Colorectal cancer is the fourth most common malignancy in the United States. In 1996, it is estimated that 55,000 deaths were attributable to colorectal cancer in the United States. The most common reason these patients die is due to the cancer spreading to the liver (called hepatic metastases). Surgical resection (or removal) is the treatment of choice for most patients whose cancer has metastasized to the liver. However, as few as 20 percent of patients with hepatic metastases are candidates for resection. Alternative therapies, including chemotherapy and tumor ablation, currently are being evaluated for patients who are not eligible for liver resection.

On this page:

• How Colorectal Cancer Spreads to the Liver
• Treatment
• Screening
• Who Undergoes Liver Resection
• Goals of Liver Resection
• Benefits of Liver Resection
• Other Treatments for Hepatic Metastasis
• Conclusion

How Colorectal Cancer Spreads to the Liver

In order to appropriately assess the efficacy of intervention in the treatment of hepatic metastases it is important to understand the natural history of this process. Metastases that are found at the same time as the original colon tumor, called synchronous metastases, are identified in approximately 20 percent of patients explored for a primary colon cancer. Metachronous metastases are identified after operation for the primary tumor but often represent undetected synchronous metastases especially when identified within six months of the primary diagnosis. The prognosis for a patient with hepatic metastases is most likely to be dependent on:

• the presence of tumors found outside the liver,
• the number of liver tumors, and
• the proportion of liver replaced by tumor.

Patients with hepatic metastases who do not have the tumors surgically removed have a survival rate of approximately 12 months and a three-year survival rate of less than five percent.

Treatment

Several studies have shown that liver resection (surgical removal of the tumor) is the most effective treatment currently available for patients with hepatic metastases. In order to maximize the benefits of surgical resection, it is critical for a physician or surgeon to rule out the presence of tumors/disease outside the liver. With few exceptions, patients who have extra hepatic disease do not benefit from surgical resection. The preoperative evaluation then becomes a critical factor in maximizing the benefit of liver resection in these patients.

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Screening

The best screening method for patients with colorectal cancer is controversial. Some physicians favor frequent, aggressive monitoring such as checking levels of an antigen specific to colorectal cancer (called CEA) and using CT scans to identify treatable local recurrence (in the colon) or distant metastases (outside the colon). With the early identification of hepatic metastases, some physicians have advocated for a waiting period of three to six months during which a physician monitors the patient for new metastatic disease. However, delaying surgery may make the resection more difficult due to tumor growth or may result in further spread from the liver metastasis.

Because it is clear that most patients with systemic metastases (cancer throughout the liver, not just in one area of the liver) should not undergo liver resection, all patients should have a careful pre-operative evaluation including a good quality chest x-ray and/or a chest CT scan. A single lung metastasis in the presence of liver metastases is not a contraindication to liver resection when lung resection is part of the treatment plan. A physician will administer an abdominopelvic CT scan to identify local recurrence or any new disease in the abdominal region. If a patient experiences bone pain, a physician can evaluate the patient for symptoms of metastatic disease. A whole body PET scan is a critical test in evaluating patients with colorectal metastases and is used with a CT scan as a screening test for persistent intra/extra-abdominal disease. A physician might also recommend a colonoscopy for patients who have not had their colons cleared within the past year.

A CT scan or magnetic resonance imaging (MRI) is essential to surgical planning. Both tests have similar specificity and sensitivity in identifying hepatic metastases and can detect tumors less than one centimeter. Important information that is gained from a detailed liver study includes the number and size of tumors, and their relationship to major vascular and biliary structures. These studies must be supplemented by intraoperative evaluation of the liver using ultrasound in order to identify otherwise undetected disease. The addition of intraoperative ultrasound improves the accuracy of liver evaluation to over 95 percent and may significantly alter the operation in up to 60 percent of patients.

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Who Undergoes Liver Resection

Each patient carries a complex combination of factors that dictate their candidacy for liver resection. Clear indications that a patient should not undergo liver resection include the presence of tumor outside the liver, including local lymph nodes, and resections that will not be complete. Lung metastases are typically a contraindication to liver resection, however there are reports of improved outcome with removal of both solitary lung and liver metastases. Such patients are rare but may be offered this combination intervention under the appropriate circumstances. Patients with tumors invading resectable structures (e.g. diaphragm or vena cava) should undergo en bloc resection (resection of all involved organs.)

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Goals of Liver Resection

The goals of liver resection are complete removal of all cancerous tissue or cells, and a minimum risk of morbidity and mortality. Historically, patients were considered to be candidates for liver resection if they had three or fewer tumors confined to one hepatic lobe. However, newer data indicate that the number of tumors may be less important than the completeness of resection. Based on these data, many medical centers performing liver resection for hepatic metastases have changed their criteria for resection from being limited by the number of tumors present to the ability to obtain complete resection with negative margins (no remaining disease).

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Benefits of Liver Resection

Liver resection offers the only opportunity for long-term survival for patients with isolated hepatic metastases. The five-year survival rates for patients undergoing liver resection runs between 20 percent and 40 percent, with the majority of these patients being disease-free at five years. The sources of failure include local and/or systemic recurrence. Patients whose liver disease recurs alone could undergo a second liver resection. These patients seem to fare as well as those who undergo the initial liver resection.

In order to reduce the incidence of recurrent disease, a number of researchers have studied the use of additional chemotherapy, either systemic or regional after liver resection. The use of additional, or adjuvant, systemic chemotherapy is becoming more widely used, although its true effect has not been proven in scientific studies. Click here for a list of current gastrointestinal clinical trials at the Masonic Cancer Center.

The mortality of elective liver resection has fallen from approximately 10 percent in the 1960s to less than five percent in the 1990s. Morbidity specific to liver resection includes bile leak, biliary injury, fluid in the chest, and less commonly, liver failure. The major and minor complication rate should be less than 30 percent. A blood transfusion, once common with liver surgery, now is necessary in fewer than 10 percent of patients. Patients undergoing liver resection by surgeons at the University of Minnesota Medical Center are typically cared for on the general surgical ward rather than the intensive care unit. The median length of hospital stay is six days.

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Other Treatments for Hepatic Metastasis

Because fewer than 20 percent of patients with hepatic metastases are candidates for surgical resection, a variety of other therapies have been used to treat the disease, including tumor ablation: cryosurgery and radiofrequency thermal ablation; and combination therapy.

Individually, none of these treatments has been proven to prolong patient survival. However, there is great interest and promise in the application of combination therapy in the management of this disease process.

Tumor Ablation: Cryosurgery and Radiofrequency Thermal Ablation

Ablation techniques to treat metastatic tumors in the liver has been used for more than 10 years throughout the world. Cryosurgery has been used more extensively than other types of tumor ablation techniques. During cryosurgery, a surgeon inserts a metallic probe (three to ten millimeters in diameter) into the center of a metastatic tumor, using ultrasound for guidance. Liquid nitrogen or argon is passed through the tip of the probe into the tumor, resulting in rapid freezing (-196 degrees Celsius) of the surrounding tissue. The formation of an ice ball results in osmotic and mechanical cellular injury and destroys cancer cells. The physician uses ultrasound to monitor the formation of the ice ball, which ideally forms up to a margin of one centimeter of normal tissue. The tumor is then thawed and re-frozen, thus increasing cell death. Cryosurgery is used on tumors up to eight centimeters, but treatment of these large tumors may be associated with an increased risk of complications.

Radiofrequency thermal ablation leads to frictional heat generation (80 — 100 degrees C), resulting in tissue death. The radiofrequency thermal ablation device is comprised of a needle through which an array of wires are exited. These wires monitor the progress of the ablation ball. Although the technology is changing, currently radiofrequency thermal ablation can be used on a tumor of five centimeters. Radiofrequency thermal ablation is performed under CT scan and ultrasound guidance, or in the operating room. Preliminary reports indicate that radiofrequency thermal ablation may be associated with fewer complications than cryosurgery, though no direct comparison has been made.

Available data indicate that either form of tumor ablation techniques result in satisfactory control (more than 90 percent) of the treated tumor(s). Because of a lack of randomized prospective studies, it is premature to assess the long-term survival benefit of ablative therapy or to compare its efficacy to that of liver resection. There is preliminary data that may indicate that tumor ablation therapy can lead to improved survival from complete tumor control in appropriately selected patients with unresectable hepatic metastases.

Combination Therapy

The most promising approach for treating patients with unresectable hepatic metastases is the combination of local tumor ablation with regional and/or systemic chemotherapy. This type of combination therapy uses the proven strengths of each form of therapy while covering for the weaknesses. The possible application of these ablative techniques by minimally invasive procedures also may minimize patient morbidity and hospitalization-associated costs. Preliminary studies using cryotherapy and hepatic artery infusion chemotherapy have demonstrated that this combination therapy is safe and has a promise for efficacy. Carefully designed, multi-center trials are needed to evaluate the effectiveness of using combination therapy to treat unresectable hepatic metastases. Click here for a list of current gastrointestinal clinical trials at the Masonic Cancer Center.

Conclusion

Hepatic metastasis is an important and highly morbid process commonly seen in patients with colorectal cancer. A careful algorithm for the follow-up and evaluation of patients with colorectal cancer will identify those patients with hepatic metastases who will benefit from liver resection. Whenever possible, patients with more extensive disease should be offered treatment as part of a protocol-based therapy or a randomized trial. Only through this form of clinical investigation will physicians be able to understand the role and efficacy of each new therapy in managing this difficult patient population.

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