Wendy L. Frankel

Hikmat Khan, Usama Sajjad, Metin N. Gurcan et al.

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. Accurate survival prediction is essential for treatment stratification, yet existing pathology foundation models often overlook organ-specific features critical for CRC prognostication. Methods: We propose MorphDistill, a two-stage framework that distills complementary knowledge from multiple pathology foundation models into a compact CRC-specific encoder. In Stage I, a student encoder is trained using dimension-agnostic multi-teacher relational distillation with supervised contrastive regularization on large-scale colorectal datasets. This preserves inter-sample relationships from ten foundation models without explicit feature alignment. In Stage II, the encoder extracts patch-level features from whole-slide images, which are aggregated via attention-based multiple instance learning to predict five-year survival. Results: On the Alliance/CALGB 89803 cohort (n=424, stage III CRC), MorphDistill achieves an AUC of 0.68 (SD 0.08), an approximately 8% relative improvement over the strongest baseline (AUC 0.63). It also attains a C-index of 0.661 and a hazard ratio of 2.52 (95% CI: 1.73-3.65), outperforming all baselines. On an external TCGA cohort (n=562), it achieves a C-index of 0.628, demonstrating strong generalization across datasets and robustness across clinical subgroups. Conclusion: MorphDistill enables task-specific representation learning by integrating knowledge from multiple foundation models into a unified encoder. This approach provides an efficient strategy for prognostic modeling in computational pathology, with potential for broader oncology applications. Further validation across additional cohorts and disease stages is warranted.

Usama Sajjad, Abdul Rehman Akbar, Ziyu Su et al.

Colorectal cancer (CRC) remains the third most prevalent malignancy globally, with approximately 154,000 new cases and 54,000 projected deaths anticipated for 2025. The recent advancement of foundation models in computational pathology has been largely propelled by task agnostic methodologies that can overlook organ-specific crucial morphological patterns that represent distinct biological processes that can fundamentally influence tumor behavior, therapeutic response, and patient outcomes. The aim of this study is to develop a novel, interpretable AI model, PRISM (Prognostic Representation of Integrated Spatial Morphology), that incorporates a continuous variability spectrum within each distinct morphology to characterize phenotypic diversity and reflecting the principle that malignant transformation occurs through incremental evolutionary processes rather than abrupt phenotypic shifts. PRISM is trained on 8.74 million histological images extracted from surgical resection specimens of 424 patients with stage III CRC. PRISM achieved superior prognostic performance for five-year OS (AUC = 0.70 +- 0.04; accuracy = 68.37% +- 4.75%; HR = 3.34, 95% CI = 2.28-4.90; p < 0.0001), outperforming existing CRC-specific methods by 15% and AI foundation models by ~23% accuracy. It showed sex-agnostic robustness (AUC delta = 0.02; accuracy delta = 0.15%) and stable performance across clinicopathological subgroups, with minimal accuracy fluctuation (delta = 1.44%) between 5FU/LV and CPT-11/5FU/LV regimens, replicating the Alliance cohort finding of no survival difference between treatments.