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Hepactic resection as a treatment for liver metastases in colorectal cancer |
Beard S M, Holmes M, Majeed A, Price C |
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Authors' objectives To review the current state of evidence for the effectiveness of liver resection in cases of metastases related to colorectal primary lesions with particular reference to the likely characteristics of good prognosis groups and the likely impact that such patients may have on NHS resources.
Searching MEDLINE, EMBASE, the Cochrane Library, HMIC (Department of Health/King's Fund/HELMIS) and the NHS Centre for Reviews and Dissemination's databases (DARE, NHS EED and HTA) were searched from 1984 to 1998. Websites, personal contacts and other literature databases were also searched. Search terms and example search strategies are presented. Consideration was only given to the latest published data covering specific patient cohorts.
Study selection Study designs of evaluations included in the reviewCase series which reported survival results in more than 100 patients.
Specific interventions included in the reviewSurgical resection of liver metastases. The following types of resection were used: anatomic (common and uncommon), atypical minor, atypical major, wedge, lobectomy, segmental, lateral segmental, extended, major, minor, combined, non-anatomic, single lobe segmental, right or left hemi-hepatectomy.
Participants included in the reviewPeople with liver metastases related to primary colorectal cancer. Mean age at operation was around 60 years and similar numbers of men and women were studied.
Outcomes assessed in the reviewOverall survival, disease-free survival, operative morbidity, operative mortality and/ or pre-operative prognostic factors.
How were decisions on the relevance of primary studies made?The authors do not state how the papers were selected for the review, or how many of the reviewers performed the selection.
Assessment of study quality The authors do not state that they assessed validity.
Data extraction It is not stated how many reviewers extracted data or how disagreements were resolved. Data were extracted on: country of publication, time period of study, study design and method, number of patients, age, description of intervention, type of resection, adjuvant treatment, length and completeness of follow-up, outcomes, possible prognostic factors.
Methods of synthesis How were the studies combined?A narrative synthesis of the studies was presented.
How were differences between studies investigated?The authors do not state that they investigated differences between the studies.
Results of the review 21 case series (n = 6608). However, 2 of the 21 are subsets of larger case series, so only 19 separate studies are included (n = 5765).
Based on the reported survival outcomes for the treated populations as a whole, five year survival following surgical resection ranges between 21% and 41% (compared with < 5% in similar patients without surgical intervention). The best prognosis group is those with single metastases, without evidence of extrahepatic involvement. However sub-group analysis with case series suggests that despite the number and size of tumours there are clear survival advantages for patients with multiple metastases if the resection can successfully remove all of the metastases without leaving positive margins. The more recent, larger single centred studies report operative mortality rates of around 0-4% (as opposed to 4-8% reported by series from the late 1980s and very early 1990s) and post operative complications rates of 10-30%.
Cost information The costs of liver resection are estimated at £6,402 which covers initial work-up, the surgical procedure and the post-surgical management of patients. The typical systemic chemotherapy for non-resected patients is based on 5-FU and is estimated to cost £2,223 per month with an average 3-6 months' treatment per patient.
The estimated marginal costs of providing liver resection within a 'typical' health authority of 500,000 population are £130-135,000, based on an estimated 10% of patients being suitable for resection. This assumes that there is no avoidance of chemotherapy costs. In some cases however surgical resection would obviate the need for palliative chemotherapy.
Excluding any savings that may be made through avoided chemotherapy treatment and assuming no differences in salvage treatment for relapses, the cost per life-year gained (LYG) for liver resections is in the range £2,134 - £3,945 per LYG. This figure is dependent on the actual proportion of resections which can be performed with curative intent. The range quoted covers 100% to 50% of resections having curative intent and reflects the range of reported experience from case-series. Authors' conclusions No randomised controlled trial data or comparative group studies exist that examine the case for liver resection in the treatment of colorectal liver metastases. The evidence available is based on well conducted published case series of patients who have had resection of hepatic metastases for colorectal cancer, and comparisons are limited to historical comparative data about the outcome for patients who have had other forms of non-surgical treatment.
In general, uncontrolled non-randomised observational studies are more associated with over/under estimation of treatment effects than those that may be suggested through fully randomised controlled trials. When using observational study evidence, conclusions can be drawn using statistical comparisons such as meta-analysis, however such methods carry dangers in terms of confounding factors and study bias.
Based on the available evidence, there appears to be clear survival advantage for patients who have liver resection, provided that the surgery renders the patient tumour free (as far as can be judged on the basis of current investigations and microscopic examination of the resection margin) and they have no EHD. Although patients with multiple liver secondaries probably have a worse prognosis than those with a single metastasis, there is evidence of survival advantage from resecting these tumours provided that they have no EHD and all the tumour can be removed. The evidence does not provide good support for a survival advantage from surgery for patients who have liver resection when there is extrahepatic disease or in patients in whom all the tumour is not removed.
There is a significant survival advantage from operative techniques which minimise blood loss.
CRD commentary This is a reasonably good review. The research question and inclusion criteria are quite clear and the literature search is comprehensive. No details are given of the review process and validity of the studies is not assessed which leads to some difficulty in interpreting the results. Details of included studies are given in an appendix and it seems appropriate not to pool the study data in a meta-analysis given the different types of liver resection and other variables in the included studies. The authors' conclusions do seem to follow from the results.
Implications of the review for practice and research Practice: The authors state that those patients most suited to resection are likely to have single metastasis with no extrahepatic disease or multiple metastases restricted to a single lobe with no extrahepatic disease. Survival will be strongly influenced by the ability of the surgeon to remove the tumour(s) clearly without any involvement in the resection margins. They state that there needs to be a clear set of referral guidelines for district general hospitals when dealing with cases of liver metastases. These guidelines should define clearly the treatment pathways open to the patient.
Research: The authors state that RCTs are not necessary in simple resection but are needed for more complex liver surgery, adjuvant chemotherapy following resection and combining resection with cryosurgery.
Bibliographic details Beard S M, Holmes M, Majeed A, Price C. Hepactic resection as a treatment for liver metastases in colorectal cancer. Sheffield: University of Sheffield, Trent Institute for Health Services Research. Guidance Notes for Purchasers; 99/02. 1999 Indexing Status Subject indexing assigned by CRD MeSH Colonic Neoplasms; Hepatectomy; Liver Neoplasms /surgery AccessionNumber 12000008029 Date bibliographic record published 31/10/2000 Date abstract record published 31/10/2000 Record Status This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn. |
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