Cross-attention fusion of biparametric MRI sequences with demographic and clinical variables for patient-level classification of clinically significant prostate cancer

Accurate patient-level risk stratification of clinically significant prostate cancer (csPCa) on biparametric MRI remains challenging, as most existing approaches require costly lesion-level annotations or have not been evaluated in large temporally separated cohorts. We developed and validated a multimodal deep learning framework combining T2-weighted (T2w), diffusion-weighted (DWI), and apparent diffusion coefficient (ADC) volumes with age, prostate-specific antigen (PSA), and PSA density (PSAD) for patient-level csPCa classification, trained without lesion-level annotations. The study included a retrospective development cohort of 3, 939 examinations and an independent temporal validation cohort comprising 1, 409 prospectively acquired examinations from 13 centers. The model employs three sequence-specific encoders with asymmetric cross-attention fusion and a two-stage transfer-learning strategy. Adding demographic and clinical variables consistently improved performance over MRI-only models, with PSAD emerging as the most informative complementary factor, primarily by improving specificity. The best-performing model—combining MRI, age, PSA, and PSAD with cross-attention—achieved a mean AUC of 0.765\!± \!0.006 on the retrospective held-out test set and 0.741\!± \!0.006 on the independent temporal validation cohort. Post hoc subgroup analyses suggested broadly stable rank-order discrimination (AUC) across most strata, though fixed-threshold sensitivity and specificity varied substantially, while Grad-CAM maps offered a qualitative indication of more frequent overlap with suspicious regions under cross-attention. These findings support PSAD-informed multimodal patient-level models as a viable tool for refined csPCa risk stratification on biparametric MRI, with potential to reduce false-positive classification of ISUP grade group 1 disease as clinically significant.