Prognosis and Safety of Neoadjuvant Therapy Plus Surgery versus Upfront Surgery in Patients with Resectable Hepatocellular Carcinoma at CNLC Ib–IIa Stage: A Propensity Score Matching Study

Bohan Xiang,1– 3,* Lei Xu,1– 3,* Jieshen Shan,1– 3 Ruizhi Chang,1– 3 Qi Ge,1– 3 Chendong Wang,1– 3 Jia Song,1– 3 Xiaoping Chen,1– 3 Qiaodan Zhou,4 Lin Chen1– 31Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 2Hubei Provincial Clinical Medical Research Center for Liver Surgery, Wuhan, Hubei, 430030, People’s Republic of China; 3Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 4Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lin Chen, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, People’s Republic of China, Tel +86 13517260864, Email chenlin_tj@126.com Qiaodan Zhou, Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China, Tel +86 13407169244, Email qiaodanzhou@tjh.tjmu.edu.cnIntroduction: High-level evidence for neoadjuvant therapy in China Liver Cancer Staging (CNLC) Ib–IIa hepatocellular carcinoma (HCC) is lacking, and treatment duration is not standardized. This study aimed to compared prognosis and safety between neoadjuvant therapy plus surgery and upfront surgery, and to explore better neoadjuvant treatment duration, in CNLC Ib–IIa HCC patients.Method: This retrospective study included patients with CNLC stage Ib–IIa HCC who underwent liver resection at our center between 2019 and 2024. Patients were divided into neoadjuvant therapy group and upfront surgery group. Propensity score matching (PSM) was used to control for confounders. In the neoadjuvant therapy group, patients with stable disease (SD) or partial response (PR) after a short course of cycles were subdivided into a short-course group and an extended group. Endpoints were recurrence-free survival (RFS), overall survival (OS), and surgical safety.Results: Of 352 included patients (84 neoadjuvant, 268 upfront surgery), PSM yielded 79 pairs. The neoadjuvant therapy group had longer median RFS (not reached vs 26.5 months; HR 0.48, P < 0.001) and OS (HR 0.48, P < 0.05). Postoperative complications and textbook outcome did not differ. Among the neoadjuvant cohort, the extended group had superior median RFS compared with the short-course group (not reached vs 37.8 months, P = 0.007), with acceptable safety.Conclusions: Preoperative neoadjuvant therapy improves prognosis with acceptable safety in patients with resectable CNLC stage Ib–IIa HCC. In patients with SD/PR after a short course of neoadjuvant therapy, the extended strategy was associated with improved RFS compared with the short-course strategy.Keywords: hepatocellular carcinoma, liver resection, neoadjuvant therapy, neoadjuvant strategies