Defining Optimal Cut-offs for Absolute ADC and ADC Ratios in Clinically Significant Prostate Cancer: Correlation with PI-RADS v2.1 and Tumor Aggressiveness

Background To investigate the diagnostic value of apparent diffusion coefficient (ADC) values and ADC ratios (ADC _Ratio ) derived from multiparametric MRI (mpMRI) in differentiating benign from malignant peripheral zone lesions and identifying clinically significant prostate cancer (csPCa). Additionally, the study aims to evaluate the relationship between these quantitative parameters, PI-RADS v2.1 scores, and Gleason scores (GS). Methods A total of 188 patients who underwent pre-biopsy mpMRI between January 2021 and January 2025 were reviewed retrospectively. Based on histopathology, patients were stratified into Benign (n=126) and Malignant (n=62) groups. The Benign Group included lesion-free (Group 1, n=53) and lesion-positive (Group 2, n=73) cases. The Malignant Group was sub-classified into clinically non-significant (ncsPCa, Group 3, n=28) and significant cancer (csPCa, Group 4, n=34) according to ISUP standards. Age, PSA, prostate volume (PV), PSA density (PSAD), and PI-RADS scores were recorded. Lesion ADC values and ADC _Ratio (lesion-to-contralateral normal tissue) were calculated. Results In the study cohort (mean age: 63.36 ± 7.1 years), mean ADC values in the Malignant Group (767 ± 134 ×10 ^- ⁶ mm²/s) were significantly lower than in benign tissues (1606 ± 283 ×10 ^- ⁶ mm²/s; p<0.001). For benign-malignant differentiation, an ADC cut-off of 980 ×10 ^- ⁶ mm²/s yielded 98.4% sensitivity, 96.8% specificity, and an AUC of 0.99; an ADC _Ratio cut-off of 0.57 yielded an AUC of 0.98. In the csPCa group, mean ADC values (734 ×10 ^- ⁶ mm²/s) were significantly lower than in the ncsPCa group (807 ×10 ^- ⁶ mm²/s; p=0.032), with an optimal cut-off determined at 765 ×10 ^- ⁶ mm²/s. However, ADC _Ratio did not significantly differ between cancer subgroups (p=0.32). Higher PI-RADS scores were significantly correlated with increased PSAD, lower PV, and higher ISUP grades (p<0.05). Conclusions Lesion ADC values and ADC _Ratio demonstrate high diagnostic accuracy for prostate cancer detection. Specifically, absolute ADC values below 765 ×10 ^- ⁶ mm²/s serve as robust, independent predictors for csPCa. While ADC _Ratio excels in distinguishing benign from malignant lesions, its failure to stratify tumor aggressiveness supports the "field cancerization" hypothesis, suggesting microstructural changes in normal-appearing tissue in malignant conditions.