Stage 0, A, and B Adult Primary Liver Cancer
Localized hepatocellular carcinomas (HCCs) that present either as a solitary mass in a portion of the liver or as a limited number of tumors (three nodules, each <3 cm in diameter) without major vascular invasion constitute approximately 30% of the HCC cases. The three potentially curative therapies (i.e., liver transplantation, surgical resection, and ablation techniques) are acceptable treatment options for small, single-nodule HCC in patients with well-preserved liver function. Surgery is the mainstay of HCC treatment. Resection and transplantation achieve the best outcomes in well-selected candidates and are usually considered to be the first option for curative intent.
Liver transplantation is a potentially curative therapy for HCC and has the benefit of treating the underlying cirrhosis, but the scarcity of organ donors limits the availability of this treatment modality.
Liver transplantation is determined by the Milan criteria, which is defined as a single HCC lesion smaller than 5 cm, or 2 to 3 nodules smaller than 3 cm. Expansion of the accepted transplantation for HCC is not supported by consistent data. Liver transplantation is considered if resection is precluded as a result of multiple, small, tumor nodules (≤3 nodules, each <3 cm), or if the liver function is impaired (Child-Pugh B and C class). In those patients, transplantation is associated with a 5-year overall survival (OS) rate of approximately 70%.[Level of evidence: 3iii]
Surgical resection can be considered for patients who present with the following:
- A solitary mass.
- Good performance status.
- Normal or minimally abnormal liver function tests.
- No evidence of portal hypertension.
- No evidence of cirrhosis beyond Child-Pugh class A.
The principles of surgical resection involve obtaining a clear margin around a tumor, which may require any of the following:
- Segmental resection.
- Hormone-lymphatic lobectomy.
- Extended lobectomy.
Hepatic resection is controversial in patients with limited multifocal disease.
Preoperative assessment includes three-phase helical computed tomography, magnetic resonance imaging, or both to determine the presence of an extension of a tumor across interlobar planes and potential involvement of the hepatic hilus, hepatic veins, and inferior vena cava. Tumors can be resected only if a sufficient amount of liver parenchyma can be spared with adequate vascular and biliary inflow and outflow. Patients with well-compensated cirrhosis can generally tolerate resection of up to 50% of their liver parenchyma. After considering the location and number of tumors, and the patient's hepatic function, only 5% to 10% of liver cancer patients will prove to have localized disease amenable to resection. The 5-year OS rates following curative resection range between 27% and 70% and depend on tumor stage and underlying liver function.[1,3-6]
When tumor excision, either by transplant or resection, is not feasible or advisable, ablation techniques may be used if the tumor can be accessed percutaneously or, if necessary, through minimally invasive or open surgery. Ablation can be achieved in the following ways:
- Through exposure to a chemical substance (e.g., ethanol).
- Through changes in temperatures (e.g., radiofrequency ablation [RFA], microwave, or cryoablation).
- By direct damage of the cellular membrane (definitive electroporation).
Ablation may be particularly useful for patients with early HCC that is centrally located in the liver and cannot be surgically removed without excessive sacrifice of functional parenchyma.
Ablation should include a margin of normal liver around the tumor. Ablation is relatively contraindicated for lesions in close proximity to bile ducts, the diaphragm, or other intra-abdominal organs that might be injured during the ablation. Furthermore, when tumors are located adjacent to major vessels, the blood flow in the vessels may decrease the temperature reached when thermal ablation techniques such as RFA are used. This is known as the heat sink effect, which may preclude a complete tumor necrosis.
Percutaneous ethanol injection (PEI) obtains good results in patients with Child-Pugh class A cirrhosis and a single tumor less than 3 cm in diameter. In those cases, the 5-year OS rate is expected to be as high as 40% to 59%.[7,8][Level of evidence: 3iiiD]
RFA also achieves best results in patients with tumors smaller than 3 cm. In this subpopulation of patients, 5-year OS rates may be as high as 59%, and the recurrence-free survival rates may not differ significantly from treatment with hepatic resection.[9,10] Local control success progressively diminishes as the tumor size increases beyond 3 cm.
In the few randomized, controlled trials that included patients with Child-Pugh A cirrhosis, RFA proved superior to PEI in terms of rates of complete response and local recurrences; some of those studies have also shown improved OS with RFA. Furthermore, RFA requires fewer treatment sessions than PEI to achieve comparable effects.[11-14]
Of note, RFA may have higher complication rates than PEI, but both techniques are associated with lower complication rates than excision procedures.
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with adult primary liver cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
- Llovet JM, Fuster J, Bruix J: Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology 30 (6): 1434-40, 1999. [PUBMED Abstract]
- Hemming AW, Cattral MS, Reed AI, et al.: Liver transplantation for hepatocellular carcinoma. Ann Surg 233 (5): 652-9, 2001. [PUBMED Abstract]
- Chok KS, Ng KK, Poon RT, et al.: Impact of postoperative complications on long-term outcome of curative resection for hepatocellular carcinoma. Br J Surg 96 (1): 81-7, 2009. [PUBMED Abstract]
- Kianmanesh R, Regimbeau JM, Belghiti J: Selective approach to major hepatic resection for hepatocellular carcinoma in chronic liver disease. Surg Oncol Clin N Am 12 (1): 51-63, 2003. [PUBMED Abstract]
- Poon RT, Fan ST, Lo CM, et al.: Long-term survival and pattern of recurrence after resection of small hepatocellular carcinoma in patients with preserved liver function: implications for a strategy of salvage transplantation. Ann Surg 235 (3): 373-82, 2002. [PUBMED Abstract]
- Dhir M, Lyden ER, Smith LM, et al.: Comparison of outcomes of transplantation and resection in patients with early hepatocellular carcinoma: a meta-analysis. HPB (Oxford) 14 (9): 635-45, 2012. [PUBMED Abstract]
- Huang GT, Lee PH, Tsang YM, et al.: Percutaneous ethanol injection versus surgical resection for the treatment of small hepatocellular carcinoma: a prospective study. Ann Surg 242 (1): 36-42, 2005. [PUBMED Abstract]
- Yamamoto J, Okada S, Shimada K, et al.: Treatment strategy for small hepatocellular carcinoma: comparison of long-term results after percutaneous ethanol injection therapy and surgical resection. Hepatology 34 (4 Pt 1): 707-13, 2001. [PUBMED Abstract]
- Huang J, Hernandez-Alejandro R, Croome KP, et al.: Radiofrequency ablation versus surgical resection for hepatocellular carcinoma in Childs A cirrhotics-a retrospective study of 1,061 cases. J Gastrointest Surg 15 (2): 311-20, 2011. [PUBMED Abstract]
- Zhou YM, Shao WY, Zhao YF, et al.: Meta-analysis of laparoscopic versus open resection for hepatocellular carcinoma. Dig Dis Sci 56 (7): 1937-43, 2011. [PUBMED Abstract]
- Lencioni RA, Allgaier HP, Cioni D, et al.: Small hepatocellular carcinoma in cirrhosis: randomized comparison of radio-frequency thermal ablation versus percutaneous ethanol injection. Radiology 228 (1): 235-40, 2003. [PUBMED Abstract]
- Lin SM, Lin CJ, Lin CC, et al.: Randomised controlled trial comparing percutaneous radiofrequency thermal ablation, percutaneous ethanol injection, and percutaneous acetic acid injection to treat hepatocellular carcinoma of 3 cm or less. Gut 54 (8): 1151-6, 2005. [PUBMED Abstract]
- Brunello F, Veltri A, Carucci P, et al.: Radiofrequency ablation versus ethanol injection for early hepatocellular carcinoma: A randomized controlled trial. Scand J Gastroenterol 43 (6): 727-35, 2008. [PUBMED Abstract]
- Shiina S, Teratani T, Obi S, et al.: A randomized controlled trial of radiofrequency ablation with ethanol injection for small hepatocellular carcinoma. Gastroenterology 129 (1): 122-30, 2005. [PUBMED Abstract]