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

arXiv: https://arxiv.org/abs/2610.17603 · HTML: https://mlsanity.com/paper/2610.17603/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 18 of its 42 references that are in the map.
- First posted on arXiv 13 Oct 2026.

## Builds on (most cited first, 18 of 18)

- [A Simple Framework for Contrastive Learning of Visual Representations](https://mlsanity.com/paper/2002.05709/) (2020)
- [SGDR: Stochastic Gradient Descent with Warm Restarts](https://mlsanity.com/paper/1608.03983/) (2016)
- [Supervised Contrastive Learning](https://mlsanity.com/paper/2004.11362/) (2020)
- [Attention-based Deep Multiple Instance Learning](https://mlsanity.com/paper/1802.04712/) (2018)
- [Data Efficient and Weakly Supervised Computational Pathology on Whole Slide Images](https://mlsanity.com/paper/2004.09666/) (2020)
- [TransMIL: Transformer based Correlated Multiple Instance Learning for Whole Slide Image Classification](https://mlsanity.com/paper/2106.00908/) (2021)
- [Dual-stream Multiple Instance Learning Network for Whole Slide Image Classification with Self-supervised Contrastive Learning](https://mlsanity.com/paper/2011.08939/) (2020)
- [Virchow2: Scaling Self-Supervised Mixed Magnification Models in Pathology](https://mlsanity.com/paper/2408.00738/) (2024)
- [Benchmarking Self-Supervised Learning on Diverse Pathology Datasets](https://mlsanity.com/paper/2212.04690/) (2022)
- [Phikon-v2, A large and public feature extractor for biomarker prediction](https://mlsanity.com/paper/2409.09173/) (2024)
- [Morphological Prototyping for Unsupervised Slide Representation Learning in Computational Pathology](https://mlsanity.com/paper/2405.11643/) (2024)
- [Feature Re-Embedding: Towards Foundation Model-Level Performance in Computational Pathology](https://mlsanity.com/paper/2402.17228/) (2024)
- [Towards Large-Scale Training of Pathology Foundation Models](https://mlsanity.com/paper/2404.15217/) (2024)
- [TICON: A Slide-Level Tile Contextualizer for Histopathology Representation Learning](https://mlsanity.com/paper/2512.21331/) (2025)
- [Predicting Neoadjuvant Chemotherapy Response in Triple-Negative Breast Cancer Using Pre-Treatment Histopathologic Images](https://mlsanity.com/paper/2505.14730/) (2025)
- [MorphGen: Morphology-Guided Representation Learning for Robust Single-Domain Generalization in Histopathological Cancer Classification](https://mlsanity.com/paper/2509.00311/) (2025)
- [Weakly Supervised Teacher-Student Framework with Progressive Pseudo-mask Refinement for Gland Segmentation](https://mlsanity.com/paper/2603.08605/) (2026)
- [MorphDistill: Distilling Unified Morphological Knowledge from Pathology Foundation Models for Colorectal Cancer Survival Prediction](https://mlsanity.com/paper/2604.06390/) (2026)

## Abstract (arXiv)

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 discrimination: adipose tissue achieves an area under the receiver operating characteristic curve (AUC) of 0.622, stroma achieves 0.604, and both perform comparably to tumor epithelium (0.601-0.605). On Alliance/CALGB 89803, the single model achieves an AUC of 0.642, while the post hoc ensemble reaches a pooled out-of-fold AUC of 0.70 and a risk-group hazard ratio of 3.79 (95% confidence interval: 2.55-5.63). On the external SurGen colon cancer cohort (n=218), the single model and ensemble achieve AUCs of 0.669 and 0.678, respectively. Conclusions: These findings support tissue morphology as structural supervision for outcome-aware representation learning in colorectal cancer prognosis.