Prostate cancer pathology plays a crucial role in clinical management but is time-consuming. Artificial intelligence (AI) shows promise in detecting prostate cancer and grading patterns. We tested an AI-based digital twin of a pathologist, vPatho, on 2,603 histology images of prostate tissue stained with hematoxylin and eosin. We analyzed various factors influencing tumor-grade disagreement between vPatho and six human pathologists. Our results demonstrated that vPatho achieved comparable performance in prostate cancer detection and tumor volume estimation, as reported in the literature. Concordance levels between vPatho and human pathologists were examined. Notably, moderate to substantial agreement was observed in identifying complementary histological features such as ductal, cribriform, nerve, blood vessels, and lymph cell infiltrations. However, concordance in tumor grading showed a decline when applied to prostatectomy specimens (kappa = 0.44) compared to biopsy cores (kappa = 0.70). Adjusting the decision threshold for the secondary Gleason pattern from 5% to 10% improved the concordance level between pathologists and vPatho for tumor grading on prostatectomy specimens (kappa from 0.44 to 0.64). Potential causes of grade discordance included the vertical extent of tumors toward the prostate boundary and the proportions of slides with prostate cancer. Gleason pattern 4 was particularly associated with discordance. Notably, grade discordance with vPatho was not specific to any of the six pathologists involved in routine clinical grading. In conclusion, our study highlights the potential utility of AI in developing a digital twin of a pathologist. This approach can help uncover limitations in AI adoption and the current grading system for prostate cancer pathology.
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