The majority of metastatic liver tumors cannot be resected because of bilobar involvement, location, size, and/or proximity to large vessels. Drs. McCarty and Kuhn succinctly summarize the existing literature on cryosurgery and its potential use in patients with unresectable liver tumors.
As the authors note, cryotherapy was initially used in the 19th century to ablate cervical and breast cancers. The development of sophisticated technology, safer equipment, insulated probes, and intraoperative ultrasound have regenerated enthusiasm for the use of this procedure in the treatment of liver cancer, and several nonrandomized studies yielding 5- and even 10-year data have reported minimal morbidity, acceptable mortality, and very low recurrence rates.[1-3] Until these results are validated by prospective, randomized trials, however, the medical community is unlikely to consider cryosurgery as a viable option for patients with advanced hepatic malignancy.
In my experience, as well as that of some of my colleagues experienced in cryosurgery, the majority of patients referred for evaluation have not responded to chemotherapy, and their disease is too advanced even for cryosurgical ablation. Patients are often told that once they develop liver metastases, no options exist other than chemotherapy or supportive care.
Which Patients Are Candidates?
Cryosurgery is not a substitute for conventional resection of isolated liver metastases in patients with unilobar involvement and no evidence of extrahepatic disease, but it is an excellent option for two groups of patients with hepatic malignancy. The first group consists of patients with metastatic neuroendocrine tumors, which are resistant to chemotherapy and high-dose somatostatin(Drug information on somatostatin). Cryosurgical cytoreduction, even in the setting of limited extrahepatic disease, can reduce the debilitating symptoms caused by the release of bioactive substances and, in some cases, may facilitate a response to postoperative chemotherapy.
A second group of candidates for cryosurgical ablation are patients with cirrhosis and portal hypertension who develop liver tumors. In our experience and that of other investigators, primary hepatocellular carcinoma in the setting of severe cirrhosis can be safely eradicated with cryosurgery.
We recently analyzed the results of cryosurgical ablation of hepatic metastases in 130 patients whose colorectal cancer was not amenable to conventional resection and was not responsive to preoperative chemotherapy. In patients with more than five lesions, a hepatic artery infusion pump was also placed to deliver intrahepatic adjuvant chemotherapy. Patients undergoing cryosurgery and adjuvant chemotherapy survived a median of 30.8 months after diagnosis of liver metastasis. Interestingly, patients with more than five lesions had a survival similar to that of patients with fewer lesions (unpublished data, December 1997), supporting the use of regional chemotherapy.
Randomized Trial Needed
It is time to conduct a randomized, prospective trial designed to answer the following questions:
How does cryosurgery compare with chemotherapy alone in patients with hepatic metastases from colorectal cancer?
What is the role of hepatic artery-directed chemotherapy before or after cryosurgery?
What are the maximum number and size of hepatic lesions that can be ablated?
Should all patients undergo preoperative staging with a positron emission tomographic (PET) or carcinoembryonic antigen (CEA) scan to evaluate possible sites of extrahepatic disease?
Should cryosurgery be performed laparoscopically?
Should all surgeons who perform cryosurgery be trained in both hepatobiliary surgery and ultrasound?
This multicenter trial should be conducted with strict adherence to staging as well as eligibility criteria. The results of this trial will define the role of cryosurgical ablation in patients with advanced hepatic malignancy and hopefully will expand our treatment options for these patients.