Analyzing gigapixel Whole Slide Images (WSIs) is challenging due to the complex pathological tissue environment and the absence of target-driven domain knowledge. Previous methods incorporated pathological priors to mitigate this issue but relied on additional inference steps and specialized workflows, restricting scalability and the model’s capacity to identify novel outcome-related factors. To address these challenges, we propose a plug-and-play Pathology-Aware Mixture-of-Experts (PAMoE) module, which based on mixture of experts to learn pathology-related knowledge and extract useful information. We train the experts to become ‘specialists’ in specific intratumoral tissues by learning to route each tissue to its mapped expert. In addition, to reduce the impact of irrelevant content on the model, we introduce a new routing rule that discards patches in which none of the experts express interest, which helps the model better capture the relationships between relevant patches. Through a comprehensive evaluation of PAMoE on survival task, we demonstrate that 1) Our module enhances the performance of baseline models in most cases, and 2) The sparse expert processing across different tissues enhances the learning of patch representations by addressing tissue heterogeneity. Source code is available at https://github.com/wjx-error/PAMoE.

Survival prediction is a significant challenge in cancer management. Tumor micro-environment is a highly sophisticated ecosystem consisting of cancer cells, immune cells, endothelial cells, fibroblasts, nerves and extracellular matrix. The intratumor heterogeneity and the interaction across multiple tissue types profoundly impacts the prognosis. However, current methods often neglect the fact that the contribution to prognosis differs with tissue types. In this paper, we propose ProtoSurv, a novel heterogeneous graph model for WSI survival prediction. The learning process of ProtoSurv is not only driven by data but also incorporates pathological domain knowledge, including the awareness of tissue heterogeneity, the emphasis on prior knowledge of prognostic-related tissues, and the depiction of spatial interaction across multiple tissues. We validate ProtoSurv across five different cancer types from TCGA (i.e., BRCA, LGG, LUAD, COAD and PAAD), and demonstrate the superiority of our method over the state-of-the-art methods.