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.