Pre-treatment S-index as a promising prognostic indicator of treatment response and survival in patients with synchronous colorectal liver metastases: A retrospective multi-center study

Abstract

Background

Patients with synchronous colorectal cancer liver metastasis (CRLM) often face sub-optimal outcomes from systemic therapy or resection. This study investigates the prognostic value of the pre-treatment S-index, a reliable non-invasive marker for liver fibrosis, for outcomes in synchronous CRLM patients.

Methods

This study included two populations of patients with synchronous CRLM: one population undergoing resection and another population receiving systemic therapy for unresectable CRLM. Pre-treatment S-index levels were assessed from blood samples. Patients were categorized into high and low S-index groups, and comparisons were made regarding outcomes: progression-free survival (PFS), early post-operative recurrence and fibrosis in liver metastases in the resection population, and treatment response in the systemic therapy population. Multiplex immunohistochemistry/immunofluorescence (mIHC/IF) was used to investigate the distribution of immunosuppressive T-cell subsets in liver metastases.

Results

For synchronous CRLM patients receiving resection (n = 1000), patients with high preoperative S-index demonstrated significantly worse PFS both before (HR = 1.556, 95 % CI: 1.255–1.929; P < 0.001) and after IPTW-adjusted Cox proportional hazards regression analysis (IPTW-adjusted HR = 1.439, 95 % CI: 1.094–1.894; P = 0.036). High S-index patients also exhibited an elevated risk of early recurrence, both before and after adjustment (OR = 1.556, 95 % CI: 1.255–1.929, P < 0.001; IPTW-adjusted OR = 1.439, 95 % CI: 1.094–1.894, P = 0.009). For synchronous CRLM patients receiving system therapy (n = 123), a high pre-treatment S-index (OR = 34.691, P = 0.005) was a significant predictor of progression disease in multivariate analyses. Further, the S-index showed an AUC of 0.814 (95 %CI: 0.762–0.866, P < 0.001) for detecting fibrosis in liver metastases, with a specificity of 0.928. mIHC/IF analysis revealed that inhibitory T cells, especially CD4⁺PD1⁺ T cells and CD4⁺FOXP3⁺ T cells, were significantly elevated in the liver metastases of the high S-index group.

Conclusion

This study contributed valuable evidence regarding pre-treatment S-index for association with outcomes among synchronous CRLM patients receiving resection or system therapy. Furthermore, it underscores a significant association between a high S-index and the presence of fibrosis in liver metastases, as well as more infiltration of immunosuppressive T cells in the tumor.