Stages 0, A, and B Adult Primary Liver Cancer Treatment
Localized hepatocellular carcinomas (HCCs) that present as a solitary mass in a portion of the liver or as a limited number of tumors (≤3 lesions, ≤3 cm in diameter) without major vascular invasion constitute approximately 30% of the HCC cases.
There are three potentially curative therapies that are acceptable treatment options for small, single-lesion HCC in patients with well-preserved liver function.
Standard treatment options for stages 0, A, and B adult primary liver cancer include the following:
Resection and transplantation achieve the best outcomes in well-selected candidates and are usually considered to be the first option for curative intent.
Surgery is the mainstay of HCC treatment.
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.
Surgical resection can be considered for patients who meet the following criteria:
- 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.
After considering the location and number of tumors, and the hepatic function of the patient, only 5% to 10% of patients with liver cancer will prove to have localized disease amenable to resection.[1-5]
The principles of surgical resection involve obtaining a clear margin around the tumor, which may require any of the following:
- Segmental resection.
- Hormone-lymphatic lobectomy.
- Extended lobectomy.
In patients with limited multifocal disease, hepatic resection is controversial.
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.
According to the Milan criteria, patients with a single HCC lesion smaller than 5 cm, or 2 to 3 lesions smaller than 3 cm are eligible for liver transplantation. Expansion of the accepted transplantation criteria for HCC is not supported by consistent data. Liver transplantation is considered if resection is precluded as a result of multiple, small, tumor lesions (≤3 lesions, each <3 cm), or if the liver function is impaired (Child-Pugh class B and class C). In patients who meet the criteria, transplantation is associated with a 5-year OS rate of approximately 70%.[Level of evidence: 3iiiA]
When tumor excision, either by transplant or resection, is not feasible or advisable, ablation may be used if the tumor can be accessed percutaneously or, if necessary, through minimally invasive or open surgery. Ablation may be particularly useful for patients with early-stage HCC that is centrally located in the liver and cannot be surgically removed without excessive sacrifice of functional parenchyma.
Ablation can be achieved in the following ways:
- Change in temperature (e.g., radiofrequency ablation [RFA], microwave, or cryoablation).
- Exposure to a chemical substance (e.g., percutaneous ethanol injection [PEI]).
- Direct damage of the cellular membrane (definitive electroporation).
With ablation, a margin of normal liver around the tumor should be considered. 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 procedure. Furthermore, when tumors are located adjacent to major vessels, the blood flow in the vessels may keep thermal ablation techniques, such as RFA, from reaching optimal temperatures. This is known as the heat-sink effect, which may preclude complete tumor necrosis.
RFA 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.[7,8] Local control success progressively diminishes as the tumor size increases beyond 3 cm.
PEI obtains good results in patients with Child-Pugh class A cirrhosis and a single tumor smaller than 3 cm in diameter. In those cases, the 5-year OS rate is expected to be as high as 40% to 59%.[9,10][Level of evidence: 3iiiD]
In the few randomized, controlled trials that included patients with Child-Pugh class A cirrhosis, RFA proved superior to PEI in 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 outcomes.[11-14]
Of note, RFA may have higher complication rates than PEI, but both techniques are associated with lower complication rates than excision procedures. RFA is a well-established technique in the treatment of HCC.
Treatment Options Under Clinical Evaluation for Stages 0, A, and B adult primary liver cancer include the following:
- Definitive electroporation.
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage 0 adult primary liver cancer (BCLC), stage A adult primary liver cancer (BCLC) and stage B adult primary liver cancer (BCLC). 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.
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- 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]
- Hemming AW, Cattral MS, Reed AI, et al.: Liver transplantation for hepatocellular carcinoma. Ann Surg 233 (5): 652-9, 2001. [PUBMED Abstract]
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- 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]
- 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]
- 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]