Jia-Min Wu, Guan-Hua Li, Cheng-Chun Lee, Jie-Ying Chen, Shun-Fa Yang, Kuan-Chun Hsueh
In patients receiving first-line MKIs, prior curative resection was associated with longer OS and PFS. The better liver reserve and more favorable tumor biology that made these patients suitable candidates for surgery may persist into the systemic therapy phase. Therefore, future clinical trials might consider prespecifying prior resection as a stratification factor.
BACKGROUND: Curative hepatectomy is the treatment of choice for resectable hepatocellular carcinoma (HCC). For recurrence or progression beyond locoregional therapy (LRT), multikinase inhibitors (MKIs) remain established first-line options. However, whether prior curative resection is associated with a survival benefit after MKI initiation remains unclear. We employed inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) to compare survival in MKI-treated patients with and without prior hepatectomy.
METHODS: This retrospective cohort study enrolled 203 patients with unresectable HCC receiving first-line sorafenib or lenvatinib at a single Taiwanese referral hospital (2018-2023). Patients were classified into recurrent HCC (rHCC, n = 58; with prior curative resection) and primary unresectable HCC (uHCC, n = 145; without prior resection) groups. Overall survival (OS) and progression-free survival (PFS) were evaluated using stabilized IPTW with multivariable Cox regression, and PSM as a sensitivity analysis.
RESULTS: Over a 13.2-month median follow-up, median OS was longer in the rHCC group (27.0 vs 11.8 months; P = 0.027). After IPTW adjustment, prior resection was independently associated with longer OS (HR: 0.54; 95% CI: 0.36-0.81; P = 0.003) and PFS (HR: 0.61; 95% CI: 0.42-0.89; P = 0.010). PSM yielded concordant results (OS HR: 0.42; 95% CI: 0.26-0.70; P < 0.001; PFS HR: 0.55; 95% CI: 0.35-0.86; P = 0.010). This survival advantage was primarily observed in patients with late recurrence (≥24 months from hepatectomy). High tumor burden was an independent adverse prognostic factor for OS (HR: 1.58; 95% CI: 1.08-2.30; P = 0.017).
CONCLUSION: In patients receiving first-line MKIs, prior curative resection was associated with longer OS and PFS. The better liver reserve and more favorable tumor biology that made these patients suitable candidates for surgery may persist into the systemic therapy phase. Therefore, future clinical trials might consider prespecifying prior resection as a stratification factor.