This multicenter retrospective study evaluated the efficacy and safety of selective internal radiation therapy (SIRT) combined with lenvatinib and PD-(L)1 inhibitors (SIRT-L-P) versus transarterial chemoembolization (TACE) combined with lenvatinib and PD-(L)1 inhibitors (TACE-L-P) in patients with HCC beyond up-to-seven criteria or with portal vein tumor thrombus (PVTT). Tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were compared between the two groups.

Consecutive patients with HCC beyond up-to-seven criteria or with PVTT treated with SIRT-L-P or TACE-L-P from June 2022 to October 2024 were screened. Tumor response was evaluated according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) and Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Clinical outcomes, including tumor response, PFS, OS, and AEs were compared between the two groups.

Inclusion Criteria:

• histologically or clinically confirmed diagnosis of HCC at BCLC stage B or C (extrahepatic metastases were allowed)
• Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1
• Child-Pugh class A or B7
• unresectable HCC with intrahepatic tumor beyond up-to-seven criteria and/or with PVTT.

Exclusion Criteria:

• receipt of other loco-regional therapies, including hepatic arterial infusion chemotherapy, external radiation therapy, or radioactive seed implantation
• Prior systemic therapy
• History of other malignancies
• incomplete medical records

Patients with intermediate-advanced HCC beyond up-to-seven criteria and/or with PVTT.