Liqin Yang, Ximing Wang, Zhiping Li, Fawei Huang, Yongsheng Zhang, Feng Ji Cui, Pengfei Jin
ABSTRACT Objective To explore the stratification differences of MRI and prostate‐specific antigen (PSA) density (PSAD) in the peripheral zone (PZ) and transition zone (TZ) lesions, in order to optimize the biopsy decision for patients with PSA 4–20 ng/mL. Methods This retrospective study analyzed 1524 patients undergoing MRI and biopsy. Lesions were grouped by PZ and TZ and the differences of PSAD within the subgroups were explored. A zonal‐specific risk matrix was constructed by integrating the Prostate Imaging Reporting and Data System (PI‐RADS) categories and PSAD in overall, PZ, and TZ cohorts. Low or high‐threshold pathway was constructed by 10% or 30% clinically significant prostate cancer (csPCa) probability for PZ and TZ. Six biopsy pathways were then formed and evaluated by the biopsy avoidance, csPCa detection, and positive predictive value (PPV). Finally, decision curve analysis (DCA) was employed to evaluate the net benefit associated with each pathway. Results PZ lesions exhibited higher PSAD than TZ counterparts in equivalent PI‐RADS categories ( p < 0.05). In the risk matrix, for PI‐RADS 1–2 lesions, TZ required PSAD ≥ 0.15 ng/mL/cm 3 while PZ ≥ 0.20 ng/mL/cm 3 to achieve > 10% csPCa risk. For PI‐RADS 3 lesions, thresholds were ≥ 0.15 ng/mL/cm 3 (TZ) and ≥ 0.20 ng/mL/cm 3 (PZ) to trigger biopsy at > 30% csPCa risk. Among six pathways, the “PZ high + TZ high” pathway (PSAD ≥ 0.20 ng/mL/cm 3 for PZ and ≥ 0.15 ng/mL/cm 3 for TZ in PI‐RADS 3) achieved optimal balance, detecting 86.6% of csPCa while avoiding 48.0% of unnecessary biopsies, with a PPV of 69.1% (F1‐score = 0.77). DCA confirmed superior net clinical benefit for this pathway at ≥ 20% risk thresholds. Conclusion In the risk stratification of MRI and PSAD, considering zonal specific of the lesion is helpful to improve biopsy decisions in patients with PSA 4–20 ng/mL.