DOI: 10.1177/27683605261477729 ISSN: 2768-3605

Sanshimao Formula Improves Recurrence-Free Survival in Early and Intermediate Hepatocellular Carcinoma Patients with Cirrhosis: A Randomized Controlled Trial

Wei Xie, Xiangyu Zhang, Jiawei Zhao, Yongbin Meng, Xia Li, Juan Du
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Background:

This study was designed to assess the safety and preliminary efficacy of Sanshimao (SSM) formula in early and intermediate hepatocellular carcinoma (HCC) patients with cirrhosis.

Methods:

We conducted a prospective randomized, open-label, controlled trial, assigning early and intermediate HCC patients with cirrhosis in a 1:1 ratio to either the control group or the SSM group. Patients were followed for a 16-month treatment period. Patients in the SSM group received additional SSM formula in addition to their conventional management compared with control. Primary analysis was performed in the intention-to-treat (ITT) population, and a sensitivity analysis was conducted in the per-protocol (PP) population. The primary endpoint was recurrence-free survival (RFS). Liver stiffness measurement (LSM), laminin-5 (LN-5), collagen type IV (COL IV), hyaluronic acid (HA), and procollagen type III (HPC III) were exploratory secondary endpoints.

Results:

A total of 106 patients were randomized (53 per group), and 90 patients who completed the study were included in the PP analysis. In the ITT population, the SSM group showed significantly improved RFS compared with control (hazard ratio [HR] = 0.47, 95% confidence interval [CI]: 0.27–0.81, p = 0.007). The PP sensitivity analysis yielded consistent findings (HR = 0.28, 95% CI: 0.15–0.52, p < 0.001). At the end of the 16-month treatment period, LSM levels in the SSM group were significantly lower than those in the control group (mean difference: –3.17 kPa, 95% CI: –5.45 to −0.89, p = 0.0018). Serum LN-5, COL IV, HA, and HPC III decreased significantly in the SSM group (all p < 0.05), whereas no significant changes were observed in the control group. No deaths or serious adverse events were reported in either group, and all reported adverse events were Grade 1 in severity.

Conclusion:

Adjuvant SSM formula significantly improved the RFS in early and intermediate HCC patients with cirrhosis after curative hepatectomy or locoregional therapy. Alongside the observed RFS benefits, reductions in liver stiffness and extracellular matrix biomarkers were also noted. However, a causal relationship between these outcomes remains unconfirmed.

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