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Background <p>The prognostic significance of adjuvant transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI) remains controversial. Furthermore, current literature often overlooks the treatment timing, and conventional survival analyses fail to address the immortal time bias introduced by delayed TACE initiation. This study aimed to evaluate the true clinical value of adjuvant TACE after adjusting for this bias.</p> Methods <p>This retrospective multicenter study included 512 HCC patients with MVI who underwent curative hepatectomy with or without adjuvant TACE between 2018 and 2024. Propensity score matching (PSM) was used to balance baseline characteristics. To rigorously adjust for immortal time bias, landmark analysis at 2-, 4-, 6-, and 12-month after surgery, along with time-dependent Cox regression (TDC) analysis, was performed.</p> Results <p>In the entire cohort, conventional Kaplan–Meier analysis showed better overall survival (OS) and recurrence-free survival (RFS) in the TACE group than in the NO-TACE group (all <i>p</i> &lt; 0.05). However, landmark analysis showed improved OS at the 4-, 6-, and 12-month landmarks (HR 0.68, 0.70, 0.69, respectively), whereas RFS differed significantly only at the 6-month landmark (<i>p</i> = 0.020). TDC analysis showed that adjuvant TACE was associated with improved OS (HR 0.63, 95% CI 0.47–0.85, <i>p</i> = 0.002) but not RFS. In the subgroup with tumor size ≥ 5 cm, landmark analysis showed significant advantages in both OS and RFS (all <i>p</i> &lt; 0.05), and TDC analysis further revealed that adjuvant TACE was linked to improved OS (HR 0.46, 95% CI 0.30–0.69, <i>p</i> &lt; 0.001) and RFS (HR 0.66, 95% CI 0.47–0.92, <i>p</i> = 0.014).</p> Conclusion <p>Adjuvant TACE was associated with improved OS in HCC patients with MVI, particularly in high-risk patients with tumor size ≥ 5 cm, who showed consistent improvements in both OS and RFS. The potential benefit of adjuvant TACE may extend beyond the conventional early postoperative period in MVI patients with tumor size ≥ 5 cm.</p> Graphical Abstract <p></p>

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Effect of adjuvant transarterial chemoembolization on survival in hepatocellular carcinoma with microvascular invasion: a landmark analysis

  • 期刊论文

  • 发表日期：

    2026年4月21日

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  • Tian-Chen Zhang,
  • Wei-Li Jia,
  • Yu Cao,
  • Chen Feng,
  • Zhen-Qi Li,
  • Shuai Xu,
  • Yi-Lin Hu,
  • Fan Zhang,
  • Xiong Chen,
  • Nian-Xin Xia,
  • Wen-Chao Zhao,
  • Ming-Gen Hu,
  • Shu-Qun Cheng,
  • Xiu-Ping Zhang,
  • Rong Liu

摘要

Background

The prognostic significance of adjuvant transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI) remains controversial. Furthermore, current literature often overlooks the treatment timing, and conventional survival analyses fail to address the immortal time bias introduced by delayed TACE initiation. This study aimed to evaluate the true clinical value of adjuvant TACE after adjusting for this bias.

Methods

This retrospective multicenter study included 512 HCC patients with MVI who underwent curative hepatectomy with or without adjuvant TACE between 2018 and 2024. Propensity score matching (PSM) was used to balance baseline characteristics. To rigorously adjust for immortal time bias, landmark analysis at 2-, 4-, 6-, and 12-month after surgery, along with time-dependent Cox regression (TDC) analysis, was performed.

Results

In the entire cohort, conventional Kaplan–Meier analysis showed better overall survival (OS) and recurrence-free survival (RFS) in the TACE group than in the NO-TACE group (all p < 0.05). However, landmark analysis showed improved OS at the 4-, 6-, and 12-month landmarks (HR 0.68, 0.70, 0.69, respectively), whereas RFS differed significantly only at the 6-month landmark (p = 0.020). TDC analysis showed that adjuvant TACE was associated with improved OS (HR 0.63, 95% CI 0.47–0.85, p = 0.002) but not RFS. In the subgroup with tumor size ≥ 5 cm, landmark analysis showed significant advantages in both OS and RFS (all p < 0.05), and TDC analysis further revealed that adjuvant TACE was linked to improved OS (HR 0.46, 95% CI 0.30–0.69, p < 0.001) and RFS (HR 0.66, 95% CI 0.47–0.92, p = 0.014).

Conclusion

Adjuvant TACE was associated with improved OS in HCC patients with MVI, particularly in high-risk patients with tumor size ≥ 5 cm, who showed consistent improvements in both OS and RFS. The potential benefit of adjuvant TACE may extend beyond the conventional early postoperative period in MVI patients with tumor size ≥ 5 cm.

Graphical Abstract