Morphology-aware deep learning predicts colorectal cancer survival from whole-slide images

Hikmat Khan, Metin N. Gurcan, Anil Parwani, Wendy L. Frankel, Wei Chen +1

Background: Five-year survival prediction from hematoxylin-and-eosin whole-slide images could support risk stratification, but the task is weakly supervised, and the tissue morphologies carrying prognostic information remain incompletely characterized. Methods: We conducted a retrospective secondary analysis using TCGA-COAD/READ (n=562) for morphology-specific analysis, Alliance/ CALGB 89803 (n=424) for model development, and SurGen (n=218) for external evaluation. We propose MorphContrast, a morphology-aware contrastive multiple-instance learning framework that uses tissue labels as structural supervision for five-year survival prediction. MorphContrast combines gated-attention pooling with three auxiliary objectives: patch-level morphology labels define within-patient contrasts, outcome concordance or discordance defines cross-patient contrasts within matched morphologies, and diversity regularization discourages representational collapse. Morphology-matched patches from patients with discordant outcomes serve as hard negatives, encouraging prognostic discrimination within comparable histologic contexts. Results: Morphology-specific models show weak but distributed prognostic…