Accurate prediction of Prostate Imaging Reporting and Data System (PI-RADS) scores from multiparametric MRI (mpMRI) remains challenging, more so than clinically significant prostate cancer (csPCa) detection. Given the importance of lesion location in PI-RADS scoring, we evaluated whether incorporating prostate zonal masks improves PI-RADS prediction and csPCa detection across multiple architectures (3D ResNet-18, ResNet-50, and ViT) using a large-scale internal dataset. Anatomical guidance generally improved performance across architectures, with the best results achieved by ResNet-18 with 2-zone guidance for PI-RADS prediction (QWK = 0.511) and ResNet-50 with 5-zone guidance for csPCa detection (AUC = 0.809). Fine-tuned results on external datasets further demonstrated the benefits of anatomical guidance. Furthermore, models with anatomical guidance improved the utility of model-predicted PI-RADS scores for PI-RADS-based csPCa detection (positive defined as PI-RADS>=3). Combining model-predicted and expert-assigned PI-RADS scores significantly increased the AUC from 0.711 to 0.756 (p < 0.05), suggesting that AI-derived PI-RADS scores may provide complementary information to expert assessment for csPCa detection. Overall, our findings highlight the value of incorporating prostate zonal anatomy into deep learning-based prostate MRI assessment.

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