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Original Article |
Department of Surgery, Queens Cancer Center, Mt. Sinai School of Medicine, 8268 164th Street, Room A531, Jamaica, New York 11432
Correspondence: Address correspondence and reprint requests to: M. Margaret Kemeny, MD, FACS; E-mail: kemenym{at}nychhc.org
The patient is asymptomatic with synchronous hepatic metastases from a colorectal primary tumor. The options for treatment would be to resect the colorectal primary tumor and treat the liver metastases or to give chemotherapy first and then see if resection is feasible.
The ultimate goal of every cancer surgeon is to cure the patient. For the vast majority of patients with metastatic disease, this is impossible. In those situations, surgery must be used as a palliative tool; thus, extirpative surgery is generally not needed in the asymptomatic patient, especially with the advent of new chemotherapy agents that have such good response rates in patients with colorectal cancer. However, in the patient with synchronous liver metastases only, there remains a chance for cure, and that chance should always be pursued. New data about hepatic artery infusions in the face of unresectable liver metastases show extremely high response rates in the liver and make the chance of converting patients’ disease into resectable lesions a possible reality.1
Thus, in a patient who is capable of undergoing surgery and who has a primary colorectal cancer and liver metastases only, the best treatment would be a resection of the primary cancer and placement of a hepatic artery infusion pump for unresectable disease or resection of the liver metastases and placement of a hepatic artery infusion pump. Treatment with systemic chemotherapy before surgery would not help the situation and may allow potentially curable disease to become too large for resection.
Synchronous hepatic metastases from colorectal primary tumors occur in approximately 20% of patients with colorectal cancer.2 The question of operability of the hepatic lesions does not hinge on whether or not the metastases are synchronous. Because patients with synchronous disease can also have 5-year survivals of >25%, they should not be excluded from hepatic resection.2,3 The important factors for assessing whether colorectal metastases are resectable have been assessed by two groups with large retrospective studies.3,4 Both of these groups were addressing patients with metastases confined to the liver, and thus patients with portal lymph nodes involved with tumor, with carcinomatosis, or with lung or other organ metastases were not considered good candidates for hepatic resection. One of the systems was developed by Dr. Yuman Fong at Memorial Sloan-Kettering Cancer Center and included five clinical criteria.4 They were (1) the nodal status of the primary tumor, (2) the disease-free interval from the time of the primary operation to discovery of liver metastases (
12 or >12 months), (3) more than one tumor, (4) a preoperative carcinoembryonic antigen level >200 ng/mL, and (5) largest tumor >5 cm. Each negative criterion was assigned one point, and the 5-year survivals were calculated. For patients with a score of 0, the 5-year survival was 60%, compared with 14% for those with a score of 5. The authors noted that in actuality, no patient with all five negative criteria survived for 5 years. Patients with a score of 1 had a 44% survival.
Both of these scoring systems help us to evaluate patients before they go to surgery. The only information we have on this patient is that the metastases are synchronous. If that is the patient’s only negative factor, then the survival from resection is better than the possible survival with any other form of therapy, such as systemic chemotherapy, even with the best new agents.
Most large studies now show that liver resection can be performed with a low mortality rate: 4% or lower is acceptable, and the 5-year survival rate for patients with one to three liver metastases should be approximately 30%.2 Most patients with liver resections experience recurrence in the liver. Because of the high recurrence rate, two prospective randomized studies in the United States looked at hepatic artery infusion of floxuridine as a therapy after liver resection. One from Memorial Sloan-Kettering randomized patients to hepatic artery infusion and systemic therapy after liver resection versus only systemic chemotherapy.5,6 The second study was an intergroup study led by the Eastern Cooperative Oncology Group that compared hepatic artery infusion and systemic therapy versus no chemotherapy after hepatic resection.7 These studies were not powered for an end point of overall 5-year survival but, rather, 5-year disease-free survival. Both studies showed an increased disease-free survival for patients who received hepatic artery infusion and showed a marked decrease in recurrent hepatic metastases. Thus, if this patient has no extrahepatic metastases, has three or fewer lesions in the liver, and has tumors that can be resected, this would be the best course of treatment for the patient, followed by hepatic arterial infusion and systemic chemotherapy for 4 months.
The question of how to stage the two procedures, the colorectal resection and the liver resection, really depends on the location of the primary tumor and the size and position of the hepatic metastases. There are now several series that demonstrate the safety of combined liver and colon resections.8,9 If the hepatic resection is relatively confined and can be performed through a midline incision, then it can be performed simultaneously with the colorectal procedure. However, for more extensive liver resections and for rectosigmoid cancers, it is probably better to stage the operations by leaving 3 to 5 weeks between procedures and performing the colorectal stage first.
If the patient has unresectable disease confined to the liver, then a hepatic artery infusion pump should be placed. A recent report of hepatic artery infusion of fluorodeoxyuridine combined with systemic oxaliplatin in combination with irinotecan 11 or 5-fluorouracil and leucovorin showed a 90% objective response rate in the former and 87% in the latter. These high response rates were remarkable because 89% of the patients had been previously treated and all were considered to have unresectable disease. Moreover, one third of the patients treated with hepatic arterial infusion and combined oxaliplatin and camptothecin 11 went on to surgical liver resection.
So, in summary, this patient with synchronous liver-only metastases should have resection of the colorectal primary tumor and at the same time have a hepatic artery infusion pump placed if the disease is unresectable. If the hepatic disease is deemed resectable, it should be removed, either simultaneously or as a staged procedure. Then the patient should receive postoperative chemotherapy by using hepatic artery infusion as well as state-of-the-art systemic therapy, which would probably be a combination of oxaliplatin and 5-fluorouracil/leucovorin.
Received for publication July 27, 2005. Accepted for publication October 24, 2005.
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  G. Galizia, E. Lieto, M. Orditura, P. Castellano, V. Imperatore, M. Pinto, and A. Zamboli First-Line Chemotherapy vs Bowel Tumor Resection Plus Chemotherapy for Patients With Unresectable Synchronous Colorectal Hepatic Metastases Arch Surg, April 1, 2008; 143(4): 352 - 358. [Abstract] [Full Text] [PDF]
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