Transarterial Therapy for Primary Liver Carcinomas: A Crack in the Armor?

Abstract

Primary liver carcinomas are a heterogeneous group of malignancies historically classified according to the cell of origin as hepatocellular carcinoma (HCC) or intrahepatic cholgangiocarcinoma (ICC). When localized to the liver, the optimal treatment for these tumors is surgical resection (or transplantation). Unfortunately, only the minority of patients with primary liver carcinomas are candidates for these potentially curative approaches due to extrahepatic metastases, coexisting liver disease, intrahepatic satellite nodules, or locally unresectable primary tumor. Patients who are not candidates for locoregional therapy often are treated with systemic therapy. Despite improvement in systemic therapy for both of these diseases, the response rates and overall survival for patients with primary liver carcinomas remain dismal. Two recent trials highlight the advances in systemic therapy for these diseases, and more importantly, emphasize the limitations of this approach. The SHARP Trial compared systemic sorafenib with placebo in 602 patients with advanced HCC. The trial was stopped prematurely due to the clear benefit for patients receiving sorafenib. The median overall survival time was 10.7 months in the sorafenib group compared with 7.9 months for the patients who received placebo. For patients with biliary tract cancers, the ABC-02 Trial demonstrated remarkably similar results. The median overall survival time was 11.7 months for patients treated with a combination of gemcitabine and cisplatin compared with 8.1 months for patients who received gemcitabine alone. Despite the benefit of these therapies in terms of the ultimate patient-important outcome of overall survival, it must be noted that in both of these trials, the actual tumor response rate was modest at best: 26.1 % of patients treated in the ABC-02 trial and only 2 % of the patients treated in the SHARP trial. These trials are clearly an important advance for medical oncologists, who now have therapies to offer patients with primary liver carcinomas that confer some benefit. Unfortunately, patients who have advanced primary liver tumors treated with systemic therapy still have little hope of long-term disease control and virtually no possibility of proceeding to curative-intent therapy. In this issue of the Annals of Surgical Oncology, Fowler and colleagues from Washington University report their experience managing 79 patients with biphenotypic primary liver carcinoma, a rare tumor with features of both HCC and ICC. The patients were treated with a variety of methods including liver transplantation (n = 6), resection (n = 27), hepatic arterial therapy (n = 18), and systemic therapy (n = 28). The overall report provides valuable information about the long-term prognosis of patients with this rare disease. The most compelling finding is the identification of hepatic arterial therapies as a potentially potent treatment method for primary liver malignancies. The patients were treated with one of three arterial therapies: transarterial chemoembolization (TACE, n = 6), transarterial radioembolization (TARE, n = 6), and hepatic artery infusional pump chemotherapy (HAIP, n = 6). As might be expected, the treatment selected for the patients varied based on the extent of disease. The patients selected for systemic therapy were far more likely to have distant metastases at diagnosis than the patients treated Society of Surgical Oncology 2015