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SAGE: Semantic Explainability of Attention-Based Survival Models in Computational Pathology

arXiv:2608.028037.9h-index: 18
Predicted impact top 54% in CV · last 90 daysOriginality Incremental advance
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SAGE provides a scalable, model-agnostic framework for pathologists to interpret ABMIL survival model behavior at the cohort level, potentially aiding biomarker identification, by addressing the limitation of local-only explanations from attention maps.

This paper introduces Semantic Attention Global Explanations (SAGE), a post-hoc framework for extracting global, language-grounded explanations from frozen attention-based multiple instance learning (ABMIL) models in computational pathology. SAGE quantifies how 25 histological concepts relate to survival prediction risk across patient cohorts, recovering established prognostic features and revealing cancer-specific biology, such as a favorable angiogenic signature in renal cell carcinoma.

Attention-based multiple instance learning (ABMIL) is the predominant approach for slide-level prediction in computational pathology, yet its attention maps provide only local explanations: they indicate where a model focuses but not which histological features drive its predictions or how the model behaves across a patient cohort. We present Semantic Attention Global Explanations (SAGE), a post-hoc framework that extracts global, language-grounded explanations from a frozen ABMIL model. Using a pathology vision-language model, SAGE scores image patches against a dictionary of 25 histological concepts, aggregates these scores according to the model's learned attention, and quantifies how each concept relates to prediction risk across a cohort. Applied to survival prediction using seven TCGA cancer cohorts and three foundation models, SAGE recovered established prognostic features, such as the adverse association of necrosis, while revealing cancer-specific biology, including a favorable angiogenic signature in renal cell carcinoma consistent with known molecular subtypes. Ablation studies demonstrated that these associations depend on the model's learned attention rather than concept prevalence alone, and that the concept dictionary captures much of the prognostic information encoded by the foundation model features. Through semantically-grounded explanations, SAGE provides a scalable, model-agnostic framework for understanding what ABMIL survival models learn, enabling pathologists to interpret model behavior at the cohort level and offering the potential for biomarker identification.

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