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

BACKGROUND

A 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.

OBJECTIVE

To 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 PARTICIPANTS: We 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 Skåne University Hospital, Malmö, Sweden.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS

The 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 LIMITATIONS

The %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).

CONCLUSIONS

The 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 SUMMARY

We 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.