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

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Abstract
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 versus 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 and R software 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 better in Cohort 2 (p=0.003), 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.

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