Objective <p>To develop and validate a biparametric magnetic resonance imaging(BpMRI) focused model for detecting clinically significant prostate cancer(csPCa)( Gleason score ≥ 7) in TZ PI-RADS 3 and 4 lesions, compared to the Risk-based model (PI-RADS ≥ 3 and PSA density (PSAD) ≥ 0.15 ng/ml/cm³).</p> Methods <p>A multi-center, retrospective cohort analysis was conducted on consecutive patients with PI-RADS 3 or 4 and eligible biopsy result. Multivariable logistic regression identified predictors of csPCa, followed by the areas under the curve(AUC) and decision curve analysis (DCA) comparisons between the Risk-based and BpMRI focused models, with external validation.</p> Results <p>A total of 121 patients with 231 lesions in the development cohort(cohort 1) and 45 patients with 81 lesions the external validation cohort(cohort 2) were included between January 2020 and December 2024. The AUCs of the BpMRI-focused model were higher than those of the risk-based model in both the development cohort (0.71 [95% CI: 0.62–0.81] vs. 0.83 [95% CI: 0.74–0.92], <i>p</i> &lt; 0.05) and the external validation cohort (0.75 [95% CI: 0.63–0.87] vs. 0.87 [95% CI: 0.79–0.95], <i>p</i> &lt; 0.05). Furthermore, the BpMRI Focused Model significantly reduced the number of false positives for clinically significant prostate cancer compared to the Risk-Based Model [54 (23%) vs. 142 (61%), <i>p</i> &lt; 0.002], while maintaining a cancer detection rate comparable to the PI-RADS ≥ 3 strategy (both <i>p</i> &gt; 0.05). Additionally, the BpMRI Focused Model achieved a higher biopsy avoidance rate for csPCa [15 (6%)] compared to the Risk-Based Model [10 (4%)], though the difference was not statistically significant (<i>p</i> = 0.30).</p> Conclusion <p>In clinical decision-making, lesions in the TZ with PI-RADS 3 or 4 can be incorporated into the BpMRI focused model to reduce unnecessary biopsies.</p> Graphical abstract <p></p>