RATIONALE AND OBJECTIVES: Early prostate cancer detection and staging from MRI is extremely challenging for both radiologists and deep learning algorithms, but the potential to learn from large and diverse datasets remains a promising avenue to increase their performance within and across institutions. To enable this for prototype-stage algorithms, where the majority of existing research remains, we introduce a flexible federated learning framework for cross-site training, validation, and evaluation of custom deep learning prostate cancer detection algorithms. MATERIALS AND METHODS: We introduce an abstraction of prostate cancer groundtruth that represents diverse annotation and histopathology data. We maximize use of this groundtruth if and when they are available using UCNet, a custom 3D UNet that enables simultaneous supervision of pixel-wise, region-wise, and gland-wise classification. We leverage these modules to perform cross-site federated training using 1400+ heterogeneous multi-parameteric prostate MRI exams from two University hospitals. RESULTS: We observe a positive result, with significant improvements in cross-site generalization performance with negligible intra-site performance degradation for both lesion segmentation and per-lesion binary classification of clinically-significant prostate cancer. Cross-site lesion segmentation performance intersection-over-union (IoU) improved by 100%, while cross-site lesion classification performance overall accuracy improved by 9.5-14.8%, depending on the optimal checkpoint selected by each site. CONCLUSION: Federated learning can improve the generalization performance of prostate cancer detection models across institutions while protecting patient health information and institution-specific code and data. However, even more data and participating institutions are likely required to improve the absolute performance of prostate cancer classification models. To enable adoption of federated learning with limited re-engineering of federated components, we open-source our FLtools system at https://federated.ucsf.edu, including examples that can be easily adapted to other medical imaging deep learning projects.