MorphDistill: Distilling Unified Morphological Knowledge from Pathology Foundation Models for Colorectal Cancer Survival Prediction

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.

Colorectal cancer (CRC) is the second most deadly and third most common cancer, and the leading cause of death among gastrointestinal cancers. Early diagnosis is crucial for the treatment of this cancer and increasing the survival rates. Although CRC is more common in developed regions, its occurrence is also increasing in developing regions as well. CRC diagnosis relies on histopathology assessment post-biopsy. Automated deep learning algorithms can significantly reduce diagnosis time, enhancing efficiency and supporting timely clinical decisions. We present an automated segmentation pipeline for whole-slide histopathology images that labels tumor grades 1-3 and normal mucosa. It utilizes dense prediction transformers with various encoder backbones, overlapping patches, and test-time augmentation. An adaptive augmentation policy, guided by large language models, further improves training. Top models were ensembled via soft voting, and mask refining post-processing steps, Gaussian blurring, morphological closing, and connected components analysis. On a colorectal cancer grade dataset, our method improved the F1 score from 62.92 to 69.84. Code is available here: github.com/caglarmert/ICIP2025

We present CRC-SAM, a unified framework for colorectal cancer segmentation across colonoscopy, CT, and histopathology images. Unlike prior single-modality methods, CRC-SAM provides consistent, modality-agnostic segmentation throughout the clinical workflow. Built on MedSAM, it incorporates low-rank adaptation (LoRA) layers into a frozen encoder, enabling efficient domain transfer to underrepresented modalities with minimal trainable parameters. Experiments on MSD-Colon, CVC-ClinicDB, and EBHI-Seg demonstrate superior performance across modalities, outperforming state-of-the-art baselines and highlighting the effectiveness of lightweight LoRA adaptation for foundation-model-based colorectal cancer analysis.