Vision Transformers with Autoencoders and Explainable AI for Cancer Patient Risk Stratification Using Whole Slide Imaging

Cancer remains one of the leading causes of mortality worldwide, necessitating accurate diagnosis and prognosis. Whole Slide Imaging (WSI) has become an integral part of clinical workflows with advancements in digital pathology. While various studies have utilized WSIs, their extracted features may not fully capture the most relevant pathological information, and their lack of interpretability limits clinical adoption. In this paper, we propose PATH-X, a framework that integrates Vision Transformers (ViT) and Autoencoders with SHAP (Shapley Additive Explanations) to enhance model explainability for patient stratification and risk prediction using WSIs from The Cancer Genome Atlas (TCGA). A representative image slice is selected from each WSI, and numerical feature embeddings are extracted using Google's pre-trained ViT. These features are then compressed via an autoencoder and used for unsupervised clustering and classification tasks. Kaplan-Meier survival analysis is applied to evaluate stratification into two and three risk groups. SHAP is used to identify key contributing features, which are mapped onto histopathological slices to provide spatial context. PATH-X demonstrates strong performance in breast and glioma cancers, where a sufficient number of WSIs enabled robust stratification. However, performance in lung cancer was limited due to data availability, emphasizing the need for larger datasets to enhance model reliability and clinical applicability.