PSMA PET for the Staging and Management of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a leading cause of cancer-related mortality worldwide. Accurate diagnosis, staging, and treatment response assessment are critical for optimal management of patients with HCC. However, conventional imaging modalities, such as contrast-enhanced CT and MRI, have limitations in characterizing indeterminate liver lesions and in detecting intrahepatic or extrahepatic disease, particularly in the context of post-treatment changes.

This prospective, single-center study investigates the added value of F18-Piflufolastat (PSMA) PET/CT in the evaluation and management of patients with suspected or confirmed HCC. PSMA (Prostate-Specific Membrane Antigen) is a cell surface protein that, while originally characterized in prostate cancer, has demonstrated overexpression in the neovasculature of a variety of solid tumors, including HCC. F18-Piflufolastat is a radiotracer that targets PSMA, allowing for enhanced molecular imaging.

Participants will undergo PSMA PET/CT imaging in addition to standard-of-care imaging (CT and/or MRI). The study is designed to address three primary clinical questions:

1. Diagnosis: Does the addition of PSMA PET/CT improve characterization of indeterminate liver lesions (e.g., LI-RADS 3 or 4)? 2. Staging: Can PSMA PET/CT improve the accuracy of disease staging in treatment-naïve patients by detecting intrahepatic or extrahepatic disease not visualized on conventional imaging? 3. Treatment Response: In patients who have undergone locoregional therapy (LRT), does PSMA PET/CT provide more precise assessment of viable tumor tissue compared to standard imaging? Data collected will include imaging results, histopathological confirmation when available, changes in clinical management prompted by PSMA PET/CT findings, and correlation with clinical outcomes. By evaluating the clinical utility of PSMA PET/CT across multiple phases of the disease course, this study aims to inform future diagnostic algorithms and treatment planning strategies in patients with HCC.

• 1: Change in Clinical Management Based on PSMA PET/CT Findings; 2: Change in Clinical Staging in Treatment-Naïve Patients; 3: Change in Assessment of Treatment Response Following Locoregional Therapy [Time frame: 1: Within 30 days of PET/CT imaging; 2: Within 30 days of PET/CT imaging; 3: Within 30 days of post-treatment imaging]