A systematic review and meta-analysis evaluated the role of combining MRI Prostate Imaging Reporting & Data System (PI-RADS) with clinical data in determining the need for prostate biopsy in men with suspected clinically significant prostate cancer (csPCa). The study included 72 studies with 36,366 patients. Key findings showed that PI-RADS 4 and 5 lesions, along with prostate-specific antigen density (PSAD), were independently associated with a higher risk of csPCa. Avoiding biopsy in patients with PI-RADS category 3 or less and PSAD less than 0.10 ng/mL² reduced unnecessary biopsies by 30% or 48% compared to biopsy in all suspected patients, while maintaining high sensitivity (97% or 95%). The study suggests that prostate biopsies may not be necessary for patients with equivocal or negative MRI results and low PSAD. The findings highlight the importance of integrating MRI and clinical parameters to optimize biopsy decisions, reduce unnecessary procedures, and minimize the risk of missing csPCa. The study also identified limitations, including the need for further validation and the challenge of selecting the optimal strategy in clinical practice.A systematic review and meta-analysis evaluated the role of combining MRI Prostate Imaging Reporting & Data System (PI-RADS) with clinical data in determining the need for prostate biopsy in men with suspected clinically significant prostate cancer (csPCa). The study included 72 studies with 36,366 patients. Key findings showed that PI-RADS 4 and 5 lesions, along with prostate-specific antigen density (PSAD), were independently associated with a higher risk of csPCa. Avoiding biopsy in patients with PI-RADS category 3 or less and PSAD less than 0.10 ng/mL² reduced unnecessary biopsies by 30% or 48% compared to biopsy in all suspected patients, while maintaining high sensitivity (97% or 95%). The study suggests that prostate biopsies may not be necessary for patients with equivocal or negative MRI results and low PSAD. The findings highlight the importance of integrating MRI and clinical parameters to optimize biopsy decisions, reduce unnecessary procedures, and minimize the risk of missing csPCa. The study also identified limitations, including the need for further validation and the challenge of selecting the optimal strategy in clinical practice.