A Four-kallikrein Panel Predicts High-grade Cancer on Biopsy: Independent Validation in a Community Cohort

BackgroundA statistical model based on four kallikrein markers (total prostate-specific antigen [tPSA], free PSA [fPSA], intact PSA, and human kallikrein-related peptidase 2) in blood can predict risk of Gleason score ≥7 (high-grade) cancer at prostate biopsy.ObjectiveTo determine the value of this model in predicting high-grade cancer at biopsy in a community-based setting in which referral criteria included percentage of fPSA to tPSA (%fPSA).Design, setting, and participantsWe evaluated the model, with or without adding blood levels of microseminoprotein-β (MSMB) in a cohort of 749 men referred for prostate biopsy due to elevated PSA (≥3 ng/ml), low %fPSA (<20%), or suspicious digital rectal examination at SkÃ¥ne University Hospital, Malmö, Sweden.Outcome measurements and statistical analysisThe kallikrein markers, with or without MSMB levels, measured in cryopreserved anticoagulated blood were combined with age in a published statistical model (Prostate Testing for Cancer and Treatment [ProtecT]) to predict high-grade cancer at biopsy. Predictive accuracy was compared with a base model.Results and limitationsThe %fPSA was low (median: 17; interquartile range: 13-22) in this cohort because this marker was used as a referral criterion. The ProtecT model improved discrimination over age and PSA for high-grade cancer (0.777 vs 0.720; p = 0.002). At one illustrative cut point, use of the panel would reduce the number of biopsies by 236 per 1000 and detect 195 of 208 (94%) but delay diagnosis of 13 of 208 high-grade cancers. MSMB levels in blood did not improve the accuracy of the panel (p = 0.2).ConclusionsThe kallikrein model is predictive of high-grade cancer if criteria for biopsy referral also include %fPSA, and it can reduce unnecessary biopsies without missing an undue number of tumors.Patient summaryWe evaluated a published model to predict biopsy outcome in men biopsied due to low percentage of free to total prostate-specific antigen. The model helps reduce unnecessary biopsies without missing an undue number of high-grade cancers.