Guidelines for Resection of Colorectal Cancer Liver Metastases
There has been increasing recognition of the potential benefits of liver resection for colorectal metastases in the UK although this treatment has been established more widely in other Western countries. There are no randomised studies assessing outcome following resection compared with no treatment or other therapeutic modalities in patients with known resectable liver metastases as it is generally considered unethical not to offer surgery for resectable disease. There has been increased interest in more aggressive chemotherapy regimens that have been reported to not only control metastatic disease but also to render some advanced liver metastases resectable. 1–4 Furthermore, other new modalities have become available that allow safe ablation of liver metastases without the need for surgical intervention. There is therefore a need to produce clear guidelines on the appropriate management of patients with colorectal cancer who have been shown to have hepatic metastases.
These guidelines are intended to address a number of issues:
(a) the principles under which patients with hepatic metastases should be managed;
(b) which patient s who have undergone attempted curative resection of the primary colorectal tumour should be offered surveillance;
(c) what investigations are required to determine appropriate management; and
(d) which treatment modality is most appropriate in a given clinical context.
The process of formulating any clinical guidelines requires a guideline development group, a search strategy with review of the relevant literature, synthesis of evidence (and consensus methods for topics when evidence is lacking), followed by external review. A multidisciplinary meeting with representation from a number of interested bodies involving surgeons, gastroenterologists, oncologists, diagnostic and interventional radiologists, pathologists, general practitioners, clinical nurse specialists, nurse practitioners, and patients was held in the Pelican Centre in Basingstoke on 2–4 October 2003 (see appendix 1). The Appraisal of Guidelines Research and Evaluation (AGREE) instrument was used to provide a framework for assessing the quality of the clinical practice guidelines. At this initial meeting, discussion resulted from individual presentations on aspects of hepatic metastases, a literature review, and expert re-evaluation. The literature review has been published in the British Journal of Cancer. 5 An initial group consensus was reached and a preliminary document produced before this was further refined by the group on 12 March 2004. This document has undergone subsequent expert external review and been amended accordingly. This guideline is not intended to serve as a standard of care as such standards are determined on the basis of all clinical data available for the individual case. It is recognised that they are subject to change with advances in scientific knowledge and technology and as patterns of care evolve. These parameters of clinical practice should be considered as guidelines only. The critical judgement regarding a particular clinical procedure or treatment plan has to be made by the doctor and the multidisciplinary team, following discussion of the options with the patient, and in the light of the diagnostic and therapeutic choices available. However, it is advised that significant departures from these guidelines be documented in the patient’s case records at the time the relevant decision is taken. This guideline was issued in 2005 and will be reviewed periodically and no later than 2008 to reflect any new evidence. The strength and evidence used in these guidelines was that used by the Agency for Health Policy Research (1992).
• Ia: evidence from meta-analysis of randomised controlled trials.
•Ib: evidence from at least one randomised controlled trial
• IIa: evidence from at least one controlled study without randomisation
• IIb: evidence from at least one other type of quasi-experimental study.
• III: evidence from non-experimental descriptive studies, such as comparative studies, correlation studies, and case control studies.
• IV: evidence from expert committee reports or opinions and / or clinical experience of respected authorities.
• A: directly based on category I evidence.
• B: directly based on category II evidence or extrapolated recommendation from category I evidence.
• C: directly based on category III evidence or extrapolated recommendation from category I or II evidence.
• D: directly based on category IV evidence or extrapolated recommendation from category I, II, or III evidence.
General
• Patients under consideration of treatment of hepatic metastases should be discussed at a multidisciplinary meeting which has experience in the management of liver metastases.
• A hepatobiliary multidisciplinary team (MDT) which carries out liver resection should be based in a cancer centre serving a population of at least two million. When two or three networks cooperate to create a single joint team, there should be explicit arrangements for referral between networks. (Category of evidence II ; strength of recommendation B)
• Consideration of patients for resection of liver metastases should be carried out at a single high volume centre. (Category of evidence II; strength of recommendation B)
At the Time of Presentation of Primary Colorectal Cancer
• Patients with primary colorectal cancer should have a computed tomography (CT) scan of the abdomen and pelvis performed with intravenous contrast and ideally a maximum collimation of 5 mm. This should be performed preoperatively or, in the case of an emergency, as soon as practical thereafter. (Category of evidence II; strength of recommendation B)
• A chest CT is ideal to assess the presence of pulmonary metastases but a chest x ray is considered satisfactory. (Category of evidence III; strength of recommendation C)
• The whole of the colon should be visualised to ensure a ‘‘clean colon’’. (Category of evidence II; strength of recommendation B)
• A baseline measurement of carcinoembryonic antigen (CEA) should be performed. (Category of evidence III; strength of recommendation
Following Curative Resection of Primary Colorectal Cancer
• Following treatment of the primary disease, some patients will prove to be unfit or unwilling to have further treatment and in such cases follow up is inappropriate.
• Other patients will prove to have metastatic disease at presentation. Some of these will have isolated liver metastases and should be managed as described in these guidelines.
• Patients undergoing R0 colorectal resection may be candidates for adjuvant chemotherapy and a further abdominal contrast enhanced CT (or magnetic resonance imaging (MRI)) should be performed following completion of chemotherapy. (Category of evidence III; Strength of recommendation C)
• Where possible patients over the age of 50 years should be considered for randomisation to the FACS trial, the UK NCRN trial of follow up strategies (synopsis in appendix 2).
• If the patient is ineligible for trial inclusion, does not wish to participate in the randomised trial, or if the unit is not recruiting to the trial, the following follow up schedule is appropriate :
(a) CT scan of the abdomen and pelvis should be undertaken as a minimum in the two years following completi on of treatment of the pri mary disease. (Category of evidence III; strength of recommendation C)
(b) Colonoscopy repeated after five years.
(c) The case for routine serial CEA measurements is unproven. (Category of evidence III; strength of recommendation
Further Staging Investigation to Detect Extrahepatic Involvement in Patients with Colorectal Liver Metastases
• For a patient discovered to have isolated liver metastases, CT of the chest, abdomen, and pelvis should be performed by the liver surgery unit or using protocols agreed with that unit. The liver surgery centre will also often perform liver specific imaging by local protocol.
• Biopsy of hepatic lesions should not be performed without discussion with the regional hepatobiliary unit. (Category of evidence III; strength of recommendation C)
• Patients with ‘‘high risk’’ primary disease (T4 (perforated); C2 (apical node)) should have careful preoperative investigations that might include positron emission tomography (PET) and laparoscopy. (Category of evidence III; strength of recommendation C)
Liver Resection for Colorectal Metastases
• The aim of liver resection (resectability) is to remove all macroscopic disease with clear (negative) margins and leave sufficient functioning liver. (Category of evidence II; strength of recommendation B)
• Patients with solitary, multiple, and bilobar disease who have had radical treatment of the primary colorectal cancer are candidates for liver resection. (Category of evidence III; strength of recommendation C)
• The ability to achieve clear margins (R0 resection) should be determined by the radiologist and surgeon in the regional hepatobiliary unit. (Category of evidence III; strength of recommendation C)
• The surgeon should define the acceptable residual functioning volume, approximately one third of the standard liver volume, or the equivalent of a minimum of two segments. (Category of evidence III; strength of recommendation C)
• The liver surgeon and anaesthetist should take the clinical decision regarding fitness for surgery. (Category of evidence III; strength of recommendation C)
• If deemed medically unfit for surgery, patients should be considered for ablative therapy. (Category of evidence IV; strength of recommendation D)
• Patients with extrahepatic disease that should be considered for liver resection include:
(1) resectable/ablatable pulmonary metastases;
(2) resectable/ ablatable isolated extrahepatic sites—for example, spleen, adrenal, or respectable local recurrence; and
(3) local direct extension of liver metastases to, for example, diaphragm/adrenal that can be resected. (Category of evidence IV; strength of recommendation D)
• Normal contraindications to liver resection would include uncontrollable extrahepatic disease such as:
Tumours Borderline for Resection
– non-treatable primary tumour;
– widespread pulmonary disease;
– locoregional recurrence;
– peritoneal disease
– extensive nodal disease, such as retroperitoneal, mediastinal or portal nodes; and
– bone or CNS metastases. (Category of evidence II; strength of recommendation
Tumours Borderline for Resection
• Those patients with tumours thought to be borderline for resection may have resectable or ablatable disease and should be referred for discussion with the regional hepatobiliary unit before chemotherapy. (Category of evidence III; strength of recommendation C)
• Resectability may be achieved by portal vein embolisation or two stage hepatectomy to increase hepatic functional reserve and also by combinations of surgery and ablation. (Category of evidence IV; strength of recommendation
Ablative Therapy
• The decision to offer ablative therapy to patients with hepatic metastases should be made by the regional hepatobiliary unit.
• Patients who are not candidates for resection should be considered for the CLOCC (chemotherapy + local ablation versus chemotherapy) trial.
• Entry into the CLOCC trial should be considered for patients with nine or less metastases (up to 4 cm) without extrahepatic disease (EORTC 40004).
• Patients who are not suitable for entry to the CLOCC trial may be considered for ablative therapy. (Category of evidence IV; strength of recommendation D)
Patients Not Suitable for Resection or Ablative Therapy
• Patients with advanced disease unsuitable for liver resection or ablative therapy should be referred to the clinical or medical oncologist with a special interest in colorectal cancer for further management and supportive care.(Category of evidence II; strength of recommendation
Synchronous Metastases
• Normally, colorectal cancer resection and liver resection would not be performed synchronously. However, management of accessible small metastases detected preoperatively should be discussed with the local liver centre for consideration of combined resection.
• Lesions discovered at operation should not be biopsied. (Category of evidence III; strength of recommendation C)
• Excision of small atypical lesions should not be considered without discussion with the regional hepatobiliary unit.
• Patients should be referred for consideration of liver resection after recovery from primary surgery.
• Patients with potentially resectable liver disease and who have undergone radical resection of the primary tumour should be considered for liver resection before consideration of chemotherapy.
• Patients with unfavourable primary pathology such as perforated primary tumour or extensive nodal involvement should be considered for adjuvant chemotherapy prior to 5 .
Histopathy
• The histopathology report of the resected liver specimen must include specific details which can be used to determine prognosis.
• These should include number, size, and location of metastases, resection margin clearance from tumour, capsular invasion, degree of differentiation, presence of necrosis, vascular and lymphatic invasion, and lymph node status if sampled. (Category of evidence II; strength of recommendation B)
Follow Up After Liver Resection
• Follow up would normally continue for five years according to local protocol using CT chest and liver and CEA. Follow up should be performed by the liver centre or the referring unit following an agreed protocol. Any abnormality should be referred back to the liver centre for consideration of re-resection or ablation. (Category of evidence III; strength of recommendation C)
• In patients who develop recurrence, it seems appropriate to consider such lesions in the same way as the initial hepatic metastases and offer re-resection or ablation to patients based on operative risk and likely survival. (Category of evidence III; strength of recommendation)
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