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Background: Prostate cancer remains the second deadliest cancer for American men despite clinical advancements. Currently, magnetic resonance imaging (MRI) is considered the most sensitive non‐invasive imaging modality that enables visualization, detection, and localization of prostate cancer, and is increasingly used to guide targeted biopsies for prostate cancer diagnosis. However, its utility remains limited due to high rates of false positives and false negatives as well as low inter‐reader agreements. Purpose: Machine learning methods to detect and localize cancer on prostate MRI can help standardize radiologist interpretations. However, existing machine learning methods vary not only in model architecture, but also in the ground truth labeling strategies used for model training. We compare different labeling strategies and the effects they have on the performance of different machine learning models for prostate cancer detection on MRI. Methods: Four different deep learning models (SPCNet, U‐Net, branched U‐Net, and DeepLabv3+) were trained to detect prostate cancer on MRI using 75 patients with radical prostatectomy, and evaluated using 40 patients with radical prostatectomy and 275 patients with targeted biopsy. Each deep learning model was trained with four different label types: pathology‐confirmed radiologist labels, pathologist labels on whole‐mount histopathology images, and lesion‐level and pixel‐level digital pathologist labels (previously validated deep learning algorithm on histopathology images to predict pixel‐level Gleason patterns) on whole‐mount histopathology images. The pathologist and digital pathologist labels (collectively referred to as pathology labels) were mapped onto pre‐operative MRI using an automated MRI‐histopathology registration platform. Results: Radiologist labels missed cancers (ROC‐AUC: 0.75‐0.84), had lower lesion volumes (~68% of pathology lesions), and lower Dice overlaps (0.24‐0.28) when compared with pathology labels. Consequently, machine learning models trained with radiologist labels also showed inferior performance compared to models trained with pathology labels. Digital pathologist labels showed high concordance with pathologist labels of cancer (lesion ROC‐AUC: 0.97‐1, lesion Dice: 0.75‐0.93). Machine learning models trained with digital pathologist labels had the highest lesion detection rates in the radical prostatectomy cohort (aggressive lesion ROC‐AUC: 0.91‐0.94), and had generalizable and comparable performance to pathologist label‐trained‐models in the targeted biopsy cohort (aggressive lesion ROC‐AUC: 0.87‐0.88), irrespective of the deep learning architecture. Moreover, machine learning models trained with pixel‐level digital pathologist labels were able to selectively identify aggressive and indolent cancer components in mixed lesions on MRI, which is not possible with any human‐annotated label type. Conclusions: Machine learning models for prostate MRI interpretation that are trained with digital pathologist labels showed higher or comparable performance with pathologist label‐trained models in both radical prostatectomy and targeted biopsy cohort. Digital pathologist labels can reduce challenges associated with human annotations, including labor, time, inter‐ and intra‐reader variability, and can help bridge the gap between prostate radiology and pathology by enabling the training of reliable machine learning models to detect and localize prostate cancer on MRI. [ABSTRACT FROM AUTHOR]

Purpose: Magnetic resonance imaging (MRI) has great potential to improve prostate cancer diagnosis; however, subtle differences between cancer and confounding conditions render prostate MRI interpretation challenging. The tissue collected from patients who undergo radical prostatectomy provides a unique opportunity to correlate histopathology images of the prostate with preoperative MRI to accurately map the extent of cancer from histopathology images onto MRI. We seek to develop an open‐source, easy‐to‐use platform to align presurgical MRI and histopathology images of resected prostates in patients who underwent radical prostatectomy to create accurate cancer labels on MRI. Methods: Here, we introduce RAdiology Pathology Spatial Open‐Source multi‐Dimensional Integration (RAPSODI), the first open‐source framework for the registration of radiology and pathology images. RAPSODI relies on three steps. First, it creates a three‐dimensional (3D) reconstruction of the histopathology specimen as a digital representation of the tissue before gross sectioning. Second, RAPSODI registers corresponding histopathology and MRI slices. Third, the optimized transforms are applied to the cancer regions outlined on the histopathology images to project those labels onto the preoperative MRI. Results: We tested RAPSODI in a phantom study where we simulated various conditions, for example, tissue shrinkage during fixation. Our experiments showed that RAPSODI can reliably correct multiple artifacts. We also evaluated RAPSODI in 157 patients from three institutions that underwent radical prostatectomy and have very different pathology processing and scanning. RAPSODI was evaluated in 907 corresponding histpathology‐MRI slices and achieved a Dice coefficient of 0.97 ± 0.01 for the prostate, a Hausdorff distance of 1.99 ± 0.70 mm for the prostate boundary, a urethra deviation of 3.09 ± 1.45 mm, and a landmark deviation of 2.80 ± 0.59 mm between registered histopathology images and MRI. Conclusion: Our robust framework successfully mapped the extent of cancer from histopathology slices onto MRI providing labels from training machine learning methods to detect cancer on MRI. [ABSTRACT FROM AUTHOR]