PSMA PET for the Staging and Management of Hepatocellular Carcinoma

Addition of F18-Piflufolastat PET/CT to Cross-Sectional Imaging for the Staging and Management of Hepatocellular Carcinoma

This prospective, single-center study evaluates the clinical utility of F18-Piflufolastat (PSMA) PET/CT when added to conventional cross-sectional imaging for patients with suspected or confirmed hepatocellular carcinoma (HCC). The study aims to determine whether PSMA PET/CT improves diagnostic accuracy for indeterminate liver lesions (LI-RADS 3 and 4), enhances staging precision in treatment-naïve patients, and provides more accurate assessment of treatment response in patients undergoing locoregional therapy (LRT). The goal is to assess how PSMA PET/CT may impact clinical decision-making, staging, and management of HCC across multiple stages of disease.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma (HCC)

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 90

Contacts and Locations

• Study Contact: Name: Binu V John, MD MPH; Phone Number: 17647 (305) 575-7000; Email: binu.john@va.gov
• Study Contact Backup: Name: Flavia R Carneiro, PhD; Phone Number: (305) 575-7762; Email: flavia.carneiro@va.gov

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33125
      • Recruiting
      • Miami VA Healthcare System, Miami, FL
      • Contact: Flavia R Carneiro, PhD; Phone Number: (305) 575-7762; Email: flavia.carneiro@va.gov
      • Contact: Binu V John, MD MPH; Phone Number: 17647 305-575-7000; Email: binu.john@va.gov
      • Principal Investigator: Binu V John, MD MPH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

This study will recruit 90 Veterans from the VHA with HCC, and no non-Veteran participants. This will include 30 participants with LR-3 and 4 lesions detected during surveillance (Aim 1), 30 treatment naïve participants towards Aim 2, and 30 treatment experienced participants for Aim 3. In addition, 10 participants out of the 60 who are recruited for aims 2 and 3 are projected to have indeterminate nodules, increasing the number of participants with indeterminate nodules to 40. West Palm Beach and Orlando VA patients who are evaluated at the Miami VA, will be approached for study recruitment. These Veterans will continue to be co-managed by the Miami VA and the local VA teams after undergoing treatment in Miami.

Description

Inclusion Criteria:

• Adult patients age >18 years from the VA medical system
• Treatment-naïve patients with HCC with BCLC B or C disease

Exclusion Criteria:

• Patients with renal dysfunction or contrast allergy that precludes contrast enhanced cross sectional imaging
• Patients with presence of active primary malignancy other than HCC and non-melanoma skin cancer in the past 3 years

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Indeterminate Lesions Cohort (Diagnosis Focus); Participants in this cohort have liver lesions categorized as LI-RADS 3 or 4 based on standard imaging. The purpose of the PSMA PET/CT is to assist in the further characterization of these indeterminate nodules and support diagnosis of HCC or benign pathology.
Treatment-Naïve Cohort (Staging Focus); This cohort includes participants with newly diagnosed HCC who have not yet received any locoregional or systemic therapy. PSMA PET/CT is performed to evaluate the extent of disease and detect potential intrahepatic or extrahepatic spread, contributing to improved staging accuracy.
Post-Treatment Cohort (Treatment Response Focus); Participants in this cohort have previously undergone locoregional therapy (e.g., TACE, RFA, or ablation). PSMA PET/CT is used to assess residual or recurrent disease and help evaluate treatment response compared to standard imaging.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1: Change in Diagnostic Classification of Indeterminate Lesions (LI-RADS 3/4) After PSMA PET/CT; 2: Change in Clinical Staging in Treatment-Naïve Patients; 3: Change in Assessment of Treatment Response Following Locoregional Therapy	Proportion of patients with LI-RADS 3/4 lesions whose diagnostic classification is revised (i.e., confirmed as HCC or benign) based on F18-Piflufolastat PET/CT findings, as compared to standard imaging alone. Final diagnosis will be based on histopathology (if available) or multidisciplinary tumor board consensus;; Number and percentage of treatment-naïve patients whose disease stage is upstaged or down-staged after PSMA PET/CT imaging, relative to standard imaging, according to modified BCLC or AJCC staging guidelines;; Difference in tumor viability classification based on PSMA PET/CT vs. standard imaging using mRECIST or LI-RADS treatment response criteria. Correlation with histopathologic or clinical follow-up will be evaluated where available.	1: Within 30 days of PET/CT imaging; 2: Within 30 days of PET/CT imaging; 3: Within 30 days of post-treatment imaging

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Proportion of patients with LI-RADS 3/4 lesions whose diagnostic classification is revised (i.e., confirmed as HCC or benign) based on F18-Piflufolastat PET/CT findings, as compared to standard imaging alone. Final diagnosis will be based on histopathology (if available) or multidisciplinary tumor board consensus;; Number and percentage of treatment-naïve patients whose disease stage is upstaged or downstaged after PSMA PET/CT imaging, relative to standard imaging, according to modified BCLC or AJCC staging guidelines;; Difference in tumor viability classification based on PSMA PET/CT vs. standard imaging using mRECIST or LI-RADS treatment response criteria. Correlation with histopathologic or clinical follow-up will be evaluated where available.	1: Within 30 days of PET/CT imaging; 2: Within 30 days of PET/CT imaging; 3: Within 30 days of post-treatment imaging

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
1: Inter-reader Agreement on PSMA PET/CT Interpretation; 2: Correlation Between PSMA Uptake and Histopathologic Features	Agreement between independent nuclear medicine readers on lesion characterization and treatment response using standardized reporting criteria (e.g., kappa statistics);; Quantitative PET uptake metrics (SUVmax, SUVmean) will be correlated with histologic markers of tumor grade, vascular invasion, and PSMA expression, when pathology samples are available.	1: Within 30 days of imaging; 2: Up to 90 days post-imaging (when surgical specimens are available)

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Collaborators: Miami VA Healthcare System
• Investigators: Principal Investigator: Binu V John, MD MPH, Miami VA Healthcare System, Miami, FL

Publications and helpful links

General Publications

• John BV, Aubuchon S, Dahman B, Konjeti VR, Heuman D, Hubert J, Thomas S, Deng Y, Solomon C, Sundaram LT, Love E, Singal AG, Tatum JL. Addition of [18 F]Fluorodeoxyglucose Positron Emission Tomography With Computed Tomography to Cross-Sectional Imaging Improves Staging and Alters Management in Hepatocellular Carcinoma. Liver Transpl. 2020 Jun;26(6):774-784. doi: 10.1002/lt.25743. Epub 2020 May 8.

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2024
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): September 30, 2028

Study Registration Dates

• First Submitted: June 5, 2025
• First Submitted That Met QC Criteria: June 5, 2025
• First Posted (Actual): June 13, 2025

Study Record Updates

• Last Update Posted (Actual): July 23, 2025
• Last Update Submitted That Met QC Criteria: July 17, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: ONCC-006-23S; 1761959 (Other Identifier: VA Central Institutional Review Board Panel); 1I01CX002654-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The United States Department of Veterans Affairs (VA) places legal restrictions on access to Veterans' healthcare data, including identifying and sensitive patient information. The analytic datasets used in this study were not permitted to leave the VA firewall without data-use agreement. This limitation is consistent with those of other studies based on VA data. However, VA data are freely available to researchers behind the VA firewall with an approved VA study protocol. For more information, please visit https://www.virec.research.va.gov or contact the VA Information Resource Center (VIReC) at Virec@Va.gov.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No