Diagnostic Performance of the Novel Biomarker S2,3PSA Density for Prostate Biopsy Optimization in Prostate Imaging Reporting and Data System 3–5 Lesions

Background This study evaluated the diagnostic accuracy of the novel biomarkers α2,3‐sialylated prostate‐specific antigen percentage (S2,3PSA%) and S2,3PSA density (S2,3PSAD) in patients classified into Prostate Imaging Reporting and Data System (PI‐RADS) categories 3–5 and examined their utility in optimizing prostate cancer (PCa) diagnosis. S2,3PSA% reflects cancer‐specific N‐glycan modifications of free PSA, and its volume‐adjusted index S2,3PSAD may improve diagnostic precision. Methods We enrolled patients who underwent prostate biopsy at our institution between October 2023 and May 2025, all with measurable S2,3PSA%, S2,3PSAD, and PI‐RADS 3–5 lesions on magnetic resonance imaging (MRI) scans. S2,3PSA% was measured using the μTASWako i50 system, and S2,3PSAD was calculated by dividing S2,3PSA% by prostate volume. The diagnostic performance (area under the curve [AUC], sensitivity, and specificity) of S2,3PSA% and S2,3PSAD was compared with that of conventional markers (prostate‐specific antigen [PSA] and prostate‐specific antigen density [PSAD]). Avoided biopsies and missed clinically significant PCa (csPCa, ISUP Grade Group ≥ 2) were also evaluated. Results Among 150 patients (median PSA, 7.18 ng/mL; prostate volume, 33.0 mL; PSAD, 0.20; S2,3PSA%, 43.2%; S2,3PSAD, 1.21), PCa and csPCa were detected in 95 (63%) and 84 (56%) patients, respectively. PSA and PSAD showed AUCs of 0.607/0.736 and specificities of 23.6%/40.0%, at 85.3% sensitivity. By contrast, S2,3PSA% and S2,3PSAD achieved higher AUCs of 0.737/0.757 and specificities of 45.5%/49.1%. In MRI‐targeted biopsy (MRI‐TBx) cases ( n = 85), PSA and PSAD had AUCs of 0.615/0.758 and specificities of 18.8%/43.8% at 88.7% sensitivity, whereas S2,3PSA% and S2,3PSAD reached 0.799/0.810 with specificities of 53.1%/56.3%. In PI‐RADS 3/4, S2,3PSAD exhibited the highest AUC (0.773). At < 0.85, avoided biopsy and csPCa miss rates were 26.4%/8.8% (MRI‐TBx: 29.2%/7.5%). No csPCa was missed in PI‐RADS 4 MRI‐TBx group, while PI‐RADS 5 showed higher miss rates. Conclusion S2,3PSA% and S2,3PSAD offer superior diagnostic accuracy compared to conventional markers, especially in MRI‐TBx and PI‐RADS 3/4, reducing unnecessary biopsies and minimizing missed csPCa. A biopsy remains warranted for PI‐RADS 5.