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. 2025 Oct 1.
doi: 10.1038/s41551-025-01516-3. Online ahead of print.

Benchmarking foundation models as feature extractors for weakly supervised computational pathology

Affiliations

Benchmarking foundation models as feature extractors for weakly supervised computational pathology

Peter Neidlinger et al. Nat Biomed Eng. .

Abstract

Numerous pathology foundation models have been developed to extract clinically relevant information. There is currently limited literature independently evaluating these foundation models on external cohorts and clinically relevant tasks to uncover adjustments for future improvements. Here we benchmark 19 histopathology foundation models on 13 patient cohorts with 6,818 patients and 9,528 slides from lung, colorectal, gastric and breast cancers. The models were evaluated on weakly supervised tasks related to biomarkers, morphological properties and prognostic outcomes. We show that a vision-language foundation model, CONCH, yielded the highest overall performance when compared with vision-only foundation models, with Virchow2 as close second, although its superior performance was less pronounced in low-data scenarios and low-prevalence tasks. The experiments reveal that foundation models trained on distinct cohorts learn complementary features to predict the same label, and can be fused to outperform the current state of the art. An ensemble combining CONCH and Virchow2 predictions outperformed individual models in 55% of tasks, leveraging their complementary strengths in classification scenarios. Moreover, our findings suggest that data diversity outweighs data volume for foundation models.

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Conflict of interest statement

Competing interests: J.N.K. declares consulting services for AstraZeneca, Bioptimus, Owkin, DoMore Diagnostics, Panakeia, AstraZeneca, Mindpeak and MultiplexDx. Furthermore, he holds shares in StratifAI, Synagen and Spira Labs, has received an institutional research grant by GSK and has received honoraria by AstraZeneca, Bayer, Daiichi Sankyo, Eisai, Janssen, Merck, MSD, BMS, Roche, Pfizer and Fresenius. D.T. has received honoraria for lectures by Bayer and holds shares in StratifAI and Synagen. S.F. has received honoraria from MSD and BMS. R.L. declares consulting services and honoraria from MSD, Janssen, AstraZeneca, Astellas and Roche. A.M. has received honoraria as a consultant, advisor or speaker from Roche, Lilly and Menarini/Stemline, and has received support for accommodation and travel from AstraZeneca, all outside the submitted work. O.S.M.E.N. holds shares in StratifAI GmbH. The other authors declare no competing interests.

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