CIGTSurv: Clinical Information Guided Tri-modal Survival Prediction with Local Prototype Association and Global Feature Alignment

Multimodal survival analysis aims to improve cancer prognosis using heterogeneous biomedical data, such as histopathology images and genomic profiles. A common strategy is to align representations across modalities so that shared signals can be captured. However, strong cross-modal alignment can also remove modality-specific evidence that is critical for survival prediction. In this paper, we revisit multimodal survival learning from a simple observation: effective models should first discover shared patterns across modalities, and then preserve modality-specific signals. This motivates a representation learning principle that we refer to as Together Then Apart. Based on this idea, we propose TTA, a framework that balances cross-modal alignment and representation distinctiveness. TTA first performs prototype-based alignment to capture shared survival-related structures between modalities. It then encourages modality-specific distinctiveness through an anchor-guided contrastive objective. To further account for modality imbalance and noisy correspondences, we model cross-modal interactions using unbalanced optimal transport. We evaluate the proposed approach on multiple TCGA cancer cohorts with paired histopathology and genomic data. TTA consistently improves survival prediction over recent multimodal survival models. Moreover, the learned prototype structures reveal interpretable cross-modal patterns associated with clinical outcomes.

We propose a novel multimodal deep learning framework for patient-level survival prediction, which integrates whole-slide histology features, RNA-seq expression profiles, and clinical variables. Our architecture combines an ABMIL module~\cite{ilse2018attention} for slide-level representation with feedforward encoders for RNA and clinical data. These embeddings are then integrated through low-rank bilinear cross-modal fusion~\cite{liu2018efficient} to model conditional interactions across modalities while controlling parameter growth. The model outputs continuous risk scores that are subsequently mapped to survival times using a nonparametric calibration procedure based on the Kaplan--Meier estimator~\cite{kaplan1958nonparametric}. By decomposing multimodal reasoning into independent pairwise interactions, the proposed fusion design promotes structural interpretability and parameter efficiency compared with full tensor and hierarchical fusion strategies. Experiments on the CHIMERA challenge dataset demonstrate improved predictive performance over concatenation-based baselines and competitive generalization on hidden evaluation cohorts. These results indicate that the proposed framework is a promising approach for multimodal survival prediction in HR-NMIBC. The implementation is publicly available at https://github.com/hassancpu/ChimeraChallenge2025_Task_3.

Survival analysis plays a vital role in making clinical decisions. However, the models currently in use are often difficult to interpret, which reduces their usefulness in clinical settings. Prototype learning presents a potential solution, yet traditional methods focus on local similarities and static matching, neglecting the broader tumor context and lacking strong semantic alignment with genomic data. To overcome these issues, we introduce an innovative prototype-based multimodal framework, FeatProto, aimed at enhancing cancer survival prediction by addressing significant limitations in current prototype learning methodologies within pathology. Our framework establishes a unified feature prototype space that integrates both global and local features of whole slide images (WSI) with genomic profiles. This integration facilitates traceable and interpretable decision-making processes. Our approach includes three main innovations: (1) A robust phenotype representation that merges critical patches with global context, harmonized with genomic data to minimize local bias. (2) An Exponential Prototype Update Strategy (EMA ProtoUp) that sustains stable cross-modal associations and employs a wandering mechanism to adapt prototypes flexibly to tumor heterogeneity. (3) A hierarchical prototype matching scheme designed to capture global centrality, local typicality, and cohort-level trends, thereby refining prototype inference. Comprehensive evaluations on four publicly available cancer datasets indicate that our method surpasses current leading unimodal and multimodal survival prediction techniques in both accuracy and interpretability, providing a new perspective on prototype learning for critical medical applications. Our source code is available at https://github.com/JSLiam94/FeatProto.