The Science Behind The 4Kscore® Test
The 4Kscore® Test is a follow-up blood test after an abnormal PSA (Prostate Specific Antigen) or digital rectal exam (DRE) to provide the probability of finding aggressive prostate cancer if a biopsy were to be performed. The 4Kscore® Test combines measurements of four prostate-specific biomarkers along with patient clinical information in an algorithm to accurately predict a man’s pobability for aggressive prostate cancer. Understanding the probability of finding aggressive prostate cancer gives a patient and a physician more information to decide if a prostate biopsy is warranted.
The 4Kscore® Test measures four prostate-specific kallikreins: Total PSA, Free PSA, Intact PSA, and human kallikrein 2 (hk2) in addition to incorporating clinical results. Total PSA and Free PSA are important markers for prostate cancer but have low specificity for risk of aggressive prostate cancer. Intact PSA and human kallikrein 2 (hk2) are present in much lower concentrations than total PSA and Free PSA, and changes in these biomarkers are associated with aggressive types of prostate cancer.
A prospective U.S.–based validation study of The 4Kscore® Test in 1012 men examined the accuracy of the test to predict the probability of high-grade cancer on biopsy and the contributions of the different test components. The Area Under the Curve (AUC) for The 4Kscore® Test was 0.82 compared to 0.74 for a PSA–based probablity calculator. Intact PSA and human kallikrein 2 (hk2) contributed 0.07 to the AUC of The 4Kscore Test, which was a significant contribution. The 4Kscore® Test predicted probability of high-grade cancer with high calibration to the true probability observed in the study.
Parekh DJ et al. Eur Urol. 2015 Sep;68(3):464-70
AUC = 0.82
36% of biopsies could be avoided or delayed
Study Results Show The 4Kscore® Test Performance at 5.0 Cut Point in the African American Population Identifies Men with High-Grade Prostate Cancer with 99% Sensitivity and 95% Negative Predictive Value (The 4Kscore® Test PI)
Punnen S et al. J Urol. 2018 Jun;199(6):1459-1463:
22% of study subjects could avoid or delay biopsies
Improving the Specificity of Screening for Lethal Prostate Cancer Using Prostate-specific Antigen and a Panel of Kallikrein Markers: A Nested Case–Control Study
Stattin et al. Eur Urol. 2015;68(2):207-213:
In 50- and 60-year-old men with an elevated PSA, a low-risk 4Kscore® was shown to predict low probability for metastasis.
"Twenty-year Risk of Prostate Cancer Death by Midlife Prostate-specific Antigen and a Panel of Four Kallikrein Markers in a Large Population-based Cohort of Healthy Men"
Sjoberg et al. Eur Urol. 2018;73(6):941-948:
The 4Kscore® Test can stratify men and predict distant prostate cancer mortality.
Parekh et al. A multi-institutional prospective trial in the USA confirms that the 4Kscore® accurately identifies men with high-grade prostate cancer. Eur Urol. 2015;68(3):464-470.
Punnen et al. A multi-institutional prospective trial confirms noninvasive blood test maintains predictive value in African American men. J Urol. 2018;199(6);1459-1463.
Stattin et al. Improving the Specificity of Screening for Lethal Prostate cancer using prostate-specific antigen and a panel of kallikrein markers: a nested case-control study. Eur Urol. 2015;68(2):207-213.
Sjoberg et al. Twenty-year risk of prostate cancer death by midlife prostate-specific antigen and a panel of four kallikrein markers in a large population-based cohort of healthy men. Eur Urol. 2018;73(6):941-948.
Peltola MT, Niemelä P, Väisänen V, et al. Intact and internally cleaved free prostate‐specific antigen in patients with prostate cancer with different pathologic stages and grades. Urology 2011 Apr;77(4):1009.e1.
Steuber T, Vickers AJ, Serio AM, et al. Comparison of free and total forms of serum human kallikrein 2 and prostate‐specific antigen for prediction of locally advanced and recurrent prostate cancer. Clin Chem. 2007 Feb;53(2):233‐40.
Wenske S, Korets R, Cronin AM, et al. Evaluation of molecular forms of prostate-specific antigen and human kallikrein 2 in predicting biochemical failure after radical prostatectomy. Int J Cancer. 2009 Feb 1;124(3):659‐653.