The Science Behind 4Kscore®
The 4Kscore® Test is a follow-up blood test after an abnormal PSA or digital rectal exam (DRE) to assess the risk of aggressive prostate cancer. The 4Kscore® Test combines measurements of four prostate-specific biomarkers along with patient clinical information in an algorithm to accurately predict a man’s risk for aggressive prostate cancer. Understanding relative risk for 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 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 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 US based validation study of the 4Kscore® Test in 1012 men examined the accuracy of the test to predict the risk of high-grade cancer on biopsy and the contributions of the different test components. The Area Under the Curve (AUC) for 4Kscore® Test was 0.82 compared to 0.74 for a PSA-based risk calculator. Intact PSA and 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 risk 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
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 risk 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):659‐63.