Multi-Institutional Evaluation of Pathologists’ Assessment Compared to Immunoscore

SIMPLE SUMMARY: This study aims to compare the performance of the standardized consensus Immunoscore (IS) digital pathology assay to an evaluation of the immune response via visual examination of hematoxylin–eosin (H&E) slides and CD3+/CD8+ stained slides, achieved by expert pathologists. Herein, we report the evaluation of 540 stained images by multi-institutional pathologists to determine the concordance between pathologist assessment before and after training. The results show that the IS assay outperformed expert pathologists’ T-score evaluation in the clinical setting. This reveals the potential of the IS as an immune pathology tool, critical for reproducible quantitative analysis of tumor-infiltrated immune cells. These findings can contribute to a better diagnosis, allowing one to stratify cancer patients into reliable prognostic groups, based on the immune parameters quantified by IS. This work will likely impact the management of colon cancer patients as it raises the importance of the implementation of digital pathology in cancer diagnosis to provide appropriate personalized therapeutic decisions. ABSTRACT: Background: The Immunoscore (IS) is a quantitative digital pathology assay that evaluates the immune response in cancer patients. This study reports on the reproducibility of pathologists’ visual assessment of CD3+- and CD8+-stained colon tumors, compared to IS quantification. Methods: An international group of expert pathologists evaluated 540 images from 270 randomly selected colon cancer (CC) cases. Concordance between pathologists’ T-score, corresponding hematoxylin–eosin (H&E) slides, and the digital IS was evaluated for two- and three-category IS. Results: Non-concordant T-scores were reported in more than 92% of cases. Disagreement between semi-quantitative visual assessment of T-score and the reference IS was observed in 91% and 96% of cases before and after training, respectively. Statistical analyses showed that the concordance index between pathologists and the digital IS was weak in two- and three-category IS, respectively. After training, 42% of cases had a change in T-score, but no improvement was observed with a Kappa of 0.465 and 0.374. For the 20% of patients around the cut points, no concordance was observed between pathologists and digital pathology analysis in both two- and three-category IS, before or after training (all Kappa < 0.12). Conclusions: The standardized IS assay outperformed expert pathologists’ T-score evaluation in the clinical setting. This study demonstrates that digital pathology, in particular digital IS, represents a novel generation of immune pathology tools for reproducible and quantitative assessment of tumor-infiltrated immune cell subtypes.