Therapeutic Treatment of Hepatic Colorectal Metastases

US Oncological Disease, 2007;1(2):88-91

In the US, colorectal cancer is the second most common cause of cancerrelated mortality. Unfortunately, about 35–55% of patients with colorectal cancer develop hepatic colorectal metastases. At present, surgical resection of these lesions represents the main therapeutic option and is the only chance for cure and long-term survival. In patients with extensive metastatic disease who are not candidates for resection only, radiofrequency ablation (RFA) can be combined with hepatectomy. While the principal goal of hepatic resection is to resect all metastases with negative histological margins, preservation of adequate liver parenchyma must be considered. The utilization of portal vein embolization (PVE) and neoadjuvant chemotherapy may lead to increased candidacy for surgical treatment of such colorectal metastases. Although a fraction of patients develop recurrent disease after hepatic resection, newer and more biologically active chemotherapeutic agents are available that may prolong both disease-free and overall survival. The current therapeutic options for hepatic colorectal metastases necessitate a multidisciplinary approach that involves surgeons, oncologists, and radiologists in order to increase the number of patients who are candidates for the surgical treatment of colorectal cancer liver metastasis.

In the US, there are approximately 150,000 new cases of colorectal cancer annually, accounting for more than 55,000 cancer-related deaths.1 Approximately 50% of these patients will develop hepatic colorectal metastases.2 Of these patients, 15–25% present with synchronous hepatic lesions,3–5 while another 20–25% will develop metachronous liver disease.6–8 Furthermore, in one-fifth of these patients the liver is the only site of metastatic disease.9 As a result, there are approximately 10,000–15,000 patients each year who are candidates for surgical resection of their hepatic colorectal metastases.8 Surgical resection of hepatic metastases remains the only therapeutic option with the potential for long-term cure.10 Long-term survival and potential cure following surgical resection for hepatic colorectal metastases have been demonstrated in numerous studies. The overall five-year survival rate reported after hepatectomy with curative intent ranges from 35 to 58%.10–19 These results are expected to improve even further with a multidisciplinary approach that includes newer chemotherapy regimens.20 As such, resection of colorectal liver metastasis should be considered standard practice. Furthermore, many traditional factors that were previously considered absolute contraindications to hepatic resection have recently been called into question. For example, even very well selected patients with extrahepatic metastatic disease may now be considered potential candidates for hepatic resection.21,22 Herein, we review the issues relating to the therapeutic management of patients with colorectal liver metastases.

Pre-operative Evaluation
Peri-operative mortality following hepatectomy has decreased from 20% pre-1980 to less than 5% post-1980.23–29 A key component in decreasing the risk of post-operative complications is the appropriate selection of surgical candidates. Several factors must be considered in the decision to offer major liver resection as a surgical therapy. Comorbidites and age are both factors, although age itself is not an independent predictor of increased operative risk.30,31 Surrogate markers of general physiological fitness, such as the American Society of Anesthesiology (ASA) score and thepre-operative acute physiology and chronic health evaluation (APACHE) score, are better indicators of post-operative complications risk.31,32 The goal of the pre-operative evaluation should therefore be to identify thosepatients who are at a high operative risk such that their comorbidities can be appropriately addressed in the pre-operative setting, thus reducing the risk of post-operative complications.

Every patient being considered for resection of hepatic colorectal metastases should have cross-sectional imaging performed to evaluate the extent of intrahepatic disease and to exclude extrahepatic metastasis. In general, pre-operative computed tomography (CT) is the imaging modality of choice, although some centers favor magnetic resonance imaging (MRI) to evaluate liver-based disease. Pre-operative imaging should be used to define the number of liver lesions and their distribution, as well as their proximity to major biliary and vascular structures. The lungs should also be evaluated pre-operatively with either a chest radiograph or a chest CT to rule out pulmonary metastasis.33,34 A mandatory colonoscopy within one year is also required to exclude either anastomotic recurrence or a metachronous colorectal tumor. More recently, positron emission tomography (PET) with the radiolabelled glucose analog [18F] fluoro-2- deoxy-D-glucose (FDG) has been used as a sensitive diagnostic tool to image tumors based on increased uptake of glucose by tumor cells. Retrospective studies have suggested that the ability of FDG-PET to detect extrahepatic disease may improve patient selection for surgery and thereby result in better survival rates following resection.35 Furthermore, PET has recently been combined with CT (PET/CT) in an attempt to improve identification of extra- and intrahepatic lesions.36,37 Data suggest that PET/CT provides the most accurate pre-operative imaging for staging purposes. As a result, some investigators36 advocate that PET/CT scans be routinely performed on all patients being evaluated for liver resection for metastatic colorectal cancer. Traditionally, liver resection for colorectal metastases was deemed inappropriate in patients who had any one of a strict group of criteria, including: four or more metastatic lesions, hilar adenopathy, metastases within 1cm of major vessels (i.e. inferior vena cava or main hepatic veins), or any evidence of extrahepatic disease. The clinical and methodological basis of these studies has been criticized over the years. Methodologically, many of these studies failed to control for many factors and patient selection was varied and non-standardized. Clinically, the data are problematic because many of the studies were conducted prior to the utilization of more effective, new-era chemotherapy agents. In addition, many of these studies were carried out before the introduction and widespread use of techniques such as RFA or PVE. More recent studies have suggested that patients with ‘traditional’ adverse clinicopathological factors can achieve long-term survival following hepatic resection and, therefore, should not be excluded from surgical consideration. This has led to a shift in the definition of the resectability of hepatic liver metastases. Newer criteria rely more on whether macroscopically complete (R1) and microscopically complete (R0) resection of the liver lesions can be performed. Hepatic colorectal metastases should be defined as resectable when it is anticipated that disease can be completely resected (i.e. R0 resection), two adjacent liver segments can be spared, adequate vascular inflow and outflow and biliary drainage can be preserved, and the volume of the liver remaining after resection (i.e. the ‘future liver remnant’) will be adequate (in general, at least 20–30% of the total estimated liver volume).38,39 This new definition of resectability represents a clear paradigm shift. Rather than resectability being defined by what is removed,decisions regarding resectability now focus on what will remain.

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