Management of Colorectal Liver Metastasis

Introduction

The liver is the most common site for colorectal cancer (CRC) metastases; 15% to 20% of patients present with synchronous lesions, and metachronous metastases occur in 40% to 50% of patients. Liver metastases are present in 60% to 70% of all patients who die of colorectal cancer. However, management of colorectal liver metastases (CRLM) has changed a lot during the past decade, and overall survival after liver surgery for colorectal metastatic disease has more than doubled. Resection is currently the gold standard of treatment, with 5-year overall survival rates ranging from 27% to 52%, but only 15% to 20% of liver metastases are considered resectable at the time of diagnosis. Patients with untreated CLRM have a median survival of 5 to 12 months.

Diagnosis and Preoperative Workup

Workup begins with a focused history and physical examination to assess the patient’s general functional status, medical comorbidities, and symptoms from the primary colorectal lesion such as obstruction, perforation, or bleeding. Patients with symptoms from the primary tumor typically undergo treatment. Staging studies should be performed before surgery. Laboratory tests are performed, including a baseline carcinoembryonic antigen (CEA) level.

Staging and Prognosis

The following staging system for metastatic disease was proposed by European Colorectal Metastases Treatment Group in 2007:

• M0: No metastases

• M1a: Resectable liver metastases

• M1b: Potentially resectable liver metastases

• M1c: Liver metastases that are unlikely to be resectable

Poor prognostic factors for liver resection include more than four liver tumors, poorly differentiated tumor, bilobar lesions, bulky lesions, hilar/celiac lymph nodes, inoperability of the primary tumor, local recurrence, lung metastases, other extrahepatic metastases, age older than 70 years, and cardiovascular/respiratory disease. The presence of portal nodal metastasis has been consistently associated with poorer prognosis, particularly when the hepatic artery group of nodes is involved. These patients appear to benefit most from multimodality treatment, including chemotherapy followed by surgical resection. When tumors are discovered intraoperatively, tumor response to chemotherapy has been used to guide further resection.

Postoperatively, infectious complications are associated with decreased overall survival. Bilobar disease, more than eight tumors, more extensive treatment than a hemihepatectomy, and R1 margin status have been associated with increased postoperative complications.

Prognostic Scores

Over the years, the following scoring systems have been proposed to help with risk stratification and patient selection for liver resection:

• Fong et al—scoring system (1999)

• Iwatsuki et al (Pittsburgh risk score, 1999)

• Nagashima et al—scoring system (2006)

• Zakaria et al (2007)

• Rees et al (2008)

These scoring systems were analyzed by Gregoire et al in 2010, who concluded that no single prognostic factor was common for all the scores. However, the most common factors included the number and size of the largest metastases, the disease-free interval between diagnosis of the primary cancer and development of liver metastases, CEA level, a stage III primary cancer, and presence of extrahepatic disease. It has become clear that generalized criteria may not be appropriate for every patient and that a more individualized approach is warranted.

Treatment

Initial treatment of a patient presenting with CRLM depends on his or her presentation. A useful starting point is to determine if the patient has symptoms relating to the primary tumor. In patients with signs and symptoms suggestive of hemorrhage, perforation, or obstruction, initial treatment should be resection or palliation of the primary tumor. In an asymptomatic patient, the initial treatment should be discussed by a multidisciplinary tumor board.