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EDITORIALS |
From the Division of Surgical Oncology, John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, California.
Correspondence: Address correspondence to: Anton J. Bilchik, MD, PhD, FACS, John Wayne Cancer Institute, 2200 Santa Monica Boulevard, Santa Monica, CA 90404; Fax: 310-449-5261; E-mail: bilchika{at}jwci.org
Hepatic metastases often present a therapeutic dilemma for the oncologist because of their significant morbidity and mortality. Most patients are treated with chemotherapy, frequently with disappointing results. Complete surgical resection is the only proven curative option, but most hepatic malignancies are considered unresectable because of unfavorable tumor location, decreased functional hepatic reserve, or poor patient performance.1 Radiofrequency ablation (RFA) was developed to eradicate tumors in unresectable locations and preserve uninvolved hepatic parenchyma in patients with diminished hepatic reserve. The versatility and low cost of RFA have generated considerable enthusiasm among surgeons and interventional radiologists. Surgeons can perform RFA in the operating room via laparotomy or laparoscopy; interventional radiologists can perform RFA in the radiology suite via a percutaneous approach guided by ultrasonography or computed tomography.2,3
Despite many retrospective studies that report low recurrence rates and safety of RFA,4,5 there is a paucity of long-term follow-up and overall survival data. In contrast, numerous studies have reported improved overall survival after hepatic resection.6,7 Currently, no randomized studies have compared RFA and resection. The single-arm studies reporting outcomes following RFA do not provide details regarding adjuvant therapy, which further complicates their analysis.
Although RFA is typically used for unresectable tumors, the definition of what is resectable can vary among institutions and individual surgeons. Many hepatic surgeons argue that a lesion that can be ablated is likely to be resectable and, if it is unresectable, then RFA is unlikely to improve survival. Nevertheless, numerous studies report low recurrence rates after RFA for hepatic lesions smaller than 3 cm.3–5 Additionally, RFA can significantly reduce cost and morbidity compared with resection.8
In this issue of Annals of Surgical Oncology, Dr. Elias et al. compare rates of local recurrence and disease-free survival in 88 patients whose hepatic metastases were managed by a combination of anatomic resection, wedge resection, and RFA.9 At a median follow-up of 27.6 months, the local recurrence rate was 6% after RFA, 7.3% after wedge resection, and 12.5% after anatomic resection. Although most hepatic metastases were from colon cancer, eight other types of malignancies were included. Patients with extrahepatic disease were not excluded. Local recurrence rates after RFA were significantly higher when metastases were larger than 3 cm or in close proximity to large blood vessels. The authors suggest that RFA is as effective as wedge resection for metastases smaller than 3 cm and results in fewer complications.
This study, however, suffers from many of the pitfalls previously described: a variety of tumor histologies are examined, limited information regarding systemic chemotherapy is provided, and three different radiofrequency probes were used. The use of different probes increases the risk of incomplete or inconsistent ablations. In addition, local recurrence rates after resection are higher than rates reported in other series.10 Ablation of central and bilobar lesions that may not have been resectable clearly increased the number of patients whose hepatic disease could be completely treated in the operating room. The local recurrence rate of only 6% after RFA can be partially attributed to the use of intraoperative ultrasound, which some studies suggest provides more accurate staging and monitoring of RFA.11 The inclusion of patients with extrahepatic disease did not appear to have a major impact on local recurrence rates. This suggests that more effective adjuvant regimens were used and that the combination of treatments is more effective than local therapy alone.
With numerous new chemotherapeutic and targeted agents available, the possible synergistic effect of debulking needs to be reexamined. Most studies that reported no survival benefit for resection of hepatic colorectal metastases in patients with extrahepatic disease were done in the era of single-agent (5-fluorouracil) chemotherapy,12 which was associated with response rates of only 15% to 20%.13 In the last decade, two additional agents, irinotecan and oxaliplatin, were found to be extremely effective against advanced colorectal cancer; these agents are associated with response rates of 39% to 51% and a significant increase in median survival.14 This year the US Food and Drug Administration approved two angiogenesis inhibitors, bevacizumab (Avastin) and cetuximab (Erbitux), which increase survival when given in combination with standard chemotherapy drugs. The effect of these agents after surgical debulking has not been addressed, but it is plausible that their use might further prolong survival, even in patients with limited extrahepatic disease.
The increasing number of effective therapeutic options for patients with hepatic metastases mandates a close collaboration between surgical and medical oncologists. All cases should be presented at a multidisciplinary conference, and clinical trials should be encouraged. This type of comprehensive management will eventually transform liver metastasis from an invariably fatal condition to one of manageable chronicity. The question is not whether metastatic hepatic malignancies should be resected or ablated, but how we should time and combine therapeutic interventions.
Received for publication March 12, 2004. Accepted for publication March 15, 2004.
REFERENCES
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