Impact of Surgical Resection on Hepatocellular Carcinoma Following Systemic Drug Therapy: A Multicenter Retrospective Observational Study

Aim This study is aimed to evaluate the safety and outcomes of surgical resection in patients with hepatocellular carcinoma (HCC) treated with systemic therapy, address the therapeutic benefit, and identify candidates for surgery after systemic treatment. Methods This retrospective cohort study was conducted at seven high‐volume centers in Japan, enrolling patients who underwent surgical resection for HCC after systemic drug therapy. Pre‐ and post‐treatment resectability criteria and oncological outcomes (progression‐free survival [PFS], overall survival [OS], pathological complete response [pCR], and postoperative complications) were analyzed. Results The cohort included 96 patients (mean age 68.3 years). The first‐line systemic therapies were sorafenib, lenvatinib, atezolizumab plus bevacizumab, and durvalumab plus tremelimumab ( n = 2/60/33/1, respectively). The pre‐treatment oncological resectability criteria were R/BR1/BR2 ( n = 8/42/46, respectively) and the pre‐surgery criteria were R/BR1/BR2 ( n = 13/41/42, respectively). Surgical procedures included 87 hepatectomies (42 major, 45 minor) and 9 non‐hepatectomy procedures. The median PFS was 0.9 years with 1‐, 2‐, and 5‐year PFS rates of 45.2%, 35.0%, and 25.6%, and the median OS was 4.0 years with 1‐, 2‐, and 5‐year OS rates of 86.1%, 64.5%, and 39.9%, respectively. R0/1 resection rate was 83.3%, and pCR rate was 18.8%. Postoperative complications (Clavien‐Dindo grade ≥ IIIa) occurred in 18.8%, with a 30‐day mortality rate of 0% and a 90‐day mortality rate of 4.2%. R0/1 resection was independently associated with better PFS and OS. Conclusions Surgical resection following systemic therapy demonstrated favorable safety and long‐term outcomes in advanced HCC. R0/1 resection is a key determinant of the prognosis.