Secondary Liver Cancer Causes, Symptoms, and Treatment

See also the separate Malignancy of Unknown Origin and Carcinomatosis articles.

What is secondary liver cancer?

The liver is one of the most common sites to which malignancies preferentially metastasise^[1].

Metastatic liver cancer is the most common cause of death in cancer patients. Complete surgical resection is currently considered the only curative liver metastases treatment, with only about 25% of patients being amenable to surgery^[2].

Lymph nodes are the most common site for metastatic malignant spread, with the liver next in frequency. The vulnerability of the liver for metastatic disease may be related to the fact that it is the largest organ in the body and it filters blood from both the systemic and the portal systems. Humoral factors promoting cell growth and blood flow are second only to the lungs.

Most liver metastases are multiple and affect both lobes. Single liver metastases occur in only a minority of patients. The most common primary sites for hepatic metastases are colorectal, stomach, pancreas, breast, lung and eye. In children, the most common primaries are neuroblastoma, Wilms' tumour and leukaemia. Most tumours that have spread to the liver have metastasised to other sites as well.

Secondary liver cancer symptoms

• Hepatomegaly and ascites are present in about half of patients with liver metastases. Nodularity may be palpable along the enlarged liver edge. Ascites indicates wide dissemination and a poor prognosis.
• Large liver metastases may block bile ducts and cause jaundice, malaise, anorexia and loss of weight.

Investigations

• Abnormal blood results may include anaemia and leukocytosis. Bilirubin, alkaline phosphatase and transaminase levels may be raised but LFTs are not always abnormal.
• A number of liver tumour markers have been identified, including alpha-fetoprotein (AFP), protein induced by vitamin K absence (PIVKA-II) and carcinoembryonic antigen (CEA).
• Useful immunohistochemical markers for the differential diagnosis of metastatic carcinomas in the liver include cytokeratins (CK7, CK19, and CK20), neuroendocrine markers (CD56, synaptophysin, and chromogranin A), and tissue-specific markers (CDX2, SATB2, TTF-1, GCDFP-15, mammaglobin)^[1].
• CXRs and abdominal ultrasound may be helpful; plain abdominal X-rays less so.
• Ultrasound (especially when enhanced with Doppler or colour-flow imaging). CT, MRI and positron emission tomography (PET) scanning may all be useful in varying circumstances.
• Angiography is essential if vascular intervention is planned.
• Liver biopsy is needed for an histological diagnosis. However, biopsy can lead to needle tract metastases and some argue that in Western populations where primary liver tumours are rare, investigation should focus on finding a primary source when investigating malignant liver lesions^[3]. Liver biopsy is not advised if the tumour is operable.

Differential diagnosis

See also the separate Benign Liver Tumours and Primary Liver Cancer articles.

Secondary liver cancer treatment and management

Treatment for metastatic liver cancer depends on the location and stage of the liver cancer and how well liver function is preserved. Treatment options include surgical resection, thermal ablation, systemic chemotherapy, transarterial chemoembolisation and selective internal radiation therapy.

Liver transplantation may be appropriate for some patients. For most patients with liver metastases, treatment with curative intent is not possible.

Surgery for secondary liver cancer

Hepatectomy for stage IV colorectal cancer is considered the standard of care for resectable isolated hepatic disease and acceptable performance status. However, the indications for resection of non-colorectal origin liver metastases are not as clearly defined^{[4, 5]}.

Partial hepatectomy to remove a single deposit may prolong survival. Patients with secondary liver cancer must be carefully selected and be free from extrahepatic metastases.

Recent but limited outcomes data on liver transplantation for unresectable hepatic metastases from colorectal cancer have claimed some survival benefit compared to the previous reports. However, there is a high rate of tumour recurrence within a very short time after liver transplantation^{[6, 7]}.

Other secondary liver cancer treatments

• Minimally invasive treatments, including freezing, ethanol and lasers, have also been used in the treatment of metastatic hepatic deposits. Radiofrequency ablation is a popular technique^{[8, 9]}. However, more trials are needed to look at its effectiveness^[10].
• Transcatheter arterial chemoembolisation (TACE) can block the blood supply to hepatic tumours, and microcatheters can be used to deliver chemotherapeutic agents.
• The National Institute for Health and Care Excellence (NICE) has advocated the use of laparoscopic liver resection for a solitary liver metastasis, for hepatocellular carcinoma (HCC) and for benign liver tumours and cysts^[11].
• Radiofrequency-assisted liver resection is supported by NICE^[12].
• NICE recommends that evidence on microwave ablation for treating liver metastases raises no major safety concerns and the evidence on efficacy is adequate in terms of tumour ablation^[13].
• NICE also endorses the use of ex vivo hepatic resection (operation on the liver outside the body followed by re-implantation) in patients who would otherwise die and have tried all other appropriate treatments^[14].
• NICE recommends that selective internal radiation therapy (SIRT) should be considered as a treatment option for non-resectable colorectal metastases in the liver^[15].
• NICE recommends that the evidence on the safety of melphalan chemosaturation with percutaneous hepatic artery perfusion and hepatic vein isolation for cancer or metastases in the liver shows there are serious, well-recognised complications. For patients with metastases in the liver from ocular melanoma, there is some evidence of short-term tumour response. However, for patients with primary liver cancer or metastases in the liver that are not from ocular melanoma, evidence of efficacy is inadequate in quality and quantity^[16].
• Chemotherapy may also be a treatment option depending on the primary site. However, if there is co-existing extensive extrahepatic disease, prognosis is usually guarded.

Secondary liver cancer prognosis

• Deposits from colorectal cancer seem to have a better prognosis.
• The prognosis will depend on the extent of liver metastases and other metastatic spread, the nature and stage of the primary cancer and comorbidities.
• People with secondary liver cancer do not usually die as a direct result of the liver metastases but for some other reason - for example, a chest infection or renal impairment.