Background:The diagnostic value of current prostate-specific antigen (PSA) tests is challenged by the poor detection rate of prostate cancer (PCa) in repeat prostate biopsy.In this study,we proposed a novel PSA-related parameter named PSA density variation rate (PSADVR) and designed a clinical trial to evaluate its potential diagnostic value for detecting PCa on a second prostate biopsy.Methods:Data from 184 males who underwent second ultrasound-guided prostate biopsy 6 months after the first biopsy were included in the study.The subjects were divided into PCa and non-PCa groups according to the second biopsy pathological results.Prostate volume,PSA density (PSAD),free-total PSA ratio,and PSADVR were calculated according to corresponding formulas at the second biopsy.These parameters were compared using t-test or Mann-Whitney U-test between PCa and non-PCa groups,and receiver operating characteristic analysis were used to evaluate their predictability on PCa detection.Results:PCa was detected in 24 patients on the second biopsy.Mean values of PSA,PSAD,and PSADVR were greater in the PCa group than in the non-PCa group (8.39 μg/L vs.7.16 μg/L,0.20 vs.0.16,14.15％ vs.-1.36％,respectively).PSADVR had the largest area under the curve,with 0.667 sensitivity and 0.824 specificity when the cutoff was 10％.The PCa detection rate was significantly greater in subjects with PSADVR ＞10％ than PSADVR(≤)10％ (28.6％ vs.6.5％,P ＜ 0.001).In addition,PSADVR was the only parameter in this study that showed a significant correlation with mid-to-high-risk PCa ((r)=0.63,P =0.03).Conclusions:Our results demonstrated that PSADVR improved the PCa detection rate on second biopsies,especially for mid-to-high-risk cancers requiring prompt treatment.