A panel of kallikrein markers can predict outcome of prostate biopsy following clinical work-up: an independent validation study from the European Randomized Study of Prostate Cancer screening, France

Abstract

BackgroundWe have previously shown that a panel of kallikrein markers - total prostate-specific antigen (PSA), free PSA, intact PSA and human kallikrein-related peptidase 2 (hK2) - can predict the outcome of prostate biopsy in men with elevated PSA. Here we investigate the properties of our panel in men subject to clinical work-up before biopsy.MethodsWe applied a previously published predictive model based on the kallikrein panel to 262 men undergoing prostate biopsy following an elevated PSA (≥ 3 ng/ml) and further clinical work-up during the European Randomized Study of Prostate Cancer screening, France. The predictive accuracy of the model was compared to a "base" model of PSA, age and digital rectal exam (DRE).Results83 (32%) men had prostate cancer on biopsy of whom 45 (54%) had high grade disease (Gleason score 7 or higher). Our model had significantly higher accuracy than the base model in predicting cancer (area-under-the-curve [AUC] improved from 0.63 to 0.78) or high-grade cancer (AUC increased from 0.77 to 0.87). Using a decision rule to biopsy those with a 20% or higher risk of cancer from the model would reduce the number of biopsies by nearly half. For every 1000 men with elevated PSA and clinical indication for biopsy, the model would recommend against biopsy in 61 men with cancer, the majority (≈80%) of whom would have low stage and low grade disease at diagnosis.ConclusionsIn this independent validation study, the model was highly predictive of prostate cancer in men for whom the decision to biopsy is based on both elevated PSA and clinical work-up. Use of this model would reduce a large number of biopsies while missing few cancers.

Commercialized biomarkers: new horizons in prostate cancer diagnostics

“…The OPKO panel has been demonstrated in over 8,500 patients to predict the probability of cancer-positive biopsies in men suspected of having PCa. Retrospective studies have shown that the use of the panel could eliminate over 50% of unnecessary biopsies, with a probability of delaying diagnosis of a high grade cancer of only 0.6% (and this small population of men would be followed with active surveillance) [6,9].…”

“…This panel is based on markers used in a series of studies conducted in Europe and the U.S, assessing risk for clinically significant PCa [4][5][6][7][8][9][10]. The OPKO panel has been demonstrated in over 8,500 patients to predict the probability of cancer-positive biopsies in men suspected of having PCa.…”

Clinical Utility of Biomarkers in Localized Prostate Cancer

“…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.…”

Emerging biomarkers in the detection and prognosis of prostate cancer

“…In addition, the group led by Lilja and Vickers included hk2 in a multivariate model to predict the presence of PCa [61][62][63][64][65][66][67]. This model, which incorporates hk2, tPSA, fPSA, and iPSA, together with DRE, the age of the patient, and previous prostate biopsy, improves the accuracy obtained with other models.…”