We present a multi-stage 3D computer-aided detection and diagnosis (CAD) model for automated localization of clinically significant prostate cancer (csPCa) in bi-parametric MR imaging (bpMRI). Deep attention mechanisms drive its detection network, targeting salient structures and highly discriminative feature dimensions across multiple resolutions. Its goal is to accurately identify csPCa lesions from indolent cancer and the wide range of benign pathology that can afflict the prostate gland. Simultaneously, a decoupled residual classifier is used to achieve consistent false positive reduction, without sacrificing high sensitivity or computational efficiency. In order to guide model generalization with domain-specific clinical knowledge, a probabilistic anatomical prior is used to encode the spatial prevalence and zonal distinction of csPCa. Using a large dataset of 1950 prostate bpMRI paired with radiologically-estimated annotations, we hypothesize that such CNN-based models can be trained to detect biopsy-confirmed malignancies in an independent cohort. For 486 institutional testing scans, the 3D CAD system achieves 83.69$\pm$5.22% and 93.19$\pm$2.96% detection sensitivity at 0.50 and 1.46 false positive(s) per patient, respectively, with 0.882$\pm$0.030 AUROC in patient-based diagnosis $-$significantly outperforming four state-of-the-art baseline architectures (U-SEResNet, UNet++, nnU-Net, Attention U-Net) from recent literature. For 296 external biopsy-confirmed testing scans, the ensembled CAD system shares moderate agreement with a consensus of expert radiologists (76.69%; $kappa$ $=$ 0.51$\pm$0.04) and independent pathologists (81.08%; $kappa$ $=$ 0.56$\pm$0.06); demonstrating strong generalization to histologically-confirmed csPCa diagnosis.