Metastatic colorectal cancer to the liver develops in over 50,000 US patients each year and is rapidly fatal if untreated. Even the most active chemotherapeutic agents rarely prolong survival for more than 3 years. Liver
The article by Fong and Blumgart provides an overview of some of the surgical treatment options available to patients with liver metastases from colorectal cancer. Major liver resection, when performed in centers with extensive experience using modern surgical techniques, is a safe procedure, with mortality below 3%. Furthermore, blood transfusion is not required for the majority of patients undergoing liver resection at the University of Texas M. D. Anderson Cancer Center. In properly selected patients with colorectal cancer metastases confined to the liver, 5-year survival rates of up to 30% are achieved by complete resection of liver tumors. Thus, long-term survival is possible in selected patients following liver resection, although the majority of these patients do develop recurrent disease.
Screening Criteria for Liver Resection Candidates
The selection of patients likely to benefit from liver resection for colorectal cancer metastases is based on anatomic and biological considerations. Anatomically, there are two important concerns: (1) the resection must be performed with a tumor-free margin (preferably at least 1 cm) leaving (2) an adequate volume of functioning hepatic parenchyma with normal blood supply. Therefore, if a patient has a solitary liver metastasis in a location that precludes a margin-negative resection (such as the confluence of the portal veins or adjacent to the inferior vena cava at the entrance of the hepatic veins) or if complete resection would leave too small a volume of functional liver, resection with curative intent cannot be performed.
Biologically, patients who have extrahepatic disease or more than four liver metastases are at higher risk for developing further disease. Thus, most surgeons will not perform liver resection on patients with extrahepatic metastases (unless the only site of extrahepatic disease is a resectable anastomotic tumor recurrence), because the probability of long-term disease-free survival is extremely low.
While there is controversy regarding the number of liver metastases that should be considered a contraindication to liver resection, it is clear that patients with multiple metastatic foci in the liver usually have micrometastatic disease at other sites. Other biological factors, including a short disease-free interval or presence of synchronous liver metastases at the time of primary colorectal cancer diagnosis, may be associated with a decreased probability of long-term survival after liver resection. These factors, however, should not be considered absolute contraindications to proceeding with liver resection. Notably, the presence of bilobar metastases is not a contraindication to resection if the disease can be removed with negative margins and an adequate volume of normally perfused liver remains.
Controlling Disease Recurrence
Liver resection, as the only treatment for colorectal cancer liver metastases, achieves disease-free survival beyond 5 years only in a minority of patients. In patients in whom disease recurs, approximately half develop a recurrence in the liver and half at extrahepatic sites that include the lungs, lymph nodes, and peritoneal cavity. Thus, post-resection adjuvant therapy must be designed to treat micrometastatic disease at all of these sites. Our prior experience with a pilot program that administered a weekly dose of fluorouracil (5-FU) through a hepatic arterial port for 6 months after liver resection for colorectal cancer metastases suggested that the incidence of liver recurrence was reduced but recurrence at extrahepatic sites was not affected.
Because of findings like this, the liver surgery groups at Memorial Sloan-Kettering and M. D. Anderson are participating in clinical trials that combine regional and systemic chemotherapy in an effort to reduce the incidence of recurrence and improve long-term survival. These studies should include all colorectal cancer patients undergoing liver resection with curative intent, until such time as molecular and biological prognostic markers are developed that identify more accurately those patients at highest risk for recurrent disease.
The authors discuss the role of cryoablation in the treatment of patients with otherwise unresectable liver metastases. It is often possible to resect disease in one lobe and ablate one or two tumor nodules in the opposite lobe. This approach increases the number of patients who can be treated with curative intent. The few studies with long-term follow-up indicate that survival rates following cryoablation of liver metastases are similar to those achieved after liver resection. Cryoablation is, however, technically demanding, has local recurrence rates up to 20%, and is associated with significant morbidity in up to 40% of treated patients.
We are currently investigating a newer technique radiofrequency ablationto control unresectable primary and metastatic liver tumors. Radiofrequency ablation can be performed through a percutaneous or intraoperative approach. This technique achieves coagulative necrosis of hepatic tumors by passing an electrical current across monopolar or bipolar needle electrodes that are placed into the tumor using ultrasound guidance. Of the 123 patients with unresectable liver tumors that we treated with radiofrequency ablation, 3 developed complications (2.4% complication rate) and none died, whereas our experience with cryoablation led to a 2% mortality rate and a 39% morbidity rate.
With a median follow-up of 11 months, the local recurrence rate in tumors treated with radiofrequency ablation is 1.8%. As with cryoablation, some of the patients undergo resection in one lobe and radiofrequency ablation of tumor in the opposite lobe. Clearly, longer follow-up of patients who underwent radiofrequency ablation is needed to determine recurrence and survival rates.
Our expectation is that radiofrequency ablation of colorectal cancer liver metastases will produce long-term survival rates similar to those achieved with liver resection or cryoablation, but with a significantly lower complication rate than cryoablation. We believe that this technique will increase the number of patients with liver-only metastases who will be candidates for complete ablation of all measurable disease.
We are now embarking on a new clinical study that will combine radiofrequency ablation of colorectal cancer liver metastases with adjuvant regional and systemic chemotherapy, again in an attempt to reduce recurrence rates and improve overall survival. These aggressive multidisciplinary trials that combine surgical resection or ablation of colorectal cancer liver metastases with adjuvant chemotherapy provide our patients with the best opportunity for prolonged survival.
1. Curley SA, Roh MS, Chase JL, et al: Adjuvant hepatic arterial infusion chemotherapy after curative resection of colorectal liver metastases. Am J Surg 166:743-748, 1993.
2. Gagne DJ, Roh MS: Cryosurgery for hepatic malignancies, in Curley SA (ed): Liver Cancer, pp 173-200. New York, Springer Verlag, 1998.
3. Curley SA, Izzo F, Delrio P, et al: Radiofrequency ablation of unresectable primary and metastatic hepatic malignancies: Results in 123 patients. Ann Surg, 1998 (in press).