To reduce unnecessary prostate biopsies (Pbx), better discrimination is needed. To identify clinically significant prostate cancer (
CSPC) we determined the performance of Lacdi NAc‐glycosylated prostate‐specific antigen ( LDN‐ PSA) and LDN‐ PSAnormalized by prostate volume ( LDN‐ PSAD). We retrospectively measured LDN‐ PSA, total PSA( tPSA), and free PSA/ tPSA(F/T PSA) values in 718 men who underwent a Pbx in 3 academic urology clinics in Japan and Canada (Pbx cohort) and in 174 PCpatients who subsequently underwent radical prostatectomy in Australia (preop‐ PSAcohort). The assays were evaluated using the area under the receiver operating characteristics curve ( AUC) and decision curve analyses to discriminate CSPC. In the Pbx cohort, LDN‐ PSAD( AUC0.860) provided significantly better clinical performance for discriminating CSPCcompared with LDN‐ PSA( AUC0.827, P= 0.0024), PSAD( AUC0.809, P< 0.0001), tPSA( AUC0.712, P< 0.0001), and F/T PSA( AUC0.661, P< 0.0001). The decision curve analysis showed that using a risk threshold of 20% and adding LDN‐ PSAand LDN‐ PSADto the base model (age, digital rectal examination status, tPSA, and F/T PSA) permitted avoidance of even more biopsies without missing CSPC(9.89% and 18.11%, respectively vs 2.23% [base model]). In the preop‐ PSAcohort, LDN‐ PSAvalues positively correlated with tumor volume and tPSAand were significantly higher in pT3, pathological Gleason score ≥ 7. Limitations include limited sample size, retrospective nature, and no family history information prior to biopsy. Lacdi NAc‐glycosylated PSAis significantly better than the conventional PSAtest in identifying patients with CSPC. This study was approved by the ethics committee of each institution (“The Study about Carbohydrate Structure Change in Urological Disease”; approval no. 2014‐195).