Other trials that evaluated new biomarkers for screening have used a PSA cutoff below which the new biomarker was not applied.23,24 The early PSA studies25,26 provided historic evidence that a threshold of 3 ng/mL will miss clinically significant cancers, and in the UK Cluster Randomized Trial of PSA Testing for Prostate Cancer,4 68 (46.6%) of 146 men dying of prostate cancer had a PSA level less than 3 ng/mL. This evidence concerns the gene KLK3 and cancer.