Locoregional therapy–immunotherapy combinations in unresectable liver cancer

Immune-checkpoint inhibitor-based regimens have changed systemic treatment for unresectable hepatocellular carcinoma (HCC). This review summarizes the biological rationale and clinical evidence for combining these drugs with locoregional therapies (LRTs), including transarterial chemoembolization (TACE), transarterial radioembolization (TARE) and external-beam radiotherapy. LRTs may promote antigen release and alter the tumour microenvironment, potentially enhancing immune responses.

The authors report that five phase III trials of TACE–ICI combinations showed improvements in progression-free survival and objective response rates. They describe TACE-based combinations as the most practice-relevant approach to date, while noting that an overall-survival benefit has not been established. Evidence for pairing ICIs with TARE or external-beam radiotherapy is described as early-phase or real-world, with potential relevance in selected patients, including those with portal-vein tumour thrombosis.

The review highlights challenges in selecting patients and sequencing treatments, assessing response, and interpreting survival outcomes amid crossover and subsequent therapies. It also questions whether conventional imaging criteria adequately capture responses to combined treatment. The authors call for future trials to assess meaningful overall-survival gains or use overall survival as a primary endpoint. These findings summarize a review, not new trial data; the described evidence does not establish an overall-survival benefit or justify a general change in practice.