What are the Usual Treatments? Management of Metastatic Liver Tumors from Other Sites
In the following sections, the available data regarding resection of liver metastases of a variety of non-colorectal, non-neuroendocrine, non-renal cell cancers will be reviewed: in short, however, the available data is difficult to interpret. Studies frequently represent retrospective reviews of a single institution's experience, rather than data derived from well-designed studies. Because of this, the information can be misleading and/or difficult to interpret and must be reviewed with this in mind.
Furthermore, the treatment recommendations for each of the following diseases are largely based on studies of resection (removal). Ablation techniques should be applied with the same indications as resection. The decision to apply one approach over another is based on the feasibility of resection, the ability to perform complete tumor ablation and other patient safety related issues.
Breast cancer
The role of surgical removal of liver metastases of breast cancer remains very controversial. Breast cancer has a significant propensity to spread to lungs, bones, and liver. Unfortunately, it is rare occurrence to identify a patient who has a surgically treatable liver metastasis from breast cancer without other evidence of other areas of spread. Also, in general, the detection of hepatic metastases of breast cancer portends a poor prognosis with the median survival of patients rarely exceeding two years. However, metastatic breast cancer can be a highly variable disease, and the overall statistics should not prevent an individual for pursuing further surgical therapy.
A number of groups have reported on the results of liver resection for isolated hepatic metastases of breast cancer. Surgical therapy of liver metastases of breast cancer was limited to those patients with isolated liver disease in these studies. Not all patients who underwent exploration for possible liver resection were resectable. Despite the best preoperative imaging studies, the identification of diffuse abdominal metastases and lymph node involvement oftentimes is identified at the time of operation. Under these circumstances liver resection should not undertaken.
The factors that favor a positive outcome from liver resection in breast cancer include - the liver being the first and only site of distant metastasis, the absence of tumor bearing lymph nodes around the liver (diseased portal lymph nodes) and curative resection (no tumor left in the liver). When these factors are present, liver resection resulted in a significant improvement in overall survival. One study from France reported a five-year survival of 60% in a retrospective analysis of 21 patients who underwent liver resection. Remember, these patients had a variant that is both in Stage IV breast cancer that probably behaves differently from patients with disease in and outside the liver.
Those patients who tend to benefit most from liver resection for metastatic breast cancer have the liver as the first and only site of metastasis. Patients with residual liver disease who have disease outside the liver regress while on systemic chemotherapy may also benefit from liver resection. Although patients with this pattern of disease will be rare, aggressive therapy is appropriate and should be pursued.
As part of a plan for liver resection in breast cancer you should consider the role of preoperative and/or postoperative chemotherapy. There is no good data to definitively direct therapy under these circumstances, but given the natural history of metastatic breast cancer (additional therapy should be considered). Discussions about therapy either before or after liver surgery should be made with a multidisciplinary care team prior to undertaking an operation since hepatectomy may be providing only a cytoreductive benefit (reduction in the amount of tumor in the body, rather then offering an opportunity for cure). In other words your surgeon may remove all gross tumor, but microscopic disease probably remains. So those patients with isolated liver disease may get an improved benefit from liver resection with additional systemic chemotherapy.
Reports of the administration of high doses of chemotherapy directly in the liver through the use of hepatic artery infusion pumps have also been reviewed. The benefit of such intervention is not clear. Recurrence of disease in the liver, even after aggressive therapy is not necessarily a cause of death. Local infusional chemotherapy should best be undertaken under a strict protocol. You must consider the risks of this form of therapy very carefully prior to undertaking such intervention.
Sarcoma (extremity, retroperitoneal, bowel)
Whenever possible, the general approach to the management of all forms of metastatic sarcoma involves resection and adjuvant chemotherapy. There are reports in the literature of repeat resection of patients with pulmonary (lung) metastases who have had prolongation of survival. The resection of liver metastases of soft-tissue sarcoma, however has not been associated with a prolongation survival, with most patients demonstrating recurrence in the liver.
In contrast to the treatment of the primary of sarcoma, once a metastatic lesion is identified in the liver histologic grade, primary tumor site, disease-free interval or an incomplete liver resection does not alter outcome.
It is clear that hepatic metastases of soft-tissue sarcomas do not typically respond well to conventional chemotherapy regimens. Therefore, in patients who can undergo a complete resection of all identifiable gross tumor, liver resection and additional chemotherapy may be warranted, especially in the context of a clinical protocol. Patients who have symptomatic hepatic metastasis sarcoma may be offered palliative therapy, such as chemoembolization, tumor resection/ablation in an attempt to control symptoms. It should be understood that patients with liver metastases of sarcoma do not have a favorable 5-year survival and unlike the approach of repeated resection taken for non-liver metastases, repeated resection for liver metastases is not supported in the literature.
Noncolorectal adenocarcinomas of the GI tract ( pancreas , stomach, small intestine)
A variety of centers have reported no benefit to the resection of liver metastases of noncolorectal gastrointestinal tract adenocarcinomas. The natural history after liver resection of these disease processes is for the re-appearance of tumor elsewhere in the liver, elsewhere in the abdomen or lungs. Several series have demonstrated no 5-year survivors after resection of noncolorectal GI metastases.
Liver resection may, however, be considered as part of a potentially curative initial operation for tumors (usually gastric) demonstrating direct invasion. Combined liver and pancreas resection (Whipple operation) should be considered in those patients with bile duct or gallbladder cancers in order to obtain negative margins.
Lung
Lung cancers (small cell or non-small cell) very rarely metastasize to the liver as an isolated, surgically treatable process. There is no data indicating that local treatment of such lesions will benefit long-term survival.
Ovarian Cancer
Gynecologic oncologists have long debated the role of tumor debulking (cytoreduction) in advanced (Stage IV) ovarian carcinoma. The basis for this debate comes from the apparent increased sensitivity of smaller volumes of ovarian cancer to chemotherapy. Cytoreduction can be accomplished by surgically removing/minimizing peritoneal nodules, the omentum and other sites of tumor deposits (including the liver).
Inadequate tumor debulking is clearly of no benefit, i.e. when significant residual disease remains after operation. A combined approach to the treatment of patients with hepatic metastases of ovarian cancer involves careful, detailed abdominal exploration, either laparoscopic or open, to evaluate for significant residual peritoneal or pelvic disease. If no significant extrahepatic residual disease remains, then intraoperative ultrasound is performed and the resection/ablation is planned. Only if a satisfactory, preferably complete, resection/ablation can be performed will the liver procedure be performed. In this selected group of patients a significant survival benefit has been demonstrated with a combination of surgery and additional chemotherapy.
Summary
There are several issues you should consider before proceeding with therapy of liver metastases from this group of diseases. First, a careful evaluation for disease outside the liver must be undertaken. If extrahepatic disease is identified, it is exceedingly unlikely that treating the liver will affect outcome. Certain diseases, especially noncolorectal GI tract adenocarcinomas, are also unlikely to be cured or significantly helped by controlling metastatic liver tumors. Additional therapy should be sought in the treatment of these diseases after liver resection/ablation. The optimal circumstance is to participate in a trial based out of a cooperative oncology research group, hospital or university. This approach will help insure the safest application of these new treatments. Clinical trials also allow researchers to determine the effectiveness and appropriate application of new therapies in these difficult and often rare diseases.
