Abstract
The tumor microenvironment (TME) significantly influences the progression and prognosis of colorectal cancer (CRC). Key components, including the tumor-stroma ratio (TSR) and cancer-associated fibroblasts (CAFs), have been recognized as important prognostic markers in CRC. However, the conventional assessment of TSR and CAF density is often subjective and labor-intensive, limiting its clinical application. In this study, we employed an artificial intelligence (AI)-powered whole slide image (WSI) analyzer, Lunit SCOPE IO, to objectively quantify TSR and CAF density in stage II and III CRC specimens from 207 treatment-naïve patients. Our analysis revealed that both TSR (log-rank p<0.0001) and CAF (log-rank p=0.017) density were independently associated with disease-free survival (DFS), providing superior prognostic accuracy compared to conventional risk factors. Notably, incorporating TSR and CAF density with traditional high-risk criteria allowed for the reclassification of additional patients as high-risk, significantly improving DFS prediction and reducing false-negative rates. These findings highlight the potential of integrating AI-based histopathological analysis into routine clinical practice to enhance diagnostic precision, improve risk stratification, and ultimately optimize patient management in CRC.