Adjuvant Immunotherapy after Curative Treatment for Hepatocellular Carcinoma

Hepatectomy and radiofrequency ablation (RFA) have been established as curative therapies for hepatocellular carcinoma (HCC); however, HCC still has a high recurrence rate after these treatments. A study of HCC pathology has shown that microscopic intrahepatic metastasis occurs in about 10% of tumors ≤2 cm, and microvascular invasion occurs in about 27% of these tumors [1]. Thus, even small HCCs (≤2 cm) have a risk of recurrence. Moreover, intrahepatic metastasis is a major problem for tumors >2 cm because increasing tumor size past this cutoff is correlated with an increased risk of intrahepatic metastasis and microvascular invasion [2]. One reason why the prognosis of HCC is so poor is that patients experience repeated recurrences even after curative treatment, and repeated treatments with RFA, hepatectomy, and transarterial chemoembolization deteriorate liver function in many patients, ultimately resulting in death from liver failure or from tumors that are not amenable to treatment with systemic therapy. This suggests that preventing recurrence of HCC after curative treatment could dramatically improve the prognosis. Several studies on the prevention of recurrence have been conducted to date, but all have failed [3, 4, 5]. Consequently, there currently remains an unmet need for research on adjuvant therapy after curative treatment for HCC. The most prominent clinical studies of adjuvant therapy for recurrence prevention conducted to date investigated vitamin K [3], retinoids (the NIK-333 study) [4], and sorafenib (the STORM trial) [5]. However, the 1-year recurrence rates were high (25%, 34%, and 42%, respectively) in the control arms of all these studies. Another study showed a 5-year recurrence rate of about 80% after curative treatment for HCC. Recurrence after curative treatment can occur early or late. Early recurrence is primarily associated with intrahepatic metastasis, whereas late recurrence is often multicentric in origin [6].