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Liver Cancer
Colorectal Liver Metastases—Enhancing Outcomes
Through Combination Treatments
Irving Taylor, MD, PhD
Professor of Surgery, Vice Dean, and Director of Clinical Studies, Division of Surgery and Interventional Science, University College London
Abstract
Colorectal liver metastases are common and should be considered for treatment in a multidisciplinary setting. Surgery is the treatment of
choice providing the metastases are resectable. In recent years the benefit of neoadjuvant chemotherapy has been established to downstage
metastases and render them amenable to surgical excision. This aspect, as well as the role of adjuvant chemotherapy, is discussed and critically
appraised in this article.
Keywords
Colorectal liver metastases, neoadjuvant treatment, adjuvant treatment
Disclosure: The author has no conflicts of interest to declare.
Received: August 4, 2008 Accepted: April 6, 2009
Correspondence: Irving Taylor, MD, PhD, Professor of Surgery, Vice Dean, and Director of Clinical Studies, Division of Surgery and Interventional Science, Unversity College London
Medical School, 74 Huntley Street, London WC1E 6AU, UK. E:
irving.taylor@ucl.ac.uk
Colorectal liver metastases (CRLMs) are common and can either suitable for surgical resection.
3
As a result, an attempt to increase the
present at the time of initial colorectal cancer diagnosis resectability rate with additional treatments has been advocated.
(synchronous) or develop later (metachronous). There has been
increasing interest in the treatment of CRLMs in recent years due to Neoadjuvant Chemotherapy
the development of new therapies and improving prognoses. A major There is increasing interest in the role of pre-operative or neoadjuvant
factor in the treatment of CRLMs is the need for detailed discussion chemotherapy to downsize liver metastases in an attempt to achieve
of individual patients in a multidisciplinary environment involving resection of previously unresectable CRLMs. Accordingly, such treatment
specialists with a wide range of interests. Accordingly, a treatment increases the proportion of patients able to achieve long-term survival.
plan and follow-up can be devised at an early stage. The importance Recent studies have described resection rates of up to 20% in patients
of this approach cannot be overemphasized. with initially unresectable liver metastases, with five-year survival rates in
these patients approaching 50% (see Table 1).
4–7
However, it should be
Surgery emphasized that in order to achieve optimum results, careful selection is
Surgery is the most important treatment modality for patients with essential. Recent studies have demonstrated a strong correlation
CRLMs. Appropriate surgery in selected patients will result in long-term between response rate to chemotherapy and subsequent resection rate,
survival of up to 40%;
1,2
this percentage has increased over the last two which in selected patients may be 20–50% compared with 1–20% in non-
decades. There have been developments in surgical technique, including selected patients. As shown in Table 1, various chemotherapy regimes
portal vein embolization and safer liver division and resection, as well as have been advocated and several have been subjected to prospective
improvements in post-operative management. As a result, resections clinical trials. The overall conclusions are, in summary: folinic acid,
are now more extensive and, due to improving expertise, are associated fluorouracil, and irinotecan (FOLFIRI) and 5-fluorouracil (5-FU), leucovorin,
with reduced post-operative morbidity and mortality. A general principle and oxaliplatin (FOLFOX) are equally effective (response rates of 56 and
is to resect all macroscopic disease, aiming for a potentially curative 54%, respectively
8
), and 5-FU, leucovorin, oxaliplatin, and irinotecan
resection. In order to achieve this, it may be necessary to combine (FOLFOXIRI) is superior to FOLFIRI
9
(response rates of 60 and 34%,
surgical excision with ablation, e.g. radiofrequency ablation, intra- respectively, and radical resection rates of 36 and 12%, respectively).
operatively or percutaneously, in the post-operative period. Often this Other studies have demonstrated response rates between 8 and 41%
avoids an unacceptably dangerous major resection; for example, an following administration of oxaliplatin- or irinotecan-based regimes; again,
extended right hemi-hepatectomy can be combined with in these terms selection may be crucial. It would appear that three-drug
radiofrequency ablation of smaller lesions on the left side of the liver. combinations have a higher response rate and a higher resection rate,
However, it should be noted that initially only 15–20% of patients are without any significant impact on either toxicity or surgical safety. These
70 © TOUCH BRIEFINGS 2009
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