Less Is More: A Single-Dose, Non-Waiting Neoadjuvant Immunotherapy Strategy for Hepatocellular Carcinoma.

Area of Science:

• Oncology
• Immunotherapy
• Surgical Oncology

Background:

• Neoadjuvant immune checkpoint inhibitors (ICIs) are explored for solid tumors, but present challenges in hepatocellular carcinoma (HCC).
• HCC patients, especially those with large tumors, benefit from neoadjuvant immunotherapy but have narrow surgical windows.
• Prolonged neoadjuvant therapy can lead to disease progression, hinder resectability, and cause delays due to adverse events like hepatotoxicity.

Purpose of the Study:

• To propose a HCC-specific neoadjuvant immunotherapy approach prioritizing surgical feasibility.
• To investigate a single-dose, non-waiting strategy using anti-PD-1 or anti-PD-L1 antibodies shortly before surgery.
• To minimize treatment-related adverse events (TRAEs) and logistical complexity while preserving immunotherapy benefits.

Main Methods:

• Leveraging pharmacodynamic and clinical evidence on rapid receptor occupancy and T-cell activation with single ICI doses.
• Administering a single dose of anti-PD-1 or anti-PD-L1 shortly before surgical resection.
• Focusing on early antitumor immune activation without delaying the surgical window.

Main Results:

• Single ICI doses rapidly achieve near-complete receptor occupancy and sustained T-cell activation.
• This approach allows early immune activation while minimizing TRAEs and preserving surgical feasibility.
• Potential for reduced logistical complexity and enhanced patient/surgeon acceptance.

Conclusions:

• A single-dose, non-waiting neoadjuvant immunotherapy strategy is a viable option for HCC.
• This abbreviated approach may translate immunologic activation into clinical benefit, measured by event-free survival.
• Future HCC trials should explore this "less is more" paradigm for neoadjuvant immunotherapy.