Attention-Based Multimodal Survival Prediction with Cross-Modal Bilinear Fusion

We introduce ProtoPathway, an interpretable-by-design multimodal framework for cancer survival prediction that unifies whole slide imaging and transcriptomics through encoders producing biologically grounded representations on both sides of the fusion. On the histopathology side, $K$ learnable morphological prototypes, trained end-to-end with the survival objective, serve as the slide representation itself: patches flow into prototype tokens via soft assignment, compressing variable-length patch sets into fixed task-adaptive tokens. On the genomic side, a bipartite graph neural network encodes gene expression within the Reactome pathway hierarchy, producing pathway embeddings that reflect both constituent genes and their broader biological context through bidirectional message passing over a shared gene--pathway graph. Cross-modal attention then operates over a compact prototype $\times$ pathway matrix in which prototypes query pathways, modeling the biological direction in which molecular programs give rise to tissue morphology. Because both axes carry stable task-learned identity, the attention matrix is itself an interpretability output, yielding native inference-time attribution across the full biological hierarchy, from genes through pathways and prototypes to spatial tissue maps. We evaluate on five TCGA cancer cohorts, demonstrating competitive or superior survival prediction with substantially improved biological interpretability and reduced computational cost, with interpretability claims validated through fold-stratified rank-based population-level analysis. Our source code, model weights, and Reactome pathways, together with a unified codebase reimplementing all multimodal survival baselines under identical preprocessing and evaluation, are available at: https://github.com/AmayaGS/ProtoPathway.

Multimodal survival prediction, a crucial yet challenging task, demands the integration of multimodal medical data (\eg Whole Slide Images (WSIs) and Genomic Profiles) to achieve accurate prognostic modeling. Given the inherent heterogeneity across modalities, the feature decoupling-fusion paradigm has emerged as a dominant approach. However, these methods have the following shortcomings: (1) fail to reduce the redundant information of modality features before decoupling, which negatively affects the feature decoupling and fusion effect;(2) lack the ability to model the fine-grained relationships of the features and capture the local information interactions between intra- and inter-modality features. To address these issues, we propose a \underline{H}ierarchical \underline{D}ecoupling-Fusion \underline{M}ixture-\underline{o}f-\underline{E}xperts (HDMoE) framework with two levels of MoE and \underline{R}andom \underline{F}eature \underline{R}eorganization (RFR) modules.In the first-level MoE, shared experts and routed experts are employed to remove redundant information and extract fine-grained specific features within each modality, while the second-level MoE facilitates fine-grained inter-modality feature decoupling. Besides, we design two RFR modules following each level of MoE to finely fuse intra- and inter-modality features, which can help the model capture more fine-grained relationships between modalities. Extensive experimental results on our private Liver Cancer (LC) and three TCGA public datasets confirm the effectiveness of our proposed method. Codes are available at https://github.com/ZJUMAI/HDMoE.

Multimodal learning has significantly advanced survival prediction by integrating pathology images with genomic data. However, clinical information, despite its critical role in reflecting a patient' s overall health, remains underutilized due to its discrete, sparse, and low-dimensional nature. Furthermore, the inherent heterogeneity across these modalities pose significant challenges in modeling cross-modal interactions. In this paper, we propose CIGTSurv, a Clinical Information Guided Tri-modal framework for Survival prediction. Specifically, we first design a holistic text template and use pretrained foundation models to transform clinical tabular data into high-dimensional tokenized embeddings. Using clinical information as an anchor, we then introduce a dual-level interaction mechanism: 1) a local prototype association (LPA) module based on cross-attention to explicitly learn token-level correspondences between different modalities, and 2) a global feature alignment (GFA) loss based on Maximum Mean Discrepancy (MMD) to implicitly enhance cross-modal distribution consistency. Extensive experiments on five TCGA cancer cohorts demonstrate that CIGTSurv achieves state-of-the-art (SOTA) survival prediction performance. Our source code is publicly available at https://github.com/Daijing-ai/CIGT-Surv.git.