GenoPath-MCA: Multimodal masked cross-attention between genomics and pathology for survival prediction

Survival prediction using whole slide images (WSIs) and bulk genes is a key task in computational pathology, essential for automated risk assessment and personalized treatment planning. While integrating WSIs with genomic features presents challenges due to inconsistent modality granularity, semantic disparity, and the lack of personalized fusion. We propose GenoPath-MCA, a novel multimodal framework that models dense cross-modal interactions between histopathology and gene expression data. A masked co-attention mechanism aligns features across modalities, and the Multimodal Masked Cross-Attention Module (M2CAM) jointly captures high-order image-gene and gene-gene relationships for enhanced semantic fusion. To address patient-level heterogeneity, we develop a Dynamic Modality Weight Adjustment Strategy (DMWAS) that adaptively modulates fusion weights based on the discriminative relevance of each modality. Additionally, an importance-guided patch selection strategy effectively filters redundant visual inputs, reducing computational cost while preserving critical context. Experiments on public multimodal cancer survival datasets demonstrate that GenoPath-MCA significantly outperforms existing methods in terms of concordance index and robustness. Visualizations of multimodal attention maps validate the biological interpretability and clinical potential of our approach.