Prostate cancer screening through routine measurement of serum prostate-specific antigen (PSA) has been mired in controversy since its inception in the late 1980s. After years of campaigns encouraging men to know your PSA, the US Preventive Services Task Force in 2012 gave PSA testing a D-rating on the basis of data showing little or no benefit to aggressively diagnosing and treating early-stage prostate cancer 2,3 and evidence of significant harms from biopsy and treatment. In 2017, this was revised to a C-rating 4 on the basis of European randomized trials showing modest survival benefits 5-7 and a mitigation of harm through the increasing use of active surveillance for low-risk disease. 8 Adding to this controversy is the heavy burden of prostate cancer in Black men, for whom cancer incidence and death rates are much higher, and more rather than less screening seems most appropriate. 9 Furthermore, Asian, Black, and Hispanic men remain under-represented in most clinical trials, including prostate cancer screening.Key to the PSA controversy is its poor performance as a screening tool, with a specificity of approximately 25% and a sensitivity of 85%, resulting in nearly 1.4 million prostate biopsies performed each year in the United States to diagnose approximately 300,000 cases. 9,10 Complications of prostate biopsies, including urinary tract infections, pain, bleeding, psychological distress, and overdiagnosis and overtreatment of indolent cancers, 4,11,12 have provided impetus for the development of ancillary tests to blunt the harms of PSA testing. These tests help identify men at low risk for clinically significant prostate cancer (csPCa; defined as >Grade group 2 or Gleason grade 3 1 4 5 7), who have a low risk for prostate cancer mortality 13 such that they can be safely excluded from biopsy. In the article that accompanies this editorial, Vigneswaran et al 1 tested the performance of Stockholm3, a reflex test performed in men with a screening PSA level of ≥4 ng/mL, in a prospective multicenter observational trial in 2,129 men, of which 350 were Asian (16%), 505 were Black (24%), 305 were Hispanic (14%), and 969 were non-Hispanic or non-Latino and White (46%, 969). The Stockholm3 test measures PSA, free PSA, KLK2, GDF15, and PSP94 serum protein levels; a polygenic risk score calculated from over 100 germline risk SNPs; the HOXB13 G84E germline variant; and clinical parameters including age, first degree family history of prostate cancer (if available), and history of a previous prostate biopsy. 14,15 In the overall cohort, the Stockholm3 test resulted in a predicted 48% decrease in biopsies while maintaining sensitivity for identifying csPCa. Importantly, the test performance was maintained in all racial and ethnic groups, maintaining a high sensitivity for csPCa in Asian, Hispanic, Black, and White patients, with similar reductions in the need for biopsies across all groups. The SEPTA study provides crucial evidence of validity in multiple racial and ethnic groups and will bolster arguments for broader a...
