Assessing Foundation Models for Computational Pathology in Endometrial Cancer.

Computational pathology leverages deep learning to extract clinically relevant information from digitized tumor slides, predicting histopathological subtypes, molecular alterations, and patient outcomes. Recent pipelines increasingly rely on foundation models trained on large pan-cancer datasets to generate generalizable features. In endometrial cancer (EC), their comparative performance for clinical diagnostic tasks remains unexplored. This study evaluates the performance of seven state-of-the-art foundation models across morphological, molecular, and prognostic tasks using a large EC dataset of 3,293 patients from randomized trials and clinical cohorts. In addition, their performance was compared to two versions of an EC-specific feature extractor (EsVIT) exclusively trained on EC. The foundation models H-OPTIMUS-0, CONCH, and VIRCHOW2 achieved the highest mean performance, but the best-performing foundation model varied by task. The top-performing foundation model outperformed EsVIT across all tasks, which highlights the superiority of foundation models over the domain-specific feature extractor EsVIT in EC. Selecting the optimal foundation model for novel tasks remains challenging due to performance plateaus and limited information on the training datasets, requiring rigorous benchmarking and domain insight to reach maximum potential.