# Immunotherapy in Hepatocellular Carcinoma with Portal Vein Tumour Thrombosis: From Poor Prognosis to Curative-Intent Strategies

## TL;DR

This paper reviews how immunotherapy, alone or combined with other treatments, can improve outcomes for patients with hepatocellular carcinoma and portal vein tumor thrombosis.

## Contribution

The paper highlights the potential of immunotherapy combinations to significantly improve survival and response rates in HCC patients with PVTT.

## Key findings

- Combination therapies achieve an 82% objective response rate and 97% disease control rate in PVTT-HCC patients.
- Quadruple therapy (HAIC-TACE plus targeted and immunotherapy) yields 12.9 months of progression-free survival.
- Immunotherapy modulates the tumor microenvironment and synergizes with other treatments to enhance antitumor efficacy.

## Abstract

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer-related mortality. One of the complications of HCC is malignant portal vein thrombosis. Portal vein tumour thrombosis (PVTT) is an aggressive form of cancer closely linked to reduced patient survival and with few treatment options. The introduction of immunotherapy has marked a paradigm shift in the management of HCC and it is precisely in this patient setting that it could play an important role in downstaging. This narrative review provides a comprehensive assessment of immunotherapy in patients with PVTT-HCC.

Background/Objectives. Globally, hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and represents the third leading cause of cancer-related mortality. Despite advances in diagnosis and treatment, the overall prognosis of HCC remains poor, largely due to late-stage presentation and high rates of vascular invasion. Portal vein thrombosis constitutes a significant complication of HCC, with an occurrence rate of 35–50%. Portal vein tumour thrombosis (PVTT) represents an aggressive form that is closely linked to decreased patient survival. The incidence of PVTT increases over time, from approximately 21% in the first year after diagnosis to nearly 46% by the third year, highlighting its high prevalence and progressive nature. The introduction of immunotherapy has marked a paradigm shift in the management of HCC. Immune checkpoint inhibitors, particularly those targeting the PD-1/PD-L1 and CTLA-4 pathways, have demonstrated durable responses and significant survival benefits in certain patients with advanced HCC. Furthermore, emerging evidence suggests that combining immunotherapy with local or systemic therapies, such as trans arterial chemoembolization, hepatic arterial infusion chemotherapy, radiotherapy or tyrosine kinase inhibitors, may further enhance antitumor efficacy by modulating the tumour microenvironment and promoting synergistic immune activation. Method: This narrative review provides a comprehensive evaluation of immunotherapy in patients with HCC and PVTT, with a focus on its efficacy as both monotherapy and in combination with other treatment modalities in terms of tumour response, progression-free survival, and overall survival. It also addresses safety, patient selection, and emerging strategies to optimize outcomes in this high-risk population. Conclusions: The combination of multiple therapies could improve the patient’s prognosis by achieving objective response rate of almost 82%, disease control rate of 97% and progression free survival of 12.9 months with quadruple therapy (HAIC-TACE combined with targeted and immunotherapy).