To evaluate clinical efficacy and safety of sequential surgery after conversion therapy in patients with unresectable hepatocellular carcinoma (HCC).

Clinical data of 5 patients with initially unresectable HCC who underwent sequential surgical resection following conversion therapy in Affiliated Hospital of North Sichuan Medical College from February 2020 to July 2024 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. Among them, 4 patients were male and 1 female, aged from 33 to 73 years, with a median age of 53 years. All 5 cases were complicated with liver cirrhosis. 4 patients were assessed with Child-Pugh grade A and 1 case of Child-Pugh grade B liver function. The Eastern Cooperative Oncology Group Performance Status (ECOG-PS) scores were ranged from 0 to 1. According to the China Liver Cancer (CNLC) staging, 2 patients were classified with Ⅰb and 3 cases of Ⅲa stage tumor.The conversion therapeutic, operative regimen and effect, survival prognosis of the patients were summarized.

All 5 patients were treated with TACE-based local therapy combined with immunotherapy and targeted therapy. Among them, 1 case was treated with TACE+ bevacizumab + PD-1 inhibitor, 3 cases with TACE+TKIs+PD-1 inhibitor, and 1 case with TACE+TKIs+PD-1 inhibitor combined with HAIC. The duration of preoperative conversion therapy was 138 (109-311) d. All 5 patients had different degrees of adverse reactions, all of which were grade 2 or below. After symptomatic treatment, all the patients were alleviated without interruption of medication. The operation time was 330 (225-360) min, intraoperative blood loss was 250 (200-900) ml, and the length of hospital stay was 20 (15-27) d. Postoperative pathological results confirmed that resection margins were negative in all cases. Complete necrosis of tumor cells was found in 2 cases, who achieved pathological complete remission (pCR), and partial necrosis of tumor cells in 3 cases, who obtained pathological partial remission (pPR). For microvascular invasion (MVI) grade, 3 cases were with M0 and 2 with M1. Follow-up time was ranged from 3 to 44 months, with a median of 27 months. During the follow-up, 1 patient recurred at postoperative 21 months, and no recurrence or metastasis was observed after ablation treatment. No recurrence was observed in the remaining 4 cases. No death case was observed during the follow-up.

Surgical resection after TACE combined with immunotherapy and targeted therapy can prolong the survival time of patients with initially unresectable HCC. However, the specific regimen and efficacy remain to be validated by multiple prospective studies.