Current PerspectiveTowards a pan-European consensus on the treatment of patients with colorectal liver metastases
Introduction
Colorectal cancer (CRC) is fourth in the league of cancer deaths worldwide with nearly 204,000 deaths in Europe alone each year.1 Approximately 25% of CRC patients present with overt metastases, and an additional 25–35% of patients will develop metastases during the course of their disease.2 Significantly between 20% and 30% of patients with advanced CRC have liver only metastases,3 while approximately 50% of recurrences following resection of the primary tumour are confined to the liver.4
Despite the recent advances in first-line chemotherapy strategies for the treatment of patients with advanced CRC,5, 6, 7, 8, 9 liver resection offers the only chance of cure for patients with colorectal liver metastases.10 Five-year survival rates following resection range between 25% and 40% compared with between 0% and 5% for patients from the same institute who did not undergo liver resection,4, 10, 11, 12, 13, 14, 15 and are consistent with the 5-year survivals reported for most large series where liver resection has been performed.16, 17, 18, 19 However, approximately 85% of patients with stage IV CRC, referred to specialist centres, have metastatic liver disease which is considered to be unresectable at presentation.20
Over the last five years, there has been a recognition that the improved combination chemotherapy regimens, namely 5-fluorouracil/folinic acid (5-FU/FA) in combination with either irinotecan or oxaliplatin,5, 6, 7, 8, 9 routinely used in the treatment of patients with advanced CRC, can facilitate the downsizing of colorectal liver metastases and render initially unresectable metastases resectable.18, 20, 21, 22, 23 Consequently, the percentage of patients potentially eligible for curative liver resection is increasing. Significantly also, the long-term survival rates for those patients with initially unresectable metastases treated with chemotherapy prior to surgery18 are similar to those of patients whose metastases were considered to be resectable (Fig. 1).13, 17, 19, 24 The results of a recent study, however, suggest that the recurrence rate may be quite high for these patients.25
However, despite these advances the selection criteria for the resection of CRC liver metastases are not well documented. Consequently, the possibility of resection of CRC liver metastases is often underestimated, and currently even in Europe, we have the situation where away from specialist centres, many patients with liver metastases are considered to be incurable and many patients with curable liver metastases are never referred to a surgeon.26 Conversely, in centres that specialise in liver resection we can have the situation where some patients who are incurable undergo resection.
The goal of a multidisciplinary treatment approach in this context is to increase cost-effectively the number of patients with long-term survival by increasing the number of patients undergoing potentially curative liver resections (Fig. 2). The first question that we need to address is: ’How do we establish guidelines that will facilitate this process and that can be readily adopted by the surgeons and medical oncologists, across Europe, working both inside and outside of specialist centres?’ Specifically, how do we prepare generally applicable guidelines to optimise the chances of survival of CRC patients with liver metastases?
Section snippets
Current status
Although there are several published clinical scoring systems,15, 19, 24, 27, 28, 29, 30 the French recommendations for clinical practice with regard to the ‘Therapeutic management of liver metastases from colorectal cancer’ published in March 2003,31 are by far the most comprehensive. Already in 2005–2006 we have moved on from the French recommendations,31 in terms not only of what is considered to be surgically resectable disease but also in terms of the recognition of the potential efficacy
The role of surgery
Historically, surgical resection of CRC liver metastases has been the sole treatment modality to achieve long-term survival in patients with stage IV CRC, with approximately 25–40% of patients who undergo R0 liver resection (i.e. rendered macroscopically disease free) alive at five years (Fig. 1).13, 19, 30, 32 However, only approximately 15% of patients with liver metastases are resectable at presentation (Fig. 1).
Until recently, the classic contraindications for resection of CRC liver
The role of perioperative chemotherapy
The use of perioperative chemotherapy in patients with liver only metastases is used in two clearly defined treatment settings. The first of these is in the preoperative, neoadjuvant setting to render initially unresectable metastases resectable and the second in either the adjuvant or neoadjuvant settings to reduce the risk of recurrence in patients with resectable metastases.
Conclusions
This meeting of the European Colorectal Metastases Treatment Group provided clear evidence that the field of liver resection for CRC liver metastases is progressing rapidly and that an ever-increasing number of patients can either be considered, or rendered eligible, for liver resection. However, there was also the recognition that despite this progress many patients with metastases are considered to be incurable and are not recommended for surgery. There needs therefore to be an insistence on
Conflict of interest statement
None declared.
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- h
Both contributed equally.
- i
Other members of the European Colorectal Metastasis Treatment group: Dag Arvidsson, Sweden, Karolinska Institute; Alfredo Carrato, Spain, Elche University Hospital; Joan Figueras, Spain, Hospital Trueta; Vassilis Georgoulias, Greece, University General Hospital of Heraklion; Bengt Glimelius, Sweden, University of Uppsala; Markus Golling, Germany, University Hospital Frankfurt/Mainz; Felice Giuliante, Italy, Catholic University of the Sacred Heart; Bernard de Hemptinne, Belgium, Ghent University; John Papadimitriou, Greece, Athens University; Josep Tabernero, Spain, Vall d’Hebron University Hospital; Harpreet Wasan, UK, Hammersmith Hospital.