Persistent AFP Positivity After Liver-Directed Therapy Helps Predict Residual Disease Despite Imaging Response in Early-Stage Hepatocellular Carcinoma

Monday, March 31, 2025

3:45 PM – 3:54 PM CT

Location: Music City Center, 209 ABC

Presenting Author(s)

NU

Nathaniel Untch, MD

Medical Student
The University of Queensland Ochsner Clinical School, United States

Author/Co-author(s)

KN

Kelley Nunez, PhD

United States
TS

Tyler Sandow, MD

Interventional Radiologist
Ochsner Health, United States
Juan Gimenez, MD

Interventional Radiologist
Oschner Health, United States
AC

Ari Cohen, MD

Medical Director of Multi-Organ Transplant Institute
Multi-Organ Transplant Institute, Ochsner Health, New Orleans, LA, 70121, United States
PT

Paul Thevenot, PhD

Associate Professor
Ochsner Clinic Foundation, United States

Purpose: To evaluate the concordance between alpha-fetoprotein (AFP) and imaging responses per mRECIST in hepatocellular carcinoma (HCC) patients undergoing liver-directed therapy (LDT), and assess the impact of post-LDT AFP levels on retreatment decisions and outcomes.

Materials and Methods: This retrospective, single-center study analyzed data from 344 patients with unresectable HCC (all BCLC-A stage) receiving first-cycle LDT between (dates) as a bridge to transplantation or definitive treatment. Objective response (OR) was assessed per mRECIST; AFP positivity (AFP+) was defined as >8.4 ng/mL. Time-to-retreatment (TTR), time-to-progression (TTP), and progression-free survival (PFS) were evaluated.

Results: The cohort included 344 patients (72% male, 53% viral etiology). LDT modalities were 90Y (48%), MWA (25%), and TACE (27%). Pre-LDT, 54% were AFP+. Post-LDT, 41% remained AFP+, 13% converted to AFPNEG, 7% became AFP+, and 40% remained AFPNEG. LDT modality was associated with post-treatment AFP levels (P < 0.001); TACE had the highest percentage remaining AFP+ (54%) compared to MWA (31%) and 90Y (49%). OR was achieved in 85% per mRECIST. Post-LDT AFP+ was associated with a 5-fold increase in non-objective response (NOR) (25% vs 5%, P < 0.001). Among patients achieving OR, 42% remained AFP+ post-LDT. Those who remained AFP+ post-LDT had the highest 1-year progression risk (23%) compared to those who became AFP+ (14%), remained AFPNEG (3%), or converted to AFPNEG (0%).

Conclusion: Persistent AFP positivity after LDT indicates residual tumor. Patients remaining AFP+ post-LDT have a significantly higher risk of disease progression despite achieving OR per mRECIST. The discordance between AFP response and imaging suggests AFP is a valuable complementary biomarker for detecting residual disease in early-stage HCC. Incorporating AFP monitoring into post-treatment evaluations can aid in identifying patients who may benefit from aggressive retreatment when imaging alone is inconclusive. Integrating AFP response into clinical decision-making can enhance patient management and improve outcomes. Further prospective studies are recommended.