Metastatic melanoma to the liver: A contemporary and comprehensive review of surgical, systemic, and regional therapeutic options

Abstract

Effective management of hepatic metastases from ocular and cutaneous melanoma remains a major therapeutic challenge. Treatment options include hepatic resection, hepatic intra-arterial (HIA) chemotherapy, chemoembolization, and hepatic perfusions. Evaluating the efficacy of these interventions is limited by the retrospective nature of most of the data, although controlled phase 3 studies are starting to emerge. Studies of hepatic resection are strongly suggestive of a survival benefit following surgery in selected patients. Effective systemic agents for metastatic cutaneous melanoma are available and supported by randomized controlled phase 3 trials. In contrast, no active systemic treatment has yet been identified for metastatic ocular melanoma. HIA and intravenous delivery of fotemustine have been compared in a randomized phase 3 trial in patients with unresectable metastases from melanoma, but no differences between the 2 approaches were observed. Hepatic arterial chemoembolization appears only to be moderately effective according to uncontrolled studies; targeting patients with less liver involvement may improve outcomes. A recent phase 3 study showed a significant improvement in hepatic progression-free survival with percutaneous hepatic perfusion compared with best alternative care in patients with metastatic melanoma; however, the overall survival analysis was confounded by crossover of control patients to active treatment. In conclusion, hepatic resection offers the possibility of long-term survival in carefully selected patients with liver-limited metastases from melanoma. In patients with unresectable cutaneous melanoma, effective systemic therapy is the best treatment option. For patients with unresectable ocular melanoma, regional treatments are likely to assume a greater role until effective systemic treatments are identified. Cancer 2014;120:781-9.

Chemosaturation with Percutaneous Hepatic Perfusion in Unresectable Hepatic Metastases

“…[1][2][3] Complete surgical resection might represent a curative option in patients with isolated hepatic metastases, but resection is not possible in most patients because of the number, location, or size of the hepatic metastases. Likewise, poor hepatic functional reserve limits standard therapeutic options such as resection.…”

“…[1][2][3] In persons with ocular melanoma, the sole site of metastatic disease in up to 50% of individuals is the liver after treatment of the primary cancer. 4 The rate of median survival in persons with hepatic metastases from ocular melanoma is less than 9 months.…”

“…7,8 For patients with unresectable liver-dominant disease, multiple strategies for liver-directed therapy have been developed, including hepatic artery chemoembolization, radioactive bead embolization, hepatic arterial infusion, isolated hepatic infusion, and chemosaturation with percutaneous hepatic perfusion. 3 In Europe, chemosaturation with percutaneous hepatic perfusion was commercially launched in 2012, and a second-generation, high-efficiency filter was approved for use in conjunction with a proprietary hepatic delivery system that same year. 3,9 However, the US Food and Drug Administration has not approved chemosaturation with percutaneous hepatic perfusion for use in the United States.…”

“…3 In Europe, chemosaturation with percutaneous hepatic perfusion was commercially launched in 2012, and a second-generation, high-efficiency filter was approved for use in conjunction with a proprietary hepatic delivery system that same year. 3,9 However, the US Food and Drug Administration has not approved chemosaturation with percutaneous hepatic perfusion for use in the United States.…”

“…3,9,10 The liver is isolated from the systemic circulation by a double-balloon catheter inserted through the femoral vein. Chemotherapy-infused blood is then diverted through the arterial catheter via an extracorporeal pump circulation and is then filtered and returned to the patient via venovenous bypass and the jugular vein.…”