HCC Treatment Trials: Expert Consensus Redefines How Systemic Therapy Should Be Studied With Surgery and Locoregional Treatment: JHEP | October 2026

What Does the Consensus Recommend?

An international multidisciplinary panel developed 18 consensus statements—nine addressing neoadjuvant/perioperative systemic therapy and nine addressing systemic therapy combined with locoregional treatment.

• Prioritize high-risk HCC: Neoadjuvant and perioperative trials should preferentially enroll patients at greatest risk of recurrence after curative-intent treatment.
• Use meaningful survival endpoints: The recommended primary endpoint for perioperative trials is 2-year event-free survival, analyzed using restricted mean survival time.
• Balance treatment duration with surgical safety: Systemic therapy must not compromise resectability, procedural safety or timely definitive treatment.
• Avoid heterogeneous trial populations: Combination trials should enroll clearly defined populations to improve interpretation and applicability.
• Choose clinically appropriate comparators: Control arms should reflect current standards rather than outdated or less effective treatment strategies.
• Systemic therapy is the preferred comparator for patients with larger tumor burden or locally advanced HCC undergoing combination-treatment trials.
• Assess both disease control and survival: Combination trials should evaluate progression-free survival and overall survival, using an alpha-recycling statistical strategy.
• Include clinically meaningful secondary endpoints: These are essential for understanding safety, treatment feasibility and eventual clinical applicability.
• Multidisciplinary trial design is essential: Hepatologists, oncologists, transplant surgeons, hepatobiliary surgeons and interventional radiologists must collaborate.

Why Does It Matter?

As immunotherapy and targeted treatments move into earlier HCC stages, the critical question is no longer simply whether adding systemic therapy improves tumor response, but whether it produces durable clinical benefit without compromising potentially curative interventions.

GastroAGI Takeaway

The future of HCC treatment is multimodal—but stronger trial design must establish which combinations genuinely improve survival.

This consensus establishes a framework for studying perioperative systemic therapy and systemic–locoregional combinations, emphasizing appropriate patient selection, contemporary comparators and clinically meaningful endpoints.