Redefining Intermediate-Stage HCC Treatment in the Era of Immune Therapies

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. At diagnosis, most patients are ineligible for curative surgery, and approximately 20% of patients are diagnosed with advanced-stage disease. A significant proportion of patients fall under an unresectable or intermediate-stage disease who have liver-limited disease but are not surgical candidates because of large tumor size, number of lesions, or technically inoperable disease. In this unique intermediate-stage patient population, locoregional therapies have been the de facto mainstay of treatment because of high local response rates and favorable safety profile, especially in the context of minimally effective systemic therapies. However, not all patients who receive locoregional therapy for incurable disease have improved survival, and importantly, some of these patients never receive systemic therapy because of disease progression or further decline in hepatic function. Meanwhile, with the remarkable progress that has been made with systemic therapy in the past few years, revisiting the treatment of intermediate-stage HCC seems prudent. In this review, we will highlight current and emerging strategies for treating patients with unresectable, liver-limited HCC.