Implementation of 4Kscore as a Secondary Test Before Prostate Biopsy: Impact on US Population Trends for Prostate Cancer.

Prostate cancer screening using prostate-specific antigen (PSA) reduces prostate cancer mortality at the cost of unnecessary prostate biopsy, overdiagnosis, and overtreatment. Several secondary tests have been developed to restrict biopsy to men at the greatest risk of high-grade disease. 4Kscore is a widely used secondary test that has been shown to reduce biopsy rates by approximately two-thirds in routine clinical practice. We estimated how 4Kscore implementation has affected cancer trends in the US population. We combined data from the US validation study of 4Kscore with data from the diagnostic test impact study, using a basis of 70 000 on-label 4Kscore tests performed annually. We estimate that each year, 4Kscore leads to 45 200 fewer biopsies and 9400 fewer overdiagnoses of low-grade cancer, at the cost of delayed diagnosis of high-grade prostate cancer for 3450 patients, of whom two-thirds have International Society of Urological Pathology grade group 2 disease. These findings need to be taken into consideration when studying epidemiologic trends in prostate cancer. They also suggest that high levels of overdiagnosis and overtreatment are not inevitable characteristics of PSA screening, but can be mitigated by additional tests. Patient summary: We estimate that use of a test called 4Kscore to predict the probability that a patient has high-grade prostate cancer has significantly reduced the number of unnecessary biopsies and overdiagnosis of low-grade cancer in the USA. These decisions may result in delayed diagnosis of high-grade cancer in some patients. 4Kscore is a useful additional test in the management of prostate cancer.