Perioperative immunotherapy for resectable hepatocellular carcinoma - Authors'

# Perioperative immunotherapy for resectable hepatocellular carcinoma – Authors’ reply *The Lancet 2026* Correspondence 7 Chan SL, Zhou J, Wang L, et al. Article. The interim efficacy analysis and the Asian-Pacific Association for the Study of The Lancet Commission on addressing the was conducted in accordance with the Liver (APASL); has received travel support from global hepatocellular carcinoma burden: the Beijing Life Oasis Public Service Center, the comprehensive strategies from prevention to a protocol amendment approved Beijing Medical Award Foundation, the Chronic treatment. Lancet 2025; 406: 731–78. approximately 1 year before database Disease Prevention and Treatment of Traditional 8 Park JW, Chen M, Colombo M, et al. Global lock. The Lan–DeMets alpha spending Chinese Medicine Promotion Association, and the patterns of hepatocellular carcinoma Beijing Health Alliance Charitable Foundation; has management from diagnosis to death: the function was used to control served on data safety monitoring boards or advisory BRIDGE study. Liver Int 2015; 35: 2155–66. type 1 error. Although the originally boards for AstraZeneca and Merck Sharp & Dohme; planned sample size re-estimation and holds leadership or fiduciary roles in boards, Authors’ reply was retained, it ultimately became societies, committees, or advocacy organisations, including the Chinese Society of Oncology, the We read the Correspondence by unnecessary as the predefined Chinese Medical Association, APPLE, the Chinese Zhenli Lu and Yufu Tang in response efficacy boundary was crossed. All College of Surgeons, and APASL. All other authors to our Article,1 and welcome the procedures were prespecified to declare no competing interests. opportunity to respond. The maintain statistical rigour. Although Fei Liang, Shaolai Zhou, Zheng Wang, discrepancy in hepatocellular event-free survival includes subjective Jia Fan, *Jian Zhou, on behalf of the carcinoma resectability criteria reflects surgical judgement on resectability CARES-009 investigators inherent regional variations in health- (reflecting real-world clinical practice), zhou.jian@zs-hospital.sh.cn care infrastructure, epidemiological concordance between masked Department of Hepatobiliary Surgery and Liver profiles, and therapeutic frameworks. independent review committee and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China Recent updates to major international investigator assessments confirms (FL, SZ, ZW, JF, JZ) guidelines (eg, the Japan Society its robustness. Event-free survival 1 Wang Z, Fan J, Zhou S, et al. Perioperative of Hepatology’s 2021 version,2 the offers a more direct measure of initial camrelizumab plus rivoceranib versus surgery Korean Liver Cancer Association’s treatment efficacy than overall survival, alone in patients with resectable hepatocellular carcinoma at intermediate or 2022 version,3 and the American which is confounded by subsequent high risk of recurrence (CARES-009): a Association for the Study of Liver therapies.6–8 Overall survival follow- randomised phase 2/3 trial. Lancet 2025; Diseases’ 2023 version4) are actively up is ongoing (with final analysis 406: 4089–99. 2 Hasegawa K, Takemura N, Yamashita T, et al. re-evaluating surgery-centred scheduled at 70% of prespecified Clinical practice guidelines for hepatocellular multidisciplinary management for events), and exploratory sensitivity carcinoma: the Japan Society of Hepatology 2021 version (5th JSH-HCC Guidelines). advanced disease—an alignment that analyses (including rank-preserving Hepatol Res 2023; 53: 383–90. reinforces our study’s conceptual structural failure time models) are 3 Korean Liver Cancer Association and National framework. As mentioned, we planned to mitigate the effect of post- Cancer Center Korea. 2022 KLCA-NCC Korea practice guidelines for the management of urgently need the validation of recurrence crossover. We acknowledge hepatocellular carcinoma. Clin Mol Hepatol cross-sectional studies to promote that our trial was conducted exclusively 2022; 28: 583–705. the implementation of strategies in China, where approximately 80% 4 Singal AG, Llovet JM, Yarchoan M, et al. AASLD practice guidance on prevention, diagnosis, proposed in the future. With regard of cases of hepatocellular carcinoma and treatment of hepatocellular carcinoma. to the absence of an adjuvant- are related to hepatitis B virus Hepatology 2023; 78: 1922–65. 5 Zhou J, Sun H, Wang Z, et al. China Liver Cancer only control group (a limitation (ie, the leading cause of hepatocellular Guidelines for the diagnosis and treatment of acknowledged in our Article1), we carcinoma, responsible for 39% of hepatocellular carcinoma (2024 edition). plan to incorporate this comparator cases worldwide in 2022).8 Because Liver Cancer 2025; 14: 779–835. 6 Broglio KR, Berry DA. Detecting an overall in future trials to quantitatively assess this aetiological profile differs survival benefit that is derived from the independent contribution of from many non-endemic regions, progression-free survival. J Natl Cancer Inst 2009; 101: 1642–49. adjuvant treatment. We appreciate generalisability might be difficult. 7 Cabibbo G, Celsa C, Enea M, et al. Progression- Lu and Tang’s insightful feedback This limitation is acknowledged in free survival early assessment is a robust on our selection criteria, and on the Article. Confirmatory trials in surrogate endpoint of overall survival in immunotherapy trials of hepatocellular defining patients at intermediate to diverse geographical and aetiological carcinoma. Cancers (Basel) 2020; 13: 90. high recurrence risk. Our eligibility populations are needed. Finally, 8 Chan SL, Sun HC, Xu Y, et al. The Lancet criteria (ie, China Liver Cancer Staging although adjuvant transarterial Commission on addressing the global hepatocellular carcinoma burden: stage Ib–IIIa, endorsed by China’s chemoembolisation could complicate comprehensive strategies from prevention to National Health Commission5) were interpretation, its near-identical use treatment. Lancet 2025; 406: 731–78. validated across Barcelona Clinic Liver (ie, 86% in the perioperative group Cancer subgroups (figure 3 in the vs 87% in the surgery alone group) original Article1), supporting its broad makes confounding of the observed applicability. treatment effect unlikely. We also thank Wenyi Jin and JZ has received honoraria from the Asia–Pacific colleagues for their interest in our Primary Liver Cancer Expert Association (APPLE) 1334 --- [PDF原文](https://sci-net.xyz/storage/7932541/58dc8c9328f89422317b94354cf5170ce9991f18b2c273115d92d3e86a264c2d/Perioperative-immunotherapy-for-resectable-hepatocellular-carcinoma-Authors-reply.pdf) DOI: 10.1016/S0140-6736(26)00294-1