January 14, 2026Journal of Clinical Oncology0 citations

Pathological complete response after systemic conversion therapy and curative resection in initially unresectable hepatocellular carcinoma: Feasibility of a tumor-free for drug-free strategy.

TWTing WangWeifang Medical University YZYaojun ZhangJiangsu University ZWZhenling WangSichuan University

Key Points

This research investigates outcomes for patients with initially unresectable hepatocellular carcinoma achieving pCR after treatment and surgery.
Multicenter retrospective cohort study at three tertiary centers in China.
Included patients with initially unresectable hepatocellular carcinoma who received systemic therapy and curative resection.
Primary outcome was overall survival; secondary outcomes included recurrence-free survival and adverse events.
Out of 2212 patients, 257 achieved pathological complete response after treatment.
1-, 3-, and 5-year recurrence-free survival rates were 81.7%, 60.3%, and 58.3%; overall survival rates were 98.0%, 91.1%, and 85.5%.
Adjuvant therapy demonstrated comparable outcomes to active surveillance but higher adverse events.
Postoperative α-fetoprotein positivity correlated with worse recurrence-free and overall survival.

Abstract

496 Background: The outcomes and optimal postoperative management of patients with initially unresectable hepatocellular carcinoma (uHCC) who achieve pathological complete response (pCR) after systemic therapy and curative resection remains undefined. Methods: This multicenter retrospective cohort study included consecutive patients with initially uHCC who received systemic therapy followed by curative resection at three tertiary centers in China between January 2020 and December 2023. The primary outcome was overall survival (OS); secondary endpoints included recurrence-free survival (RFS) and incidence of treatment-related adverse events (AEs). Results: Among 2212 patients who underwent conversion surgery, 1623 (73.4%) received systemic therapy–based regimens; of these, 257 patients (15.8%) achieved pCR and were included in the analysis. The median tumor diameter was 9.0 cm, and 143 patients (55.6%) had macrovascular invasion. Most patients (87.2%) received immune checkpoint inhibitor (ICI)-based combination therapy. Postoperative adjuvant therapy was administered in 88 patients (34.2%) for a median duration of 6.05 months. After a median follow-up of 32.7 months, the 1-, 3-, and 5-year RFS rates were 81.7%, 60.3%, and 58.3%, and OS rates were 98.0%, 91.1%, and 85.5%, respectively. No significant differences in RFS or OS were observed between the adjuvant and surveillance groups, although AEs were more frequent in the adjuvant group. Postoperative α-fetoprotein (AFP) positivity was independently associated with worse RFS (HR, 3.3; P < .001) and OS (HR, 3.6; P = .0098). Conclusions: Patients with uHCC who achieve pCR after systemic conversion therapy and curative resection exhibit excellent long-term outcomes. Active surveillance yields comparable survival to adjuvant therapy with reduced toxicity. A “Tumor-Free for Drug-Free” strategy may be appropriate, particularly for patients with normalized postoperative AFP levels.

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