Carter et al. introduced the concept of PSAV in 1992, performing multiple PSA measurements on serum samples obtained from men between 7–25 years prior to histological diagnosis or exclusion of PC; they found that while absolute PSA levels did not significantly differ between men with BPH and PC, the rate of change of PSA was significantly greater in those subjects with PC. This evidence concerns the gene KLK3 and pachyonychia congenita.