A panel of kallikrein markers can reduce unnecessary biopsy for prostate cancer: data from the European Randomized Study of Prostate Cancer Screening in Göteborg, Sweden

Abstract

Background: Prostate-specific antigen (PSA) is widely used to detect prostate cancer. The low positive predictive value of elevated PSA results in large numbers of unnecessary prostate biopsies. We set out to determine whether a multivariable model including four kallikrein forms (total, free, and intact PSA, and human kallikrein 2 (hK2)) could predict prostate biopsy outcome in previously unscreened men with elevated total PSA.

Microfluidic integration for automated targeted proteomic assays

“…Recent ELISA-based formats offer notable gains in analytical sensitivity (10,11). Nevertheless, mounting evidence suggests that protein isoform "fingerprinting" could advance diagnostic performance (6,9,12). Unfortunately, ELISA is severely limited for isoform discrimination because antibodies specific to protein isoforms often do not exist (12).…”

Clinical Utility of Biomarkers in Localized Prostate Cancer

“…Moreover, in a meta-analysis incorporating 16 studies and 5856 patients, the pooled sensitivity and specificity were 0.85 (95 % CI, 0.83-0.86) and 0.45 (95 % CI, 0.44-0.47) for phi for overall PCa detection, respectively, and 0.90 (95 % CI 0.87-0.92) and 0.17 (95 % CI 0.14-0. 19) for Gleason ≥3+4 disease [17].…”

“…A panel of four serum kallikreins (total PSA, free PSA, intact PSA, and human kallikrein protein 2 (hK2) has received extensive evaluation in the pre-biopsy setting and is commercially marketed as the 4Kscore Test (4K, OPKO Lab, Nashville, TN) [19][20][21][22][23]24•]. The algorithm representing these components was initially derived from data based on participants within the European Randomized Study of Prostate Cancer Screening (ERSPC) and Prostate Testing for Cancer and Treatment (ProtecT) studies.…”

“…To date, the 4K test has been examined in over 15,000 patients within Europe and the USA. In one study, among 730 previously unscreened men within the Göteborg arm of the ERSPC, addition of the 4K to a base model improved the AUC for the prediction of PCa on biopsy from 0.87 to 0.90 [19]. Recently, Parekh et al reported on a prospective multi-centered US study of the 4K test in men scheduled to undergo prostate biopsy for clinical suspicion of PCa due to abnormal DRE or elevated PSA.…”

Risk-Based Prostate Cancer Screening: Who and How?

“…Vickers and colleagues used four serum kallikrein markers, including total PSA, free PSA, intact PSA, and kallikrein-related peptidase 2 to develop a statistical model to predict prostate biopsy results [81]. This model was successful in predicting the biopsy results in men with elevated PSA, suggesting that biopsy rates could be significantly reduced, while a relatively few men with elevated PSA levels and cancer would be advised not to undergo biopsy, most of whom would have low-grade disease [82].…”