Liver and Bile

Hepatology. 2025;81(6):1714-1727

Scheiner B, Kang B, Balcar L, Radu IP, Reiter FP, Adžić G, Guo J, Gao X, Yuan X, Cheng L, Gorgulho J, Schultheiss M, Peeters F, Hucke F, Ben Khaled N, Piseddu I, Philipp A, Sinner F, D’Alessio A, Pomej K, Saborowski A, Bathon M, Schwacha-Eipper B, Zarka V, Lampichler K, Nishida N, Lee PC, Krall A, Saeed A, Himmelsbach V, Tesini G, Huang YH, Vivaldi C, Masi G, Vogel A, Schulze K, Trauner M, Djanani A, Stauber R, Kudo M, Parikh ND, Dufour JF, Prejac J, Geier A, Bengsch B, von Felden J, Venerito M, Weinmann A, Peck-Radosavljevic M, Finkelmeier F, Dekervel J, Ji F, Wang HW, Rimassa L, Pinato DJ, Bouattour M, Chon HJ, Pinter M

Outcome and management of patients with hepatocellular carcinoma who achieved a complete response to immunotherapy-based systemic therapy

Background and aims: The outcome of patients with HCC who achieved complete response (CR) to immune-checkpoint inhibitor (ICI)-based systemic therapies is unclear.
Approach and results: Retrospective study of patients with HCC who had CR according to modified Response Evaluation Criteria in Solid Tumors (CR-mRECIST) to ICI-based systemic therapies from 28 centers in Asia, Europe, and the United States. Of 3,933 patients with HCC treated with ICI-based noncurative systemic therapies, 174 (4.4%) achieved CR-mRECIST, and 97 (2.5%) had CR according to RECISTv1.1 (CR-RECISTv1.1) as well. The mean age of the total cohort (male, 85%; Barcelona-Clinic Liver Cancer-C, 70%) was 65.9 ± 9.8 years. The majority (83%) received ICI-based combination therapies. Median follow-up was 32.2 (95% CI: 29.9–34.4) months. One- and 3-year overall survival rates were 98% and 86%. One- and 3-year recurrence-free survival rates were excellent in patients with CR-mRECIST-only and CR-RECISTv1.1 (78% and 55%; 70% and 42%). Among patients who discontinued ICIs for reasons other than recurrence, those who received immunotherapy for ≥ 6 months after the first mRECIST CR had a longer recurrence-free survival than those who discontinued immunotherapy earlier (p = 0.008). Of 9 patients who underwent curative surgical conversion therapy, 8 (89%) had pathological CR (CR-RECISTv1.1, n = 2/2; CR-mRECIST-only, n = 6/7).

Conclusions: Overall survival and recurrence-free survival of patients with CR-mRECIST-only and CR-RECISTv1.1 were excellent, and 6 of 7 patients with CR-mRECIST-only who underwent surgical conversion therapy had pathological CR. Despite potential limitations, these findings support the use of mRECIST in the context of immunotherapy for clinical decision-making. When considering ICI discontinuation, treatment for at least 6 months beyond CR seems advisable.

DOI:  10.1097/hep.0000000000001163