Debates on Treatment Order of Colorectal Cancer with Liver Metastases

Debates on Treatment Order of Colorectal Cancer with Liver Metastases

Derek A O’Reilly, Graeme J Poston, Hassan Z Malik


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Colorectal cancer is estimated to cause 57,100 deaths per annum in the US and 17,000 deaths per annum in the UK.1,2 The liver is usually the first site of metastatic disease and may be the only site in 30–40% of patients with advanced disease.3 Unfortunately, at the time of initial diagnosis of colorectal cancer 20–25% of patients will already have clinically detectable colorectal liver metastases (CRLM), and the figure remains stubbornly at this rate despite increasing patient and clinician awareness of the disease.1,4,5

Historically, these patients have been considered to have a poorer prognosis than those subsequently found to have developed metachronous diseases.1,5 A further 40–50% will develop liver metastases, usually within the first three years of follow-up after successful resection of the primary tumour.1,4,5 Surgery remains the only treatment that offers the prospect of cure for CRLM. Until recently, only far fewer than 20% of these patients were considered suitable for attempted curative resection, the remaining patients being offered palliative and symptomatic treatment.6

This article focuses on a variety of recent strategies that have been designed to increase the pool of those patients presenting with synchronous metastatic disease for whom curative treatment may be possible. These include improved pre-operative staging techniques, new standards for surgical resection, novel surgical strategies, the application of modern systemic chemotherapy in a ‘neoadjuvant’ setting, an emerging role for ablative therapies and an emphasis on the collaborative, multidisciplinary management of this disease.

Pre-operative Staging – The Key to Selection of Candidates for Curative Treatment
Individual imaging techniques used in pre-operative staging have different strengths and weaknesses. One clear aspect of these rapidly advancing technologies has been the earlier detection of low-volume metastatic disease. From a pathological perspective, all metastases (those found at the time of initial presentation, and those subsequently found after an apparently ‘curative’ resection of the primary tumour) are synchronous to the time of diagnosis of primary colorectal cancer. It is only our ability to detect low-volume disease that is subsequently ‘metachronously’ diagnosed when the disease becomes clinically or radiologically overt that is evolving. Consensus is now emerging on the optimal choice of technique and the sequence in which they should be employed.7–10

Recent advances in computed tomography (CT) technology, such as helical CT and multidetector-row helical CT, have improved the performance of CT in terms of speed of acquisition, resolution and ability to image the liver during various phases of contrast enhancement with greater precision.7,10 Intravenous iodinated contrast media should be used routinely. These techniques help to characterise liver lesions based on their enhancement patterns during the various phases of contrast circulation in the liver.10 CT has limitations, including the need for a high radiation dose and low sensitivity for the detection and characterisation of lesions smaller than 1cm.

Magnetic resonance imaging (MRI) is a highly effective imaging modality for detecting and characterising liver lesions, as it provides high lesion-toliver contrast. Gadolinium, the most commonly used MRI contrast agent, behaves similarly to the iodinated contrast agents used in CT.7,10 Liver-specific contrast media, such as super paramagnetic iron oxide, further improve the contrast between liver and metastases.10,11 However, it is limited by low sensitivity for detecting extrahepatic disease in the peritoneum and chest.

Positron emission tomography CT has emerged as an important diagnostic tool in the evaluation of metastatic colorectal cancer. This modality is highly sensitive. However, any focal area of hypermetabolism (including inflammation and abscesses) can give false-positive results. Other disadvantages include high cost, poor lesion localisation and limited sensitivity for lesions smaller than 1cm.10,12

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