Transarterial Chemoembolization Following Curative Resection May Not Improve Survival for Hepatitis B Virus Associated Intrahepatic Cholangiocarcinoma: Propensity Score Weighting Analysis

Abstract

Background: For hepatocellular carcinoma (HCC), adjuvant transarterial chemoembolization (TACE) shows an advantageous response and prognosis in recurrent patients after resection. In consideration of similar pathogenesis and clinicopathological characteristics, studies should be conducted to ascertain whether hepatitis B virus (HBV)-associated intrahepatic cholangiocarcinoma (ICC) can be successfully treated by the methods used to treat HCC. The role of adjuvant TACE following liver resection for HBV-associated ICC remains controversial. This study aims to evaluate the efficacy of adjuvant TACE on recurrence and survival after liver resection, both before and after propensity score weighting (PSW) analysis.

Materials and methods: A total of 356 patients were categorized into two groups: i) 77 patients who received adjuvant TACE, and ii) 279 patients who underwent R0 resection alone. Staging was conducted according to the 8th edition of the American Joint Committee on Cancer (AJCC) Tumor-Node-Metastasis (TNM) staging system. Univariate and multivariate analyses were utilized to assess independent prognostic factors. Recurrence-free survival (RFS) and overall survival (OS) rates were compared using the Kaplan-Meier method.

Results: Among the 356 enrolled patients, 77 received adjuvant TACE. The median follow-up period was 45.3 months. Adjuvant TACE did not significantly affect OS (P=0.629) before or after PSW. Subgroup analyses indicated that TACE was not associated with OS across different TNM stages. After propensity score weighting, Cox regression model indicated significantly increased recurrence risk with TACE (HR=1.53, 95% CI: 1.02-2.28; P=0.0071). Stage-specific risks were visually summarized in Supplementary Figure 1. Additionally, TACE did not significantly impact RFS in TNM stage I (P=0.1720) and stage II (P=0.7905) subgroups. Conversely, TACE was positively associated with increased recurrence risk in TNM stage III (P=0.0014) and stage IV (P=0.0051) patients.

Conclusion: These findings suggest that adjuvant TACE following radical surgery does not prolong OS for patients with HBV-associated ICC. Furthermore, adjuvant TACE was associated with increased recurrence risk in TNM Stage III and IV subgroups, though this observation requires further validation due to sample size limitations in advanced stages.

Keywords: HBV; ICC; PSW; TACE; hepatitis B virus; intrahepatic cholangiocarcinoma; propensity score weighting; transarterial chemoembolization.

Figure 1

Kaplan-Meier survival analysis of OS and RFS before and after propensity score weighting. (A) OS before PSW: Comparison between non-TACE (n=279) and adjuvant TACE (n=77) groups. No significant difference was observed (Log-rank P=0.629). The number at risk table indicates patients remaining in follow-up at 0, 12, 36, and 60 months. Gray bands represent 95% confidence intervals. Median follow-up: 45.3 months (IQR: 29.7–59.2). (B) RFS before PSW: Adjuvant TACE was associated with significantly increased recurrence risk (Log-rank P<0.001). The 1-, 3-, and 5-year RFS rates were 42.9%, 34.6%, and 24.6% (TACE) vs 63.4%, 47.8%, and 45.7% (non-TACE). (C) OS after IPTW: Non-TACE (n=75) vs TACE (n=77) groups. After adjusting for baseline imbalances (all SMD<0.10), OS remained comparable (Log-rank P=0.425). (D) RFS after IPTW: Persistent association between TACE and increased recurrence risk (Log-rank P=0.007; Cox HR=1.53, 95% CI: 1.02–2.28).

Figure 2

Stage-stratified subgroup analysis of OS and RFS (E) OS in early-stage (I–II) ICC: Non-TACE (n=194) vs adjuvant TACE (n=55). No OS benefit with TACE (Log-rank P=0.138). (F) RFS in early-stage (I–II) ICC: No significant difference (Log-rank P=0.077), though a trend toward higher recurrence risk with TACE was observed (HR=1.27, 95% CI: 0.85–1.91). (G) OS in advanced-stage (III–IV) ICC: Non-TACE (n=85) vs TACE (n=22). TACE did not improve OS (Log-rank P=0.244). (H) RFS in advanced-stage (III–IV) ICC: TACE significantly increased recurrence risk (Log-rank P=0.001; HR=3.06, 95% CI: 1.78–5.26). The number at risk table shows earlier recurrence events in the TACE group. Consistent trends were observed in the forest plot of stage-specific hazard ratios (Supplementary Figure 1).