# The Prognostic Value of Tumor Fibrosis in Patients Undergoing Hepatic Metastasectomy for Colorectal Cancer: A Retrospective Pooled Analysis

## TL;DR

This study shows that anti-EGFR therapy leads to more tumor fibrosis than anti-VEGF in colorectal cancer liver metastases, suggesting it may be a better prognostic indicator.

## Contribution

The study compares anti-EGFR and anti-VEGF therapies in relation to tumor fibrosis and evaluates the Poultsides classification as a prognostic tool.

## Key findings

- Anti-EGFR therapy resulted in significantly higher fibrosis (median 40.0%) compared to anti-VEGF (median 20.6%).
- Overall survival was similar between the two treatment cohorts despite differences in fibrosis levels.
- The Poultsides classification may offer better prognostic value than the Rubbia–Brandt classification.

## Abstract

Surgical resection of liver metastases (M1) has shown a clear survival benefit in patients with metastatic colorectal cancer (mCRC). Several prognostic factors have been linked to differences in survival among these patients, including pathological tumor response. Tumor fibrosis in resected liver metastases has been associated with improved outcomes across different classifications, though no consistent cut-off for prognostic value has been established. This study aims to evaluate the likelihood of achieving ≥40% fibrosis following preoperative chemotherapy combined with either anti-epidermal growth factor receptor (anti-EGFR) or anti-vascular endothelial growth factor (anti-VEGF) therapy and its association with overall survival. Additionally, the study compares the prognostic value of two pathological response classifications: Poultsides vs. Rubbia–Brandt. Final outcomes aim to determine whether chemotherapy plus anti-EGFR leads to greater fibrosis and better prognosis than anti-VEGF. The study also seeks to validate the ≥40% fibrosis threshold as a more practical prognostic tool than the two-category Rubbia–Brandt classification.

Background: Colorectal cancer (CRC) is a significant global health burden, with liver metastases representing a key prognostic factor. Neoadjuvant chemotherapy (NAC) has improved outcomes in metastatic CRC (mCRC), and tumor regression is commonly assessed using the Rubbia–Brandt classification. The Poultsides classification defines ≥40% fibrosis as an independent prognostic factor, particularly in patients treated with cetuximab (45.71%). However, the predictive value of this threshold remains under debate, warranting further investigation. Methods: This study evaluates the extent of fibrosis (≥40%) induced by NAC plus anti-epidermal growth factor receptor (anti-EGFR) therapy vs. NAC plus anti-vascular endothelial growth factor (anti-VEGF) therapy in mCRC patients. It also examines the prognostic relevance of the Poultsides and Rubbia–Brandt classifications. A total of 108 patients undergoing liver resection for CRC metastases were included. Statistical analyses were performed using SPSS 28.0 version and R software 4.5 version to compare fibrosis rates and survival outcomes. Results: From September 2005 to January 2023, 108 patients were analyzed: 54 received chemotherapy plus anti-EGFR (Cohort 1), and 54 received chemotherapy plus anti-VEGF (Cohort 2). Fibrosis was significantly higher in Cohort 1 (median 40.0%, IQR: 25.4–53.2) than in Cohort 2 (median 20.6%, IQR: 8.07–36.9), p < 0.001. Overall survival was similar between both cohorts (p = 0.96), with a median follow-up of 41.6 months. Conclusions: Anti-EGFR therapy is associated with greater fibrosis than anti-VEGF, despite similar survival outcomes. The Poultsides classification may be a useful prognostic tool for resected liver metastases in mCRC.