Prostate imaging reporting and data system version 2.1 as a predictor of clinically significant and aggressive prostate cancer: a radical prostatectomy-validated study.

Background: Prostate cancer incidence continues to rise globally, emphasizing the need for improved diagnostic and risk-stratification tools. This study aimed to evaluate the performance of Prostate Imaging Reporting and Data System (PI-RADS) version 2.1 in detecting clinically significant prostate cancer (csPCa), identifying high-risk patients, and predicting adverse pathological outcomes using radical prostatectomy (RP) pathology as the reference standard. Methods: This retrospective study included 190 men who underwent preoperative multiparametric prostate magnetic resonance imaging (mpMRI) followed by RP. PI-RADS scores were independently assigned by two fellowship-trained radiologists and correlated with RP pathology. Results: Higher PI-RADS scores were strongly associated with higher radical prostatectomy Gleason scores (rpGSs), with each one-category increase yielding 8-10-fold higher odds of elevated rpGS (P<0.001). Associations remained significant after adjustment for age, prostate-specific antigen (PSA), and biopsy Gleason scores (bxGSs) [adjusted odds ratio (OR) 5.54-8.19, P<0.001]. Increasing PI-RADS categories were also significantly linked to extraprostatic extension, seminal vesicle invasion, lymphovascular invasion, perineural invasion, and pathological T3 (pT3) disease (P<0.001-0.042). Each category increase corresponded to a threefold increase in odds of pT3 disease [OR 3.02, 95% confidence interval (CI): 1.26-8.28, P=0.02]. Among diagnostic thresholds, PI-RADS ≥3 had the highest sensitivity but lower specificity, whereas PI-RADS ≥4 provided the best balance (accuracy 0.78-0.81; specificity 0.53-0.58). PI-RADS 5 showed the strongest association with aggressive disease features, including grade group ≥3 and pT3 status (accuracy 0.67-0.74). Incorporating MRI improved risk-prediction performance, increasing the concordance index (C-index) from 0.864 (biopsy-only) to 0.883-0.894 and raising the area under the curve (AUC) for csPCa detection from 0.88 to 0.91-0.92. Interobserver agreement was near-perfect (weighted κ=0.96). Conclusions: PI-RADS v2.1 is a robust predictor of clinically significant and aggressive prostate cancer, demonstrating excellent reliability and incremental value beyond clinical parameters and biopsy. PI-RADS ≥4 represents an optimal threshold for csPCa detection, while PI-RADS 5 identifies patients at highest risk for adverse pathology. MRI-integrated assessment should inform risk stratification, active surveillance selection, and surgical planning.