Percutaneous Hepatic Perfusion for the Treatment of Hepatic Metastatic Uveal Melanoma: A Primer for Trainees

1. Describe the percutaneous hepatic perfusion (PHP) procedure, its indications, and data to support the use of PHP as a first line therapy for liver metastases from uveal melanoma (UM).

2. Understand the advantages and disadvantages of PHP compared with its surgical counterpart, isolated hepatic perfusion (IHP).

Background: Half of patients with UM develop metastases, 90% of which occur in the liver. Median survival of these patients is 6-12 months. Several treatments for UM liver metastases have been investigated, including systemic chemotherapy, immunotherapy, resection, and intra-arterial therapies, however efficacy has been limited. IHP is an invasive therapy and carries high morbidity/mortality. PHP with melphalan is a recently FDA-approved, minimally invasive treatment that delivers high concentrations of chemotherapy through hepatic circulation while isolating the liver from systemic circulation.

Clinical Findings/Procedure Details:

Indications for PHP include patients with unresectable hepatic metastases affecting less than 50% of the liver with no extrahepatic disease, or patients with extrahepatic spread amenable to resection or radiation. For the procedure, introducer sheaths are placed in the common femoral artery and common femoral vein and a venous return sheath is placed in the internal jugular vein. A microcatheter is positioned in the target hepatic artery for melphalan infusion. A double-balloon catheter is positioned in the IVC and used to isolate hepatic venous return. The melphalan-enriched venous return from the liver is pumped through fenestrations in the catheter and into an extracorporeal filtration system, removing melphalan before returning the blood to systemic circulation.

The FOCUS trial was a single-arm, multicenter phase 3 trial that assessed the efficacy of PHP for unresectable UM liver metastases. Objective response rate (36%), overall survival (20.5 months), and progression free survival (PFS) (9 months) were all favorable compared to other therapies. A recent retrospective analysis comparing first-line therapies including PHP, liver-directed, and immunotherapy found that hepatic PFS for was 17.6/8.8/9.2 months and overall PFS was 15.4/8.8/9.2 months, respectively.

Conclusion and/or Teaching Points:

PHP is an FDA-approved therapy for liver metastases from UM and should be considered as first-line therapy in patients with liver-dominant disease. PHP has demonstrated favorable progression free and overall survival compared with best alternative care.