Management

Management is highly dependent on tumour, patient and treatment factors. The main tumour factor is stage, particularly whether the tumour is potential resectable or not.

  • Tumour factors
    • Stage
    • Extent of liver involvement (ie. is the tumour potentially resectable while leaving at least 20% of the liver intact)
  • Patient factors
    • Overall health of patient
    • Health of liver (cirrhosis often makes surgery not possible)
  • Treatment factors
    • Treatment should be undertaken in tertiary institutions by experienced liver surgeons

Management of T1-T2 Disease

Treatment is guided by:

  • Underlying liver health (Child-Pugh score)
  • Overall patient health

Partial Hepatectomy (Child-Pugh A, Surgical Candidate)

Patients with Child-Pugh scores of A with focal disease and good overall health should undergo partial hepatectomy, which provides 5-year survival of 50%. Perioperative mortality is low (<5%). Local recurrence is not uncommon at 70%, and more likely when high risk features are present (positive margins, lymphovascular invasion, anaplasia).
The use of 131I-labeled lipiodol (an oil effusion) after surgical resection was evaluated in a randomised controlled trial. Although there was an initial survival advantage, this became negligible after 8 years follow up.

Liver Transplant (Child-Pugh B-C, Surgical Candidate)

Partial hepatectomy is associated with high mortality rates (> 30%) in these patients. Total hepatectomy offers the chance at both cure of cancer and cirrhosis. It has the best survival (70%) and relapse rates (15%) at 5 years. It is highly dependent on the availability of donor livers and the response of the tumour to neo-adjuvant therapies while awaiting transplant.

Non-Surgical Therapies

The non-surgical therapies have inferior control to surgery, but may be the patient's only option if they are not fit.

Radiofrequency Ablation

This popular method of treating patients unable to or instead of surgery involves introducing a probe into the tumour volume and deploying high levels of low frequency energy. This results in the cauterisation of the tissue. It avoids anaesthetic and some surgical risks. RFA is best used for smaller lesions (< 5 cm) but shows improved survival when compared to other local ablative therapies (ethanol, cyrotherapy). 5 year survival averages 40%.

Radiotherapy

Radiotherapy is used in the trial setting as treatment for focal hepatocellular carcinoma. Due to the low tolerance of liver to radiotherapy, it has been avoided in the past but advances in 3D conformal techniques, image guidance and stereotactic radiotherapy are allowing treatment to focal liver lesions. Radiotherapy has also been evaluated in locally advanced disease in combination with chemotherapy.
Multiple stereotactic trials are now becoming available, mostly case series. They are demonstrating effective control of hepatocellular carcinoma at rates similar to surgery for Child-Pugh A patients.

131I-labeled Lipiodol

This technique has been used in several studies. It remains a potential tool when small liver lesions are present but not amenable to resection, radiofrequency ablation or other treatments.


Management of Local Unresectable Disease (Stage IIIA-B)

These patients are incurable but local therapies may improve survival, mostly when they have good liver function (Child-Pugh A).

Hepatic Artery Embolisation

Trans-Arterial Chemo-Embolisation (TACE) is a popular treatment. It is suitable for patients with minimal tumour symptoms and Child-Pugh class A. In these groups, TACE has been shown to improve median survival in several randomised trials. Controversy exists as to the benefit, as a Cochrane review established that there was no evidence that TACE improved outcomes.
Newer methods of TACE include the use of drug-eluting beads rather than lipiodol (an oil based emulsion). This seems to improve delivery to the tumour and reduce toxicity to the liver and bone marrow with much lower rates reported.

TACE with Radiotherapy

TACE has been combined with external beam radiotherapy in several Asian studies. Meta-analysis of these studies has shown a survival advantage over TACE alone; only 5 of the included trials were randomised and radiotherapy does not seem to play a major role in hepatocellular carcinoma management at this time.

TAE with 90Yttrium Microspheres

A popular alternative to drug-eluting beads to 90Yttrium coated microspheres. These can be used in a similar method to TACE. There are no direct comparisons but survival ranges from . Toxicity seems to be improved compared to TACE but there are no direct comparative trials.


Management of Metastatic Disease (Stage IIIC-IV)

Metastatic disease is always fatal and conventional cytotoxic chemotherapy is typically ineffective. More recently, a trial employing sorafenib (SHARP trial) reported an improvement in progression free and overall survival (2 extra months) when compared to placebo.


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