New Hope For Liver Cancer Patients, UK

Main Category: Cancer / Oncology
Also Included In: Liver Disease / Hepatitis
Article Date: 24 Mar 2009 - 6:00 PDT

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A group of leading liver specialists has launched revised guidelines for the management of suspected hepatocellular carcinoma (HCC) in adults during a meeting at the Pelican Cancer Foundation in Basingstoke. Through the guidelines, the Hepatocellular UK Group (HUG) hopes to improve the prognosis of patients with a primary malignancy of the liver.

HCC is known to cause approximately 1,500 deaths per year in the UK, with up to 40 per cent of patients presenting with the cancer as the first indication of underlying liver disease. This is in stark comparison to countries such as Japan where 80 per cent of HCC cases are detected at an asymptomatic stage by screening of patients with known cirrhosis[1] HCC remains one of the commonest malignant diseases in the world but previously it has not been a leading cause of death in the Western world. There is now conclusive evidence from the USA, and a strong suggestion from the UK, that HCC is becoming a more common cancer, primarily due to the hepatitis C (HCV) epidemic.

The new guidelines cover two areas of clinical practice relating to HCC. The first is its diagnosis, including the surveillance of high-risk individuals, and the second is treatment of the patient where the diagnosis has been made.

Cancer care has been the subject of increased scrutiny with the development of care guidelines forming a major part of the strategy to reduce cancer related mortality in the UK. Both the Department of Health and the Health Development Agency are keen to encourage better detection of rare cancers.

Notes

1. This document on the management of patients with suspected hepatocellular carcinoma, was originally commissioned by the British Society of Gastroenterology (BSG) as part of a wider initiative to develop guidelines for clinicians in several areas of clinical practice. Initial guidelines were published in 2003 (Ryder 2003) and this document represents a revision in the light of new data and has been produced with input from a number of UK professional bodies involved in HCC patient management.

2. Guidelines are not rigid protocols and they should not be construed as interfering with local clinical judgement. Hence, they do not represent a directive of proscribed routes but a basis on which clinicians can consider the options available more clearly.

3. The HUG writing committee (with professional affiliations) comprised:

John Buckels (AUGIS)
Matthew Cramp (BASL)
James Garden (AUGIS)
Ashley Guthrie (BSGAR)
Stefan Hubscher (BSG Pathological section and RC Pathologists)
Philip Johnson (NCRI Upper GI-HepBil Clinical Studies Group)
John Karani (RCR & BSIR)
Derek Manas (BTS)
Dan Palmer (NCRI Upper GI-HepBil Clinical Studies Group)
Steve Pereira
Graeme Poston (BASO)
Raj Prasad (BTS)
Merv Rees (AUGIS & Federation of Gastroenterology)
Helen Reeves
Steve Ryder (BSG)

References:

Bosch FX, Munoz N. Hepatocellular carcinoma in the world: epidemiological questions. In Tabor E, Di Bisceglie AM, Purcell RH (eds): Etiology, Pathology and treatment of hepatocellular carcinoma. Portfolio, The Woodlands, Texas. 1991)

Ryder 2003 (BSC HCC guidelines)
Appendix 1

Summary of Recommendations

Surveillance for HCC:

- Surveillance using abdominal ultrasound and alpha-fetoprotein estimation can detect HCC of a smaller size than those presenting without screening (evidence IIa).

- The only potentially curative therapies depend on detection of small HCC (evidence IIa).

- Despite the above, there is no data confirming that these advantages in detection of earlier lesions produces an improvement in long-term survival or cost saving (Evidence IIa).

- Surveillance for hepatocellular carcinoma should be considered in all male and females with cirrhosis who might be suitable candidates for treatment (evidence grade III, recommendation grade B). The risk seems highest in cirrhosis due to hepatitis B, hepatitis C and genetic haemochromatosis (evidence grade III, recommendation grade B)

- If surveillance is offered, it should be using six monthly abdominal ultrasound assessments in combination with serum alpha-fetoprotein estimation (evidence grade III, recommendation grade B). Abdominal ultrasonography should be undertaken with appropriate dedicated equipment and by an operator skilled in the assessment of patients with cirrhosis (evidence grade IIb, recommendation grade B).

- If surveillance is offered, patients should be aware of the implications of early diagnosis and the lack of proven survival benefit

- Screening and surveillance should be performed where possible at dedicated (level 1) centres experienced in ultrasound imaging (evidence grade IV)

Diagnosis of HCC:

- Any patient with suspected HCC should be discussed at the regional multidisciplinary team (MDT) for hepato-biliary cancer as outlined in the National Cancer Plan

- Patients with suspicious lesions should be referred within 7-14 days for immediate assessment and diagnostic tests (CT scan and AFP) at specialist liver centres, with diagnostic tests completed within 32 days in order to meet the 62 day target for cancer diagnosis and initiation of treatment

- A focal lesion in the liver of a patient with cirrhosis is highly likely to be HCC (evidence grade IIa).

- Initial assessment should be by spiral CT of liver (local spread) and thorax (metastases) such CT scans should be performed to agreed cancer network protocols (evidence grade IIa, recommendation grade B).

- MRI with contrast enhancement may increase accuracy of detection of other liver lesions (evidence grade III, recommendation grade C). Such scans should again be to a formal agreed protocol across the cancer network.

- CT evidence of nodules plus AFP > 400 is suggestive of HCC

- Biopsy is rarely required for diagnosis as this can usually be established radiologically, and seeding of tumour in the needle tract occurs in 1-3%. Biopsy of potentially operable lesions should be avoided where possible although biopsy may be required in areas of significant doubt, this should only be performed after specialist review at a hepato-biliary MDT (evidence grade IIa, recommendation grade B).

Treatment of HCC:

The only proven potentially curative therapy for HCC remains surgical, either hepatic resection or liver transplantation and patients should always have these modalities of treatment considered.

- Patients with suspected HCC should be diagnosed and assessed for treatment within the 62 day target

- Liver transplantation should be considered in any patient with cirrhosis and a small (5cm or less single nodule, or up to five lesions of 3cm or less) or in patients with a single lesion greater than 5cm and less than or equal to 7cm diameter where there has been no evidence of tumour progression (volume increase by <20%; no extrahepatic spread; no new nodule formation) over a 6 month period. Locoregional +/- chemotherapy may be given during that time. Locoregional therapy should be considered for all transplant list cases (evidence grade IIa, recommendation grade B).

- Hepatic resection should be considered as primary therapy in any patient with HCC and a non-cirrhotic liver (including fibrolamellar variant) (evidence grade IIa, recommendation grade B)

- Resection can be carried out in highly selected patients with hepatic cirrhosis and well preserved hepatic function (Child-Pugh A). Such surgery carries a high risk of post-operative decompensation and should be undertaken in units with expertise in hepatic resection and management of liver failure and in consultation with a liver transplant unit (evidence grade IIa, recommendation grade B).

Non-surgical management:

Non-surgical therapy should only be used where surgical therapy is not possible. The techniques used are highly operator-dependant and should only be undertaken in accredited HPB units with sufficient expertise.

- Radiofrequency ablation has been shown to be effective therapy in HCC less than 3cm in diameter (evidence grade IIb). Percutaneous ethanol injection (PEI) has been shown to produce necrosis of small HCC. It is best suited to peripheral lesions, less than 3cm in diameter (evidence grade IIb, recommendation grade B) and has been shown to be inferior to RFA in local tumour control. It may still have a role in specialist centres for small lesions difficult to treat with RFA.

- Chemoembolisation can produce tumour necrosis and has been shown to affect survival in highly selected patients with good liver reserve. Chemoembolisation using lipiodol is effective therapy for pain or bleeding from HCC (evidence grade IIa, recommendation grade B).

Systemic therapy for HCC:

- Sorafenib has been shown to prolong survival in patients with advanced HCC and is the standard of care for patients with advanced HCC for whom no potential curative option is available (evidence 1b, recommendation grade A).

- Systemic chemotherapy with standard agents has a poor response rate (evidence grade I, recommendation grade A).

Source
Hepatocellular UK Group