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Colorectal Cancer
Colorectal Liver Metastases – Enhancing Outcomes
Through Combination Treatments
Irving Taylor
Professor of Surgery, Vice Dean and Director of Medical Studies, 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 and the role of adjuvant chemotherapy are 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: 24 April 2008 Accepted: 3 May 2008
Correspondence: Irving Taylor, Division of Surgery and Interventional Science, UCL Medical School, University College London, 74 Huntley Street, London WC1E 6AU, UK.
E:
irving.taylor@ucl.ac.uk
Colorectal liver metastases (CRLMs) are common and can either Neoadjuvant Chemotherapy
present at the time of initial colorectal cancer diagnosis (synchronous) There is increasing interest in the role of pre-operative or neoadjuvant
or develop subsequently (metachronous). There has been increasing chemotherapy to downsize liver metastases in an attempt to achieve
interest in the treatment of CRLMs in recent years due to the resection of previously unresectable CRLMs. Accordingly, such
development of new therapies and improving prognosis. treatment increases the proportion of patients able to achieve long-
term survival. Recent studies have described resection rates of up to
A key factor in the treatment of CRLMs is the need for detailed 20% in patients with initially unresectable liver metastases, with five-
discussion of individual patients in a multidisciplinary environment year survival rates in these patients approaching 50% (see Table 1).
4–7
involving specialists with a wide range of interests. Accordingly, a plan However, it should be emphasised that in order to achieve optimum
of treatment and follow-up can be devised at an early stage. The results, careful selection is essential. Recent studies have demonstrated
importance of this approach cannot be overemphasised. a strong correlation between response rate to chemotherapy and
subsequent resection rate, which in selected patients may be 20–50%
Surgery compared with 1–20% in non-selected patients.
Surgery is the most important treatment modality for patients with
CRLMs. Appropriate surgery in selected patients will result in long- As shown in Table 1, various chemotherapy regimes have been
term survival of up to 40%.
1,2
This percentage has increased over the advocated and several have been subjected to prospective clinical
last two decades. There have been developments in surgical trials. The overall conclusions are, in summary: folinic acid, fluorouracil
technique, including portal vein embolisation and safer liver division and irinotecan (FOLFIRI) and 5-fluorouracil (5-FU), leucovorin and
and resection, as well as improvements in post-operative oxaliplatin (FOLFOX) are equally effective (response rates of 56 and
management. As a result, resections are now more extensive and, 54%, respectively
8
); and 5-FU, leucovorin, oxaliplatin and irinotecan
due to improving expertise, are associated with reduced post- (FOLFOXIRI) is superior to FOLFIRI
9
(response rates of 60 and 34%,
operative morbidity and mortality. A general principle is to resect all respectively, and R0 resection rates of 36 and 12%, respectively).
macroscopic disease, aiming for a potentially curative resection. In
order to achieve this, it may be necessary to combine surgical Other studies have demonstrated response rates of between 8 and
excision with ablation, e.g. radiofrequency ablation, intra-operatively 41% following administration of oxaliplatin- or irinotecan-based
or percutaneously in the post-operative period. Often this avoids an regimes. Again, selection may be crucial in this regard. It would
unacceptably dangerous major resection; for example, an extended appear that three-drug combinations have a higher response rate and
right hemi-hepatectomy can be combined with radiofrequency a higher resection rate, without any significant impact on either
ablation of smaller lesions on the left side of the liver. However, it toxicity or surgical safety. These studies are extremely important and
should be noted that initially only 15–20% of patients are suitable for demand our attention. Patients with apparently unresectable disease
surgical resection.
3
As a result, an attempt to increase the who are otherwise fit should be considered for neoadjuvant therapy
resectability rate with additional treatments has been advocated. in a multidisciplinary setting. The role of biological agents in this
70 © TOUCH BRIEFINGS 2009
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