kim W.R. Gores G.J. Benson J.T. et al.Mortality and hospital utilization for hepatocellular carcinoma in the United States.Gastroenterology. 2005; 129: 486-493Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar, 3Lang K. Danchenko N. Gondek K. et al.The burden of illness associated with hepatocellular carcinoma in the United States.J Hepatol. 2009; 50: 89-99Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar The 1-year survival rate for untreated HCC is less than 20%, but improves to more than 75% for patients with limited-stage disease who undergo curative treatments.4Cabibbo G. Enea M. Attanasio M. et al.A meta-analysis of survival rates of untreated patients in randomized clinical trials of hepatocellular carcinoma.Hepatology. 2010; 51: 1274-1283Crossref PubMed Scopus (317) Google Scholar, 5Pelletier S.J. Fu S. Thyagarajan V. et al.An intention-to-treat analysis of liver transplantation for hepatocellular carcinoma using organ procurement transplant network data.Liver Transplant. 2009; 15: 859-868Crossref PubMed Scopus (116) Google Scholar Only 30% of patients with HCC present with limited-stage disease, and data indicate underuse of curative and palliative therapies for these patients.6Wong R.J. Corley D.A. Survival differences by race/ethnicity and treatment for localized hepatocellular carcinoma within the United States.Dig Dis Sci. 2009; 54: 2031-2039Crossref PubMed Scopus (38) Google Scholar, 7El-Serag H.B. Siegel A.B. Davila J.A. et al.Treatment and outcomes of treating hepatocellular carcinoma among Medicare recipients in the United States: a population-based study.J Hepatol. 2006; 44: 158-166Abstract Full Text Full Text PDF PubMed Scopus (210) Google Scholar The risk of HCC recurrence is an important consideration that influences choice of HCC therapy and surveillance strategies.8Llovet J.M. Schwartz M. Mazzaferro V. Resection and liver transplantation for hepatocellular carcinoma.Semin Liver Dis. 2005; 25: 181-200Crossref PubMed Scopus (740) Google ScholarOptions available to treat HCC have become increasingly complex; a multidisciplinary approach to patient care is required by a team of providers with complementary expertise and skill sets that includes hepatologists, radiologists, interventional radiologists, surgeons, and oncologists. Available therapies, used alone or in combination, include liver transplantation (LT); hepatic resection; liver-directed therapies such as ablation (alcohol, microwave, and radiofrequency), transarterial chemoembolization (TACE), radioembolization, and conformal or stereotactic radiation; and systemic chemotherapy with sorafenib and investigational agents. The type of treatment most appropriate for an individual patient with HCC is based on tumor stage, hepatic reserve, and functional status.Multiple cancer-staging systems have been proposed.9Pons F. Varela M. Llovet J.M. Staging systems in hepatocellular carcinoma.HPB (Oxford). 2005; 7: 35-41Abstract Full Text Full Text PDF PubMed Scopus (191) Google Scholar The Barcelona Clinic Liver Cancer (BCLC) staging system (Figure 1) is the only one that links treatment and prognosis with cancer stage, degree of liver dysfunction as assessed by the Child–Pugh scoring system, and patient functional status; use of the BCLC therefore is advocated by the American Association for the Study of Liver Disease guideline on HCC management.10Llovet J.M. Brú C. Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification.Semin Liver Dis. 1999; 19: 329-338Crossref PubMed Scopus (2877) Google Scholar, 11Bruix J. Sherman M. American Association for the Study of Liver DiseasesManagement of hepatocellular carcinoma: an update.Hepatology. 2011; 53: 1020-1022Crossref PubMed Scopus (6512) Google Scholar Multimodal treatments that use combination therapies are not outlined within the BCLC schema but often are used in clinical practice, with good effects.12Cabibbo G. Latteri F. Antonucci M. et al.Multimodal approaches to the treatment of hepatocellular carcinoma.Nat Clin Pract Gastroenterol Hepatol. 2009; 6: 159-169Crossref PubMed Scopus (67) Google Scholar A multidisciplinary approach is required to manage patients with HCC because of the heterogeneity in presentation, variation among patients who are candidates for recommended treatments, and diversity of responses to therapy in clinical practice. We present perspectives from hepatology, surgery, interventional radiology, and oncology specialties on the controversies and advances in HCC management.Very Early Stage DiseaseVery early stage HCC is defined by a BCLC stage of 0, a single tumor of less than 2 cm in size, normal functional status, and preserved hepatic function (Child–Pugh class A).The diagnosis of HCC is covered in-depth in the American Association for the Study of Liver Disease guideline for HCC management and will not be discussed here.11Bruix J. Sherman M. American Association for the Study of Liver DiseasesManagement of hepatocellular carcinoma: an update.Hepatology. 2011; 53: 1020-1022Crossref PubMed Scopus (6512) Google Scholar Patients with a single HCC lesion that is less than 2 cm have tumors of the T1 stage, according to the modified American Joint Committee on Cancer (AJCC)-TNM staging system, and therefore are not eligible for HCC model for end-stage liver disease (MELD) exception points for LT in the United States.13Vauthey J.N. Lauwers G.Y. Esnaola N.F. et al.Simplified staging for hepatocellular carcinoma.J Clin Oncol. 2002; 20: 1527-1536Crossref PubMed Scopus (588) Google Scholar There is controversy about whether these patients should receive immediate therapy for HCC or be monitored until they meet T2 criteria, when they can be considered for LT with HCC exception status. In patients with very early stage disease, hepatic resection or ablation offers equivalent treatment response and survival rates; however, disease recurrence remains high within 5 years.14Takayama T. Makuuchi M. Hirohashi S. et al.Early hepatocellular carcinoma as an entity with a high rate of surgical cure.Hepatology. 1998; 28: 1241-1246Crossref PubMed Scopus (354) Google Scholar, 15Ikai I. Arii S. Kojiro M. et al.Reevaluation of prognostic factors for survival after liver resection in patients with hepatocellular carcinoma in a Japanese nationwide survey.Cancer. 2004; 101: 796-802Crossref PubMed Scopus (368) Google Scholar, 16Zhou X.D. Tang Z.Y. Yang B.H. et al.Experience of 1000 patients who underwent hepatectomy for small hepatocellular carcinoma.Cancer. 2001; 91: 1479-1486Crossref PubMed Scopus (254) Google Scholar, 17Nathan H. Schulick R.D. Choti M.A. et al.Predictors of survival after resection of early hepatocellular carcinoma.Ann Surg. 2009; 249: 799-805Crossref PubMed Scopus (217) Google Scholar, 18Livraghi T. Meloni F. Di Stasi M. et al.Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: is resection still the treatment of choice?.Hepatology. 2008; 47: 82-89Crossref PubMed Scopus (866) Google Scholar, 19Rhim H. Lim H.K. Choi D. Current status of radiofrequency ablation of hepatocellular carcinoma.World J Gastrointest Surg. 2010; 2: 128-136Crossref PubMed Google Scholar, 20Sala M. Llovet J.M. Vilana R. et al.Initial response to percutaneous ablation predicts survival in patients with hepatocellular carcinoma.Hepatology. 2004; 40: 1352-1360Crossref PubMed Scopus (383) Google ScholarSurgical PerspectiveHepatic resection or ablation of HCC lesions less than 2 cm have the same 5-year survival rates.14Takayama T. Makuuchi M. Hirohashi S. et al.Early hepatocellular carcinoma as an entity with a high rate of surgical cure.Hepatology. 1998; 28: 1241-1246Crossref PubMed Scopus (354) Google Scholar, 15Ikai I. Arii S. Kojiro M. et al.Reevaluation of prognostic factors for survival after liver resection in patients with hepatocellular carcinoma in a Japanese nationwide survey.Cancer. 2004; 101: 796-802Crossref PubMed Scopus (368) Google Scholar, 16Zhou X.D. Tang Z.Y. Yang B.H. et al.Experience of 1000 patients who underwent hepatectomy for small hepatocellular carcinoma.Cancer. 2001; 91: 1479-1486Crossref PubMed Scopus (254) Google Scholar, 17Nathan H. Schulick R.D. Choti M.A. et al.Predictors of survival after resection of early hepatocellular carcinoma.Ann Surg. 2009; 249: 799-805Crossref PubMed Scopus (217) Google Scholar, 18Livraghi T. Meloni F. Di Stasi M. et al.Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: is resection still the treatment of choice?.Hepatology. 2008; 47: 82-89Crossref PubMed Scopus (866) Google Scholar, 19Rhim H. Lim H.K. Choi D. Current status of radiofrequency ablation of hepatocellular carcinoma.World J Gastrointest Surg. 2010; 2: 128-136Crossref PubMed Google Scholar, 20Sala M. Llovet J.M. Vilana R. et al.Initial response to percutaneous ablation predicts survival in patients with hepatocellular carcinoma.Hepatology. 2004; 40: 1352-1360Crossref PubMed Scopus (383) Google Scholar The type of therapy chosen is determined based on tumor location, hepatic function, functional status, other comorbidities, and local patterns of practice. Resection should be limited to patients with compensated cirrhosis (defined by a bilirubin level of <2 mg/dL, the absence of portal hypertension, and more than 100,000 platelets/mL).21Llovet J.M. Fuster J. Bruix J. Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation.Hepatology. 1999; 30: 1434-1440Crossref PubMed Scopus (1471) Google Scholar In studies of cirrhotic patients with Child–Pugh class A disease who underwent resection for HCC (including patients with lesions <2 cm), the 5-year survival rates ranged from 49% to 93%; 5-year recurrence rates were as high as 80%.14Takayama T. Makuuchi M. Hirohashi S. et al.Early hepatocellular carcinoma as an entity with a high rate of surgical cure.Hepatology. 1998; 28: 1241-1246Crossref PubMed Scopus (354) Google Scholar, 15Ikai I. Arii S. Kojiro M. et al.Reevaluation of prognostic factors for survival after liver resection in patients with hepatocellular carcinoma in a Japanese nationwide survey.Cancer. 2004; 101: 796-802Crossref PubMed Scopus (368) Google Scholar, 16Zhou X.D. Tang Z.Y. Yang B.H. et al.Experience of 1000 patients who underwent hepatectomy for small hepatocellular carcinoma.Cancer. 2001; 91: 1479-1486Crossref PubMed Scopus (254) Google Scholar, 17Nathan H. Schulick R.D. Choti M.A. et al.Predictors of survival after resection of early hepatocellular carcinoma.Ann Surg. 2009; 249: 799-805Crossref PubMed Scopus (217) Google ScholarAlthough multiple studies have evaluated the effects of ablation of tumors of 3 cm or larger, only a few studies specifically have evaluated ablation of HCC lesions less than 2 cm.18Livraghi T. Meloni F. Di Stasi M. et al.Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: is resection still the treatment of choice?.Hepatology. 2008; 47: 82-89Crossref PubMed Scopus (866) Google Scholar, 19Rhim H. Lim H.K. Choi D. Current status of radiofrequency ablation of hepatocellular carcinoma.World J Gastrointest Surg. 2010; 2: 128-136Crossref PubMed Google Scholar, 20Sala M. Llovet J.M. Vilana R. et al.Initial response to percutaneous ablation predicts survival in patients with hepatocellular carcinoma.Hepatology. 2004; 40: 1352-1360Crossref PubMed Scopus (383) Google Scholar In a prospective cohort study of 218 patients of Child–Pugh class A who received radiofrequency ablation (RFA) for lesions that were 2 cm or less, 97% had a complete response over a median 31-month follow-up period.18Livraghi T. Meloni F. Di Stasi M. et al.Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: is resection still the treatment of choice?.Hepatology. 2008; 47: 82-89Crossref PubMed Scopus (866) Google Scholar The overall 5-year rate of survival was 69% and the complication rate was 1.8%. Although the rate of local recurrence was low, the estimated overall 5-year rate of recurrence was as high as 80%. There has been no randomized controlled trial (RCT) to compare resection with RFA specifically in patients with lesions less than 2 cm, probably because the sample size and length of follow-up evaluation required to perform such a study are prohibitive. A Markov model simulating 10,000 patients with compensated cirrhosis and HCC smaller than 2 cm who are treated by percutaneous RFA, resection, or percutaneous RFA, followed by resection among those who do not respond, estimates the overall survival times for each approach to be more than 7 years.22Cho Y.K. Kim J.K. Kim W.T. et al.Hepatic resection versus radiofrequency ablation for very early stage hepatocellular carcinoma: a Markov model analysis.Hepatology. 2010; 51: 1284-1290Crossref PubMed Scopus (180) Google ScholarInterventional Radiology PerspectiveOf the ablative techniques, RFA is better for patients with very early or early stage HCC than percutaneous ethanol ablation or microwave catheter ablation. A meta-analysis of 4 RCTs that included studies of patients with lesions larger than 2 cm found that RFA had better 3-year survival rates than percutaneous ethanol ablation (63%–91% vs 48%–61%).23Cho Y.K. Kim J.K. Kim M.Y. et al.Systematic review of randomized trials for hepatocellular carcinoma treated with percutaneous ablation therapies.Hepatology. 2009; 49: 453-459Crossref PubMed Scopus (366) Google Scholar Percutaneous ethanol ablation and RFA resulted in equivalent survival times for patients with lesions smaller than 2 cm, although RFA requires fewer treatment sessions and has a more predictable response. There has been no RCT to compare RFA and TACE for potentially resectable HCC, including lesions smaller than 2 cm. In a small study of 40 patients with unresectable small HCC (median size, <3 cm), 80% of patients who received either TACE or RFA survived 1 year.24Chok K.S. Ng K.K. Poon R.T. et al.Comparable survival in patients with unresectable hepatocellular carcinoma treated by radiofrequency ablation or transarterial chemoembolization.Arch Surg. 2006; 141: 1231-1236Crossref PubMed Scopus (25) Google Scholar Although no single RCT has shown that combination therapy with TACE and RFA increases survival times of patients with very early stage disease, compared with either therapy alone, a meta-analysis of 4 RCTs reported that combination therapy did increase survival time, regardless of tumor size.25Shibata T. Isoda H. Hirokawa Y. et al.Small hepatocellular carcinoma: is radiofrequency ablation combined with transcatheter arterial chemoembolization more effective than radiofrequency ablation alone for treatment?.Radiology. 2009; 252: 905-913Crossref PubMed Scopus (189) Google Scholar, 26Marelli L. Stigliano R. Triantos C. et al.Treatment outcomes for hepatocellular carcinoma using chemoembolization in combination with other therapies.Cancer Treat Rev. 2006; 32: 594-606Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar TACE should not be used alone as first-line therapy in patients who can be treated with ablation or resection.Hepatology PerspectiveThere is controversy over the optimal management strategy for compensated cirrhotic patients with a single HCC that is smaller than 2 cm. HCCs smaller than 2 cm are classified as T1 by modified AJCC–TNM staging and therefore are not eligible to receive MELD HCC exception points for LT listings in the United States. A Markov model of cirrhotic patients of Child–Pugh class A, with a single lesion smaller than 2 cm, found that immediate treatment with RFA or TACE had equivalent survival times, and was more cost effective, than waiting until the lesion was larger than 2 cm so the patient could be placed on the LT wait list with HCC exception status.27Naugler W.E. Sonnenberg A. Survival and cost-effectiveness analysis of competing strategies in the management of small hepatocellular carcinoma.Liver Transplant. 2010; 16: 1186-1194Crossref PubMed Scopus (45) Google Scholar However, this model did not include important factors such as hepatic decompensation or the development of recurrent or new tumors. A recent study of 159 patients with tumors smaller than 2 cm found that 56% developed recurrent HCC after RFA during a median follow-up period of 29 months, and that 18% of these had advanced-stage tumors.28Rossi S. Ravetta V. Rosa L. et al.Repeated radiofrequency ablation for management of patients with cirrhosis with small hepatocellular carcinomas: a long-term cohort study.Hepatology. 2011; 53: 136-147Crossref PubMed Scopus (137) Google Scholar Geographic differences in wait times, which vary by United Network for Organ Sharing (UNOS) region, are another important factor to consider in determining whether to chose LT for patients with very early stage disease29Freeman R.B. Edwards E.B. Harper A.M. Waiting list removal rates among patients with chronic and malignant liver diseases.Am J Transplant. 2006; 6: 1416-1421Crossref PubMed Scopus (180) Google Scholar, 30Roberts J.P. Venook A. Kerlan R. et al.Hepatocellular carcinoma: ablate and wait versus rapid transplantation.Liver Transplant. 2010; 16: 925-929Crossref PubMed Scopus (108) Google Scholar (Figure 2). Further data are needed to better characterize the risk:benefit ratio of early versus late HCC treatment in this group of patients.Figure 2Percentage of patients undergoing liver transplantation within 3 months of listing by UNOS region in 2007.30Roberts J.P. Venook A. Kerlan R. et al.Hepatocellular carcinoma: ablate and wait versus rapid transplantation.Liver Transplant. 2010; 16: 925-929Crossref PubMed Scopus (108) Google ScholarView Large Image Figure ViewerDownload Hi-res image Download (PPT)Patients who receive resection or ablation therapy should be monitored closely for HCC recurrence and signs of decompensation. There are not much data to define an optimal surveillance protocol after treatment, but multiphase, cross-sectional image analysis 1 month after treatment, and then at 3-month intervals, has been proposed for at least the first 2 years after treatment, with possibly longer intervals (up to 6 mo) thereafter.11Bruix J. Sherman M. American Association for the Study of Liver DiseasesManagement of hepatocellular carcinoma: an update.Hepatology. 2011; 53: 1020-1022Crossref PubMed Scopus (6512) Google Scholar Hepatologists also must treat underlying liver diseases; patients with hepatitis B who receive antiviral therapies have been shown to have decreased rates of cirrhosis, decompensation, and HCC.31Liaw Y.F. Sung J.J. Chow W.C. et al.Lamivudine for patients with chronic hepatitis B and advanced liver disease.N Engl J Med. 2004; 351: 1521-1531Crossref PubMed Scopus (1972) Google Scholar The efficacy of interferon therapy in reducing HCC recurrence after resection in patients with hepatitis C is controversial.32Singal A.K. Freeman Jr, D.H. Anand B.S. Meta-analysis: interferon improves outcomes following ablation or resection of hepatocellular carcinoma.Aliment Pharmacol Ther. 2010; 32: 851-858Crossref PubMed Scopus (101) Google Scholar, 33Mazzaferro V. Romito R. Schiavo M. et al.Prevention of hepatocellular carcinoma recurrence with alpha-interferon after liver resection in HCV cirrhosis.Hepatology. 2006; 44: 1543-1554Crossref PubMed Scopus (316) Google ScholarEarly Stage DiseasePatients with early stage disease are assigned BCLC stage A and have a single lesion or up to 3 lesions, none greater than 3 cm in size, no evidence of extrahepatic spread of disease or vascular invasion, normal performance status, and are of Child–Pugh classes A or B.These patients have tumors of the T2 stage, based on the modified AJCC-TNM staging system, and also are within Milan criteria if the single lesion is not greater than 5 cm in size. In management of these patients, there are controversies over the relative risks and benefits of LT to candidates eligible for resection, the role of salvage transplantation in patients previously treated with resection, whether ablation is equivalent to resection of lesions that are 3 to 5 cm, and the use of liver-directed therapies in patients awaiting LT.Surgical PerspectiveFirst-line therapy for patients with Child–Pugh class A cirrhosis but no portal hypertension and a single HCC lesion traditionally has been hepatic resection.11Bruix J. Sherman M. American Association for the Study of Liver DiseasesManagement of hepatocellular carcinoma: an update.Hepatology. 2011; 53: 1020-1022Crossref PubMed Scopus (6512) Google ScholarFifty percent to 75% of cirrhotic patients with a single lesion and no portal hypertension, but less than 55% in those with portal hypertension or multiple or large lesions, survive for 5 years.15Ikai I. Arii S. Kojiro M. et al.Reevaluation of prognostic factors for survival after liver resection in patients with hepatocellular carcinoma in a Japanese nationwide survey.Cancer. 2004; 101: 796-802Crossref PubMed Scopus (368) Google Scholar, 16Zhou X.D. Tang Z.Y. Yang B.H. et al.Experience of 1000 patients who underwent hepatectomy for small hepatocellular carcinoma.Cancer. 2001; 91: 1479-1486Crossref PubMed Scopus (254) Google Scholar, 34Ishizawa T. Hasegawa K. Aoki T. et al.Neither multiple tumors nor portal hypertension are surgical contraindications for hepatocellular carcinoma.Gastroenterology. 2008; 134: 1908-1916Abstract Full Text Full Text PDF PubMed Scopus (537) Google Scholar, 35Poon R.T. Liver transplantation for solitary hepatocellular carcinoma less than 3 cm in diameter in Child A cirrhosis.Dig Dis. 2007; 25: 334-340Crossref PubMed Scopus (7) Google Scholar HCC recurs within 5 years in up to 80% of patients treated by resection.15Ikai I. Arii S. Kojiro M. et al.Reevaluation of prognostic factors for survival after liver resection in patients with hepatocellular carcinoma in a Japanese nationwide survey.Cancer. 2004; 101: 796-802Crossref PubMed Scopus (368) Google Scholar, 36Koike Y. Shiratori Y. Sato S. et al.Risk factors for recurring hepatocellular carcinoma differ according to infected hepatitis virus—an analysis of 236 consecutive patients with a single lesion.Hepatology. 2000; 32: 1216-1223Crossref PubMed Scopus (125) Google Scholar Factors that increase the risk of recurrence include larger size and number of HCC lesions, higher histologic tumor grade, higher levels of α-fetoprotein, and macrovascular and microvascular invasion.15Ikai I. Arii S. Kojiro M. et al.Reevaluation of prognostic factors for survival after liver resection in patients with hepatocellular carcinoma in a Japanese nationwide survey.Cancer. 2004; 101: 796-802Crossref PubMed Scopus (368) Google Scholar, 37Pawlik T.M. Delman K.A. Vauthey J.N. et al.Tumor size predicts vascular invasion and histologic grade: implications for selection of surgical treatment for hepatocellular carcinoma.Liver Transplant. 2005; 11: 1086-1092Crossref PubMed Scopus (491) Google Scholar, 38Roayaie S. Blume I.N. Thung S.N. et al.A system of classifying microvascular invasion to predict outcome after resection in patients with hepatocellular carcinoma.Gastroenterology. 2009; 137: 850-855Abstract Full Text Full Text PDF PubMed Scopus (404) Google Scholar Adjuvant therapies have not been shown to reduce recurrence; however, a multicenter, placebo-controlled trial is underway to determine whether sorafenib reduces the recurrence of HCC after resection (NCT00692770, available at: www.clinicaltrials.gov). Gene expression signatures associated with high or low probabilities of recurrence have been identified and may have future clinical application in predicting the relative benefits of various therapies for an individual patient.39Hoshida Y. Villanueva A. Kobayashi M. et al.Gene expression in fixed tissues and outcome in hepatocellular carcinoma.N Engl J Med. 2008; 359: 1995-2004Crossref PubMed Scopus (1018) Google Scholar, 40Villanueva A. Hoshida Y. Battiston C. et al.Combining clinical, pathology, and gene expression data to predict recurrence of hepatocellular carcinoma.Gastroenterology. 2011; 140: 1501-1512Abstract Full Text Full Text PDF PubMed Scopus (320) Google ScholarIt is not clear if patients with HCC lesions 3 to 5 cm have comparable outcomes after ablation or resection. In an RCT conducted in China of 186 Child–Pugh class A patients, with HCCs that were less than 5 cm, there were no statistically significant differences in rates of 4-year overall and disease-free survival between patients treated with resection (64% and 52%, respectively) versus RFA (66% and 48%, respectively).41Chen M.S. Li J.Q. Zheng Y. et al.A prospective randomized trial comparing percutaneous local ablative therapy and partial hepatectomy for small hepatocellular carcinoma.Ann Surg. 2006; 243: 321-328Crossref PubMed Scopus (1140) Google Scholar Observational studies have reported variable results with RFA versus resection, with outcomes dependent on tumor size.20Sala M. Llovet J.M. Vilana R. et al.Initial response to percutaneous ablation predicts survival in patients with hepatocellular carcinoma.Hepatology. 2004; 40: 1352-1360Crossref PubMed Scopus (383) Google Scholar, 42Lencioni R. Cioni D. Crocetti L. et al.Early-stage hepatocellular carcinoma in patients with cirrhosis: long-term results of percutaneous image-guided radiofrequency ablation.Radiology. 2005; 234: 961-967Crossref PubMed Scopus (701) Google Scholar, 43N'Kontchou G. Mahamoudi A. Aout M. et al.Radiofrequency ablation of hepatocellular carcinoma: long-term results and prognostic factors in 235 Western patients with cirrhosis.Hepatology. 2009; 50: 1475-1483Crossref PubMed Scopus (347) Google Scholar, 44Santambrogio R. Opocher E. Zuin M. et al.Surgical resection versus laparoscopic radiofrequency ablation in patients with hepatocellular carcinoma and Child-Pugh class A liver cirrhosis.Ann Surg Oncol. 2009; 16: 3289-3298Crossref PubMed Scopus (55) Google Scholar The response to RFA is 70% to 95% among patients with lesions less than 3 cm, but decreases to approximately 50% in patients with lesions greater than 3 cm.20Sala M. Llovet J.M. Vilana R. et al.Initial response to percutaneous ablation predicts survival in patients with hepatocellular carcinoma.Hepatology. 2004; 40: 1352-1360Crossref PubMed Scopus (383) Google Scholar Among patients with lesions more than 3 cm who were treated with RFA, the overall 5-year survival rate was 30% to 50% and the 5-year recurrence rate reached 80%.42Lencioni R. Cioni D. Crocetti L. et al.Early-stage hepatocellular carcinoma in patients with cirrhosis: long-term results of percutaneous image-guided radiofrequency ablation.Radiology. 2005; 234: 961-967Crossref PubMed Scopus (701) Google Scholar, 43N'Kontchou G. Mahamoudi A. Aout M. et al.Radiofrequency ablation of hepatocellular carcinoma: long-term results and prognostic factors in 235 Western patients with cirrhosis.Hepatology. 2009; 50: 1475-1483Crossref PubMed Scopus (347) Google Scholar, 44Santambrogio R. Opocher E. Zuin M. et al.Surgical resection versus laparoscopic radiofrequency ablation in patients with hepatocellular carcino" @default.
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• W2000156013 title "Multidisciplinary Management of Hepatocellular Carcinoma" @default.
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• W2000156013 doi "https://doi.org/10.1016/j.cgh.2011.11.008" @default.
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