Predictors of False-Positive Results in Men with PI-RADS 4 Lesions

Background To identify predictive factors of false-positive results in men with PI-RADS 4 lesions on multiparametric MRI and to evaluate potential factors for improving risk stratification in this high-risk category. Methods We retrospectively analyzed 811 men with PI-RADS 4 lesions who underwent prostate biopsy (November 2020 - February 2025). Clinical data (age, PSA, PSA density (PSAD), prostate volume) and radiographic features (anatomical location (peripheral zone (PZ) vs. transitional zone (TZ)), multiplicity) were assessed. Multivariate logistic regression analysis identified independent predictors of false-positive results. Interaction between location and multiplicity was evaluated for zone-specific risk profiles. Results Of the 811 patients, 523 (64.5%) had benign pathology (false-positive). Independent predictors of false-positive results included younger age, lower PSAD, prior negative biopsy, and TZ location. TZ lesions had significantly higher odds of a false-positive result compared to PZ lesions (OR 6.919, 95% CI 4.440-10.781, p < 0.001). A divergent pattern was observed between location and multiplicity: in the PZ, multiplicity did not affect cancer risk, whereas in the TZ, multiple lesions showed a trend toward benign pathology ( p = 0.087), with the lowest predicted cancer probability (10.0%) in patients with multiple TZ lesions. Conclusion False-positive PI-RADS 4 assessments were associated with features characteristic of BPH, particularly TZ localization and lower PSAD. Current biopsy recommendations may be suboptimal for patients with these benign-favoring features. Incorporating lesion localization and volume-adjusted metrics into risk stratification could potentially reduce unnecessary biopsies.