# Current Status of Multidisciplinary Treatment Strategies for Hepatocellular Carcinoma in the Era of Advanced Systemic Therapies

## TL;DR

This paper reviews how new systemic therapies are changing how hepatocellular carcinoma is treated, focusing on combining these therapies with curative local treatments.

## Contribution

The paper introduces and evaluates the oncological resectability criteria (R/BR1/BR2) as a framework for selecting surgical candidates in advanced hepatocellular carcinoma.

## Key findings

- Immune checkpoint inhibitors have expanded treatment options for hepatocellular carcinoma beyond traditional methods.
- The R/BR1/BR2 criteria provide a framework for assessing surgical candidacy but require further validation.
- Combining systemic therapy with locoregional treatments like TACE shows promise in enabling curative resection.

## Abstract

The therapeutic landscape of hepatocellular carcinoma (HCC) has been transformed by recent advancements in systemic therapies, particularly with the introduction of immune checkpoint inhibitors, expanding treatment options beyond conventional locoregional approaches. This review provides an overview of evidence accumulated from recent Phase III trials of first‐line regimens and key second‐line agents and examines how these advances enable multidisciplinary treatment strategies and timely transition to curative local treatments. We highlight prospective and retrospective data on systemic therapy administered in combination with or in sequence with locoregional treatment modalities, including TACE‐based combinations and “conversion” concepts leading to resection. A central focus is the oncological resectability criteria proposed by the Japan Liver Cancer Association and the Japanese Society of Hepato‐Biliary‐Pancreatic Surgery, which provide an objective framework to assess surgical indications under contemporary systemic therapy. Validation studies have consistently demonstrated robust prognostic stratification across resectable (R), borderline resectable 1 (BR1), and borderline resectable 2 (BR2) categories. Evidence for application of the oncological resectability criteria in treatment decision‐making is still insufficient. Thus, future prospective studies and real‐world registries aligned with the resectability framework are essential for defining the optimal timing, sequencing, and candidacy for surgery to ultimately enable provision of individualized, evidence‐based care for patients with advanced HCC.

Recent advances in immune checkpoint inhibitor‐based systemic therapies have transformed the treatment landscape of hepatocellular carcinoma, enabling multidisciplinary strategies that integrate systemic therapy with curative local treatments. This review summarizes the latest Phase III evidence and examines how emerging concepts—particularly the oncological resectability criteria (R/BR1/BR2)—provide an objective framework for selecting surgical candidates in the era of advanced systemic therapies. We also highlight current limitations and future directions, including the need for prospective validation and optimized timing and patient selection for surgery following systemic therapy.