Hierarchical Multi-Scale Graph Learning with Knowledge-Guided Attention for Whole-Slide Image Survival Analysis

Cancer survival prediction from whole slide images (WSIs) is a challenging task in computational pathology due to the large size, irregular shape, and high granularity of the WSIs. These characteristics make it difficult to capture the full spectrum of patterns, from subtle cellular abnormalities to complex tissue interactions, which are crucial for accurate prognosis. To address this, we propose CrossFusion, a novel multi-scale feature integration framework that extracts and fuses information from patches across different magnification levels. By effectively modeling both scale-specific patterns and their interactions, CrossFusion generates a rich feature set that enhances survival prediction accuracy. We validate our approach across six cancer types from public datasets, demonstrating significant improvements over existing state-of-the-art methods. Moreover, when coupled with domain-specific feature extraction backbones, our method shows further gains in prognostic performance compared to general-purpose backbones. The source code is available at: https://github.com/RustinS/CrossFusion

Computational pathology involves the digitization of stained tissues into whole-slide images (WSIs) that contain billions of pixels arranged as contiguous patches. Statistical analysis of WSIs largely focuses on classification via multiple instance learning (MIL), in which slide-level labels are inferred from unlabeled patches. Most MIL methods treat patches as exchangeable, overlooking the rich spatial and topological structure that underlies tissue images. This work builds on recent graph-based methods that aim to incorporate spatial awareness into MIL. Our approach is new in two regards: (1) we deploy vision foundation-model embeddings to incorporate local spatial structure within each patch, and (2) achieve across-patch spatial awareness using graph neural networks together with a novel {\em jigsaw regularization}. We find that a combination of these two features markedly improves classification over state-of-the-art attention-based MIL approaches on benchmark datasets in breast, head-and-neck, and colon cancer.

The integrative analysis of histopathological Whole-Slide Images (WSIs) and transcriptomic profiles holds significant promise for cancer survival prediction. However, existing methods typically project multi-modal features directly into a shared latent space without explicit alignment, leading to the entanglement of mismatched morphological cues and molecular signals. Furthermore, current fusion strategies often treat the extreme spatial heterogeneity of WSIs uniformly, lacking mechanisms to adaptively prioritize clinically relevant tissue scales for individual patients. To address these limitations, we propose an Anchor-driven Multi-modal Multi-scale Expert Selection (AM$^2$ES) framework for survival prediction. Specifically, we present an Anchor-driven Multi-modal Fusion (AMF) module, which introduces learnable semantic anchors as cross-modal mediators to bridge the semantic gap by enforcing a structurally regularized alignment between transcriptomic features and multi-scale pathology representations. Built upon this aligned semantic space, we further design a Hierarchical Mixture-of-Experts (H-MoE) selection module to decouple the hierarchical prognostic selection process. Mimicking the pathologist's diagnostic workflow, H-MoE performs (i) Intra-scale Expert Filtering to discriminatively identify salient tumor regions within each magnification, and (ii) Inter-scale Hierarchy Routing to dynamically weight and select the most informative resolution levels. Extensive experiments on multiple TCGA cancer cohorts demonstrate that our AM$^2$ES achieves state-of-the-art performance while offering fine-grained interpretability by visualizing how specific molecular pathways drive the expert routing decisions across tissue scales. The code will be released at https://github.com/taozh2017/AM2ES.