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Purpose: To determine if pharmacokinetic modeling of DCE-MRI can diagnose CS-PCa in PI-RADS category 3 PZ lesions with subjective negative DCE-MRI. Materials and methods: In the present IRB approved, bi-institutional, retrospective, case–control study, we identified 73 men with 73 PZ PI-RADS version 2.1 category 3 lesions with MRI-directed-TRUS-guided targeted biopsy yielding: 12 PZ CS-PCa (ISUP Grade Group 2; N = 9, ISUP 3; N = 3), 27 ISUP 1 PCa and 34 benign lesions. An expert blinded radiologist segmented lesions on ADC and DCE images; segmentations were overlayed onto pharmacokinetic DCE-MRI maps. Mean values were compared between groups using univariate analysis. Diagnostic accuracy was assessed by ROC. Results: There were no differences in age, PSA, PSAD or clinical stage between groups (p = 0.265–0.645). Mean and 10th percentile ADC did not differ comparing CS-PCa to ISUP 1 PCa and benign lesions (p = 0.376 and 0.598) but was lower comparing ISUP ≥ 1 PCa to benign lesions (p < 0.001). Mean Ktrans (p = 0.003), Ve (p = 0.003) but not Kep (p = 0.387) were higher in CS-PCa compared to ISUP 1 PCa and benign lesions. There were no differences in DCE-MRI metrics comparing ISUP ≥ 1 PCa and benign lesions (p > 0.05). AUC for diagnosis of CS-PCa using Ktrans and Ve were: 0.69 (95% CI 0.52–0.87) and 0.69 (0.49–0.88). Conclusion: Pharmacokinetic modeling of DCE-MRI parameters in PI-RADS category 3 lesions with subjectively negative DCE-MRI show significant differences comparing CS-PCa to ISUP 1 PCa and benign lesions, in this study outperforming ADC. Studies are required to further evaluate these parameters to determine which patients should undergo targeted biopsy for PI-RADS 3 lesions. [ABSTRACT FROM AUTHOR]