Non-invasive prostate cancer detection from MRI has the potential to revolutionize patient care by providing early detection of clinically-significant disease (ISUP grade group >= 2), but has thus far shown limited positive predictive value. To address this, we present an MRI-based deep learning method for predicting clinically significant prostate cancer applicable to a patient population with subsequent ground truth biopsy results ranging from benign pathology to ISUP grade group~5. Specifically, we demonstrate that mixed supervision via diverse histopathological ground truth improves classification performance despite the cost of reduced concordance with image-based segmentation. That is, where prior approaches have utilized pathology results as ground truth derived from targeted biopsies and whole-mount prostatectomy to strongly supervise the localization of clinically significant cancer, our approach also utilizes weak supervision signals extracted from nontargeted systematic biopsies with regional localization to improve overall performance. Our key innovation is performing regression by distribution rather than simply by value, enabling use of additional pathology findings traditionally ignored by deep learning strategies. We evaluated our model on a dataset of 973 (testing n=160) multi-parametric prostate MRI exams collected at UCSF from 2015-2018 followed by MRI/ultrasound fusion (targeted) biopsy and systematic (nontargeted) biopsy of the prostate gland, demonstrating that deep networks trained with mixed supervision of histopathology can significantly exceed the performance of the Prostate Imaging-Reporting and Data System (PI-RADS) clinical standard for prostate MRI interpretation.
Early prostate cancer detection and staging from MRI are extremely challenging tasks for both radiologists and deep learning algorithms, but the potential to learn from large and diverse datasets remains a promising avenue to increase their generalization capability both within- and across clinics. To enable this for prototype-stage algorithms, where the majority of existing research remains, in this paper we introduce a flexible federated learning framework for cross-site training, validation, and evaluation of deep prostate cancer detection algorithms. Our approach utilizes an abstracted representation of the model architecture and data, which allows unpolished prototype deep learning models to be trained without modification using the NVFlare federated learning framework. Our results show increases in prostate cancer detection and classification accuracy using a specialized neural network model and diverse prostate biopsy data collected at two University of California research hospitals, demonstrating the efficacy of our approach in adapting to different datasets and improving MR-biomarker discovery. We open-source our FLtools system, which can be easily adapted to other deep learning projects for medical imaging.