Prostate cancer (PCa) is the most common malignancy in men worldwide. Multiparametric MRI (mpMRI) improves the detection of clinically significant PCa (csPCa); however, it remains limited by false-positive findings and inter-observer variability. Time-dependent diffusion (TDD) MRI provides microstructural information that may enhance csPCa characterization beyond standard mpMRI. This prospective observational diagnostic accuracy study protocol describes the evaluation of PROS-TD-AI, an in-house developed AI workflow integrating TDD-derived metrics for zone-aware csPCa risk prediction. PROS-TD-AI will be compared with PI-RADS v2.1 in routine clinical imaging using MRI-targeted prostate biopsy as the reference standard.

Prostate cancer (PCa) is the most frequently diagnosed malignancy in men and the eighth leading cause of cancer death worldwide. Multiparametric MRI (mpMRI) has become central to the diagnostic pathway for men at intermediate risk, improving detection of clinically significant PCa (csPCa) while reducing unnecessary biopsies and over-diagnosis. However, mpMRI remains limited by false positives, false negatives, and moderate to substantial interobserver agreement. Time-dependent diffusion (TDD) MRI, a novel sequence that enables tissue microstructure characterization, has shown encouraging preclinical performance in distinguishing clinically significant from insignificant PCa. Combining TDD-derived metrics with machine learning may provide robust, zone-specific risk prediction with less dependence on reader training and improved accuracy compared to current standard-of-care. This study protocol outlines the rationale and describes the prospective evaluation of a home-developed AI-enhanced TDD-MRI software (PROSTDAI) in routine diagnostic care, assessing its added value against PI-RADS v2.1 and validating results against MRI-guided prostate biopsy.