One half of all patients with colorectal cancer will develop metastatic deposit(s) in the liver at some stage of their illness. For these patients with inoperable colorectal liver metastases (CLM), the condition can only be controlled with chemotherapy. The availability of newer agents such as oxaliplatin and irinotecan have brought better palliation (control) and thus improving survival. However, some patients will still become unresponsive to oxaliplatin, irinotecan or both. For these patients the outlook is grim. With the advent of molecular agents such as bavacizumab (Avastin) and cetuximab (Erbitux), these patients, who have become refractory to oxaliplatin or irinotecan, have another avenue of treatment which temporarily holds the disease at bay.

A recent study from Greece examined the efficacy of combining cetiximab with capecitabine and oxaliplatin in treating 40 patients with metastatic colorectal cancer whose disease progressed under oxaliplatin-based chemotherapy. With cetuximab, 20% of the patients showed evidence of response. Despite this, the median time to tumour progression was 3 months and the median survival was 10.7 months (Ann Oncol 2007; 18: 305 - 310). This study and many other studies emphasized the point that chemotherapy can only hold the cancer at bay for a period of time before the cancer becomes refractory to the drug. Hence, if the chemotherapy is effective and can convert an inoperable case to an operable case, aggressive surgery to remove all visible cancer from the body will then confer the chance of prolonged survival on these patients.

A recent study from France on CLM previously refractory to conventional chemotherapy examined the role of rescue cetuximab therapy in converting refractory, inoperable CLM to operable cases (J Clin Oncol 2007 25: 4593 – 4602). From February 2004 to April 2006, 151 patients with inoperable CLM who failed initial chemotherapy were treated with cetuximab + irinotecan, cetuximab + oxaliplatin or cetuximab + oxaliplatin + irinotecan. Following cetuximab-based therapy, 27 patients underwent surgery. Twenty five of the 27 patients were able to undergo liver resection to remove the CLM. After a median follow-up of 16 months, 23 of 25 patients who underwent liver resection (92%) were alive and 10 patients (40%) were disease free.

What does the French study tell us about CLM refractory to first and second line chemotherapy? In order to give patients with CLM a chance to live longer and potentially be cured as well, aggressive surgery to remove all visible signs of disease in the liver is necessary. If we just use cetuximab without surgery, the CLM will progress with time. While it is understandable that most patients are fearful of undergoing liver surgery, liver surgery is the only means to give these patients the chance of prolonged survival.

Primary liver cancer or hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. It is the most dreaded complication to afflict any hepatitis B virus (HBV) carrier. In the majority of cases, HCC occurs on a background of liver cirrhosis (hardening of the liver). Alcoholism, chronic infection with hepatitis B and C virus are common aetiological agents for liver cirrhosis worldwide. HCC can grow to a large size or an advanced stage before any symptoms become obvious. Thus, in a large majority of HCC cases, no curative treatment can be offered at the time of diagnosis, either because the tumour is at an advanced stage or the liver function is poor due to the underlying liver cirrhosis. (The curative treatments for HCC are surgical resection and liver transplantation. Liver transplantation is only an option in about 10% of patients.)

Regular surveillance with ultrasound scanning and measurement of the serum alphafetoprotein (AFP) level has been shown to detect HCC at an earlier stage in oriental HBV carriers. Patients with cirrhosis are classified as Child-Pugh class A, B or C patients. Essentially the classification is based on 3 liver functions and 2 clinical parameters. Class A patients have very good liver function, B patients have intermediate function and C patients have poor liver function. Contrary to the Eastern experience, surveillance is normally only thought to be effective and meaningful for the Child-Pugh class A Western population. However, a recent study from Italy has concluded otherwise (Am J Gastroenterol 2007; 102: 2448 – 2457).

Two groups of patients with class B and C cirrhosis were studied. Group 1 patients, 252 of them, were found to have HCC during regular surveillance with liver ultrasound and measurement of AFP level. In group 2, 356 patients with HCC were detected incidentally; that is, detected outside any surveillance prgramme or during examination for other diseases. Group 1 patients were diagnosed at a younger age than group 2 patients. At diagnosis, 62.3% of the patients in Group 1 had early HCC compared to only 26.2% in group 2. Detection of early stage HCC is translated into more radical treatment options such as surgery or local destructive treatment. Thirty five percent of group 1 patients had radical treatment while only 17.9% of group 2 patients were treated this way. More than half (51.2%) of group 2 patients received only systemic or palliative treatment versus 29.2% of group 1 patients. The median survival was 17.1 months for group 1 patients and 12 months for group 2 patients. The estimated survival rates at 1, 3 and 5 year were 60.4% vs 49.2%, 26.1% ys 16.1% and 10.7% vs 4.3%; group 1 vs group 2, respectively.

Two weeks ago, a lady in her mid 30s was referred to me with a 17 cm HCC in her liver. She has a young family and is a known HBV carrier (with other older siblings who are HBV carriers) but did not go for regular surveillance. She first sought medical advice when she experienced upper abdominal pain and that was when the 17 cm HCC was discovered. Radical treatments are not an option. Her prognosis is grave.

A regular surveillance programme for patients with HBV infection and / or liver cirrhosis is very important. Surveillance leads to earlier detection of the HCC and thus allows clinicians treat the condition aggressively. HCC can grow to a large size or an advanced stage before symptoms appear. Thus, HBV carriers, with or without liver cirrhosis, who do not participate in a regular surveillance programme but rely on symptoms to alert them that something is wrong will usually face a much poorer outcome.

If you are an HBV carrier or have a cirrhotic liver, do go for regular surveillance at 6 monthly intervals. Do not be tempted to skip an appointment or two just because your last few surveillance scans and blood tests were normal. You may well not live long enough to regret those omissions!