Deepath-MSI: a clinic-ready deep learning model for microsatellite instability detection in colorectal cancer using whole-slide imaging

Abstract

Microsatellite instability (MSI) is crucial for immunotherapy selection and Lynch syndrome diagnosis in colorectal cancer. Despite recent advances in deep learning algorithms using whole-slide images, achieving clinically acceptable specificity remains challenging. In this large-scale multicenter study, we developed Deepath-MSI, a feature-based multiple instances learning model specifically designed for sensitive and specific MSI prediction, using 5070 whole-slide images from seven diverse cohorts. Deepath-MSI achieved an AUROC of 0.98 in the test set. At a predetermined sensitivity threshold of 95%, the model demonstrated 92% specificity and 92% overall accuracy. In a real-world validation cohort, performance remained consistent with 95% sensitivity and 91% specificity. Deepath-MSI could transform clinical practice by serving as an effective pre-screening tool, substantially reducing the need for costly and labor-intensive molecular testing while maintaining high sensitivity for detecting MSI-positive cases. Implementation could streamline diagnostic workflows, reduce healthcare costs, and improve treatment decision timelines.