Perioperative tislelizumab for early-stage hepatocellular carcinoma: A phase II trial with integrated tumour microenvironment profiling and predictive modeling

Aims It is controversial whether monotherapy with immunotherapeutics is effective in early-stage hepatocellular carcinoma (HCC). We evaluated immunotherapy monotherapy as an initial neoadjuvant strategy. Methods This prospective, single-arm, phase II trial of an adaptive neoadjuvant strategy enrolled patients with resectable, early-stage HCC. All patients received tislelizumab monotherapy; non-responders received subsequent lenvatinib combination therapy preoperatively. Results For the overall efficacy of all 36 patients, the objective response rates were 13.9% and 30.6% as per the Response Evaluation Criteria in Solid Tumours v1.1 and modified Response Evaluation Criteria in Solid Tumours, respectively. Among the 33 patients who underwent resection, the major pathological response rate was 33.3% and the pathological complete response rate was 15.2%. Overall, grade ≥3 treatment-emergent adverse events occurred in 11.1%, with no surgical delays. Monotherapy responses were predicted by pretreatment tumour microenvironment features. Immune-regulatory cancer-associated fibroblasts colocalized with T cells identified responders, whereas angiogenic–metabolic signatures predicted resistance. A multimodal model integrating blood-based and imaging biomarkers accurately identified monotherapy-sensitive patients (average precision, 0.9167). The specificity for identifying responders was 100%. Conclusions These preliminary findings suggest that neoadjuvant immunotherapy monotherapy exhibits promising antitumour activity and demonstrates a manageable safety profile in early-stage HCC. The tailored stratification approach appears clinically feasible and may help minimize unnecessary exposure to combination therapy-related toxicity while retaining tentative therapeutic efficacy.