AFP response-based model as a prognostic monitor in unresectable hepatocellular carcinoma management.

Abstract

e16211 Background: Increasing evidence showed atezolizumab plus bevacizumab (A+B) with transarterial therapies (ABT therapy) was a highly effective regimen for unresectable hepatocellular carcinoma (uHCC). While, it is still unclear whether dynamic changes of alpha-fetoprotein (AFP) can early predict tumor response, residual tumor activity, and prognosis of HCC patients in the era of combined therapy. This study aimed to explore the AFP trajectory patterns and its impact on clinical outcomes following ABT therapy. Methods: This retrospective study enrolled uHCC patients with baseline AFP levels ＞25 ng/mL who achieved normalization following ABT treatment. Analyses included time to first AFP-complete response (AFP-CR, AFP normalization measured from treatment initiation) and AFP-progression-free survival (AFP-PFS, defined as the time from the first normalization of AFP to the first documented recurrence of AFP). Results: Among the 276 patients who received ABT as first-line therapy, 91 patients had elevated baseline AFP level that normalized after treatment. The median time to first AFP-CR was 2.4 months. At the time of first AFP-CR, tumor response assessed by mRECIST criteria showed CR in 13 patients (14.3%), partial response (PR) in 58 patients (63.7%), and stable disease (SD) in 20 patients (22.0%), whereas assessment by RECIST 1.1 criteria recorded PR in 37 patients (40.7%) and SD in 54 patients (59.3%). Ultimately, disease progression occurred in 27 (29.7%) patients. Among the 44 patients who achieved a mRECIST-based radiological CR (rCR), it occurred later than AFP-CR in 29 patients (65.9%), with a median lag time of 3.0 months (IQR: 2.0-5.1). Of the remaining 15 patients with mRECIST-rCR, it was concurrent with AFP-CR in 10 patients (22.7%) and occurred earlier in 5 patients (11.4%). The median AFP-PFS was 24.5 months, closely aligning with median mRECIST-PFS of 27.4 months. A total of 73 patients maintained sustained normal AFP level until the last follow-up. Conclusions: AFP trajectories provide valuable information complementary to radiological assessment in the combined modality era. Further prospective study is warranted to solidify the utility of AFP trajectory patterns in optimizing management for uHCC.