From Representation Space to Prognostic Insights: Whole Slide Image Generation with Hierarchical Diffusion Model for Survival Prediction

Deep learning has significantly enhanced survival prediction using whole slide images (WSIs) by adopting a two-stage learning paradigm: WSI preparation and patient-level prediction. While existing research generally concentrates on developing advanced patient-level prediction modules, the critical importance of WSI preparation has been largely overlooked. In practice, WSI preparation is influenced by numerous factors, including tissue heterogeneity, sampling strategies, and technical considerations. These uncontrollable external factors incur variability in the number of WSIs among patients, introducing significant bias and resulting in inferior performance for patients with few WSIs. To address this challenge, we propose a novel approach named WSI-Diffusion. Unlike existing WSI generation models that produce augmented versions of input WSIs, our method generates entirely new WSIs in representation space to serve as complementary data. WSI-Diffusion employs a two-stage hierarchical diffusion process. Two novel modules, WSI-level and patch-level Diffusers are designed to capture complex correlations between WSIs and patches. The generated WSIs are integrated as supplementary data, and a light patient-level prediction module is then trained for survival prediction. Experimental results across five datasets demonstrate the superiority of our proposal.