Treatment of liver metastases, an update on the possibilities and results

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Abstract

Long-term results after liver resection for colorectal liver metastases show 5-year survival rates between 35 and 40%. However, only a limited number of patients appear to be candidates for resection, far more patients prove to have unresectable disease. Present challenges in liver surgery for colorectal metastases are to improve patient selection, to increase the resectability rate and to improve survival by multimodality treatment approaches. The variables most consistently associated with a poor prognosis and tumour recurrence are tumour-positive resection margins and the presence of extra-hepatic disease. Hence, patient selection and preoperative staging should concentrate on accurate imaging of the liver lesions and the detection of extrahepatic disease. For liver imaging, spiral computed tomography (CT) scan or magnetic resonance imaging (MRI), supplemented by intra-operative ultrasound, are currently regarded as the best methods for evaluating the anatomy and resectability of colorectal liver metastases. Extrahepatic disease should be investigated by spiral CT of the chest and abdomen and when possible by 2-fluouro-2-deoxy-d-glucose-positron emission tomography (FDG-PET). Resection remains the gold standard for the surgical treatment of colorectal liver metastases. In experienced centres, resection is a safe procedure and mortality rates are below 5%. The aim of resection should be to obtain tumour-negative resection margins. Edge cryosurgery should be considered in cases where very close resection margins are anticipated. The role of adjuvant chemotherapy after resection is still controversial, although two recent studies show a clear benefit. For the moment, local tumour ablative therapies such as cryotherapy and radiofrequency therapy should be considered as an adjunct to hepatic resection in those cases in which resection can not deal with all of the tumour lesions. In these cases, there seems a beneficial effect of a combined treatment consisting of resection and local tumour ablation. At this stage, there are no randomised data that local tumour ablation is as effective as resection. For a selected group of patients with unresectable liver metastases, there may be a chance to turn unresectable disease to resectable disease by aggressive neo-adjuvant chemotherapy or portal vein embolisation. For patients with unresectable disease, many different chemotherapy schedules may be used based on systemic drug administration. Regional chemotherapy and isolated liver perfusion should only be used within a study design.

Introduction

Colorectal cancer ranks second as a cause of death due to cancer in the Western world. The cumulative lifetime risk is approximately 5%, the incident rate in the Western world 50/100 000 [1]. Liver metastases form the main cause of death in patients with colorectal cancer. Already at the time of detection of the primary tumour, 15–25% of the patients present with liver metastases, another 20% will develop these metastases following treatment of the colorectal primary 2, 3. Without any treatment, the median survival after the detection of liver metastases is approximately 9 months, depending on the extent of the disease at the time of diagnosis [4].

In contrast to many other solid tumours, resection of liver metastases from colorectal origin has been shown to result in long-term survival and even cure. In selected patients with metastatic disease confined to the liver, 5-year survival rates are generally reported between 35 and 40%, depending on the extent of liver involvement 5, 6, 7, 8. Unfortunately, only a minority of patients (10–15%) with liver metastases are considered to be candidates for resection. Most patients have liver metastases that are unresectable. Present challenges in liver surgery are to improve patient selection, to increase resectability rates, and to improve survival by multimodality approaches of treatment.

Section snippets

Patient selection

In the past, several factors were identified that determined clinical outcome after resection of colorectal liver metastases (Table 1). The variables most consistently associated with poor prognosis and tumour recurrence are tumour-positive resection margin of the removed specimen and extrahepatic disease at the time of surgery for liver metastases 6, 7, 8, 9, 10, 11.

Preoperative staging

Preoperative staging of patients with colorectal liver metastases should concentrate on the accurate imaging of the number, size and location of the metastatic lesions within the liver, as well as on the detection of possible extrahepatic disease.

Survival

Resection is still the gold standard for the surgical treatment of colorectal liver metastases. It should be considered in all patients with metastatic disease confined to the liver which can be removed adequately, while leaving enough functional liver reserve.

Many studies over the last two decades have demonstrated long-term survival after liver resection for colorectal liver metastases (Table 2). 5-year survival rates after resection in these series varies from 21 to 50% 6, 7, 8, 9, 10, 11, 35

Local tumour ablation

In many patients with colorectal liver metastases confined to the liver, resection of the metastases can not result in an adequate clearance of all of the tumour tissue from the liver. This may be the case either because of the number of metastatic liver lesions or because of the location of the metastases. Examples are patients with more diffuse bilobar disease or with unresectable recurrence after previous liver surgery. It is in this group of patients with unresectable colorectal liver

Preoperative chemotherapy

Obviously there are many patients with metastastic disease confined to the liver and with a good performance status in whom liver involvement by tumour is either too extensive for surgery or in which tumour lesions are situated at unresectable sites. Several studies have shown that in some of these patients combination chemotherapy may alter unresectable lesions into resectable ones. In these studies, a schedule with 5-FU/LV/oxaliplatin has generally been used 70, 71, 72, 73, 74. In analyses

5-FU/LV

In Europe, until recently the standard first-line treatment in advanced colorectal cancer consisted of 5-fluorouracil (5-FU)-based schedules, in which almost invariably leucovorin (LV) is incorporated 86, 87, 88, 89, 90. Leucovorin enhances the activity of 5-FU which results in response rates of approximately 20% and a median overall survival of approximately 12 months. Many different schedules have been compared in randomised studies, showing differences in response rates and toxicity, but no

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