To Biopsy or Not Biopsy, That is the Question - PI-Rads 3 Prostate Lesions – Validation of Clinical and Radiological Parameters for Biopsy Decision-Making

Objectives Multiparametric MRI (mpMRI) enhances prostate cancer (PCa) detection, especially when combined with targeted or MRI–ultrasound fusion biopsy. However, PI-RADS 3 lesions remain diagnostically indeterminate, with variable malignancy risk and heterogeneous clinical management. This study aims to identify predictive clinical and radiological factors for PCa and clinically significant PCa (csPCa) in patients with PI-RADS 3 lesions to improve risk stratification. Patients and Methods In this retrospective cohort study, 772 patients with 1,081 PI-RADS 3 lesions underwent mpMRI and MRI–ultrasound fusion-guided transrectal biopsy, including both targeted and systematic cores. Histopathological evaluation was based on ISUP grading. Logistic regression models were used to assess associations between clinical/radiological factors and biopsy outcomes. Results Overall cancer detection per lesion was 37.7%, with csPCa detected in 16.1% of lesions and 42.9% of positive biopsies. PSA density emerged as the strongest predictor of both PCa and csPCa, while prostate volume was inversely associated. csPCa was more commonly found in patients undergoing primary biopsy and those with posterior lesion localization. In selected low-risk groups, csPCa detection was rare, suggesting potential to avoid unnecessary biopsies, with specificity reaching up to 90%. Conclusions Overlapping benign conditions and interobserver variability contribute to uncertainty in the interpretation of PI-RADS 3 lesions with regard to the indication for biopsy. PSA density and clinical context support risk-adapted decision-making, aligning with current guideline recommendations. A personalized approach is recommended to balance the risks of under- and overdiagnosis in managing PI-RADS 3 lesions.