Examples of screening clinical trials with no reduction in cause-specific mortality, in which we can examine whether the negative outcome might have been predicted earlier by the surrogate endpoint, include negative trials of screening of proven benefit (listed in the preceding paragraph) and trials of lung (x-ray),24 ovary (ultrasound and CA-125 or multimodal screening),25 and prostate (prostate-specific antigen [PSA]) cancer.26 For prostate cancer, there are some trials showing a reduction in mortality, and others that failed to show such an effect. This evidence concerns the gene KLK3 and prostate cancer.