Assessments of PSA Forms and hK2 as Very Early Predictors of Prostate Cancer

Concentrations of prostate-specific antigen (PSA) and human kallikrein 2 (hK2) were investigated in blood samples that had been obtained from men who were diagnosed with prostate cancer (PCa) decades later. The studies were based on a cohort comprising 22,444 men who, in 1974?1986, were early middle aged and represented a non-PCa-screened population. The results clearly demonstrate a very strong correlation between levels of all biomarkers and later PCa diagnosis. Moreover, the PSA forms and hK2 detected in the samples from men who had developed PCa were significantly increased as early as 25 years before diagnosis. Analysis also showed that even a unit increase in total PSA was associated with subsequent diagnosis. This effect of total PSA was decreased among older men (aged 60), whereas hK2 and percent free PSA were less dependent on age. A significant relationship was found between levels of hK2 and time to diagnosis. However, adding the annual rate of increase in PSA to a predictive model did not improve the accuracy compared to that achieved using a single PSA value. Finally, reanalysis of the data on the men with clinically significant disease (i.e., metastases or ? stage T3 PCa at diagnosis) showed that 93% of those individuals were among the 20% of the subjects with the highest PSA levels. Accordingly, the present findings demonstrate that all men should undergo PSA testing before the age of 50, but only the 20% found to have the highest PSA levels should immediately be assigned to further screening.