Prostate Specific Antigen Assay Standardization Bias Could Affect Clinical Decision Making

Purpose: Although prostate specific antigen is widely used to detect and manage prostate cancer, many patients and physicians are unaware of which prostate specific antigen assay is being used. Most commercial prostate specific antigen assays are standardized to the WHO 90:10 standard or aligned with the original Hybritech® assay with potentially disparate results. Materials and Methods: A total of 1,916 men participated in a prostate cancer screening study in 2007. On the day of collection prostate specific antigen was tested from the same serum sample using the Access® (Hybritech standard) and ADVIA Centaur® (WHO 90:10 prostate specific antigen standard) assays. We examined the differences between the 2 assays and the effect that this might have on clinical decisions. Results: Median prostate specific antigen was 0.9 and 1.05 ng/ml for the Centaur and Access assays, respectively, representing a 17% difference. Mean prostate specific antigen was 3.45 and 4.79 ng/ml, respectively, representing a 38% difference. Using a prostate specific antigen threshold of 2.5 ng/ml 5% of men would have been recommended to undergo biopsy using the Access but not the Centaur assay. Furthermore, prostate specific antigen differed by greater than 0.4 ng/ml in 26%, greater than 0.75 ng/ml in 14.5% and greater than 2 ng/ml in 4.5% of men in the same sample simply by using the different assays. Conclusions: In our prospective screening population median prostate specific antigen was 17% lower using WHO vs Hybritech based assay standardization. As such, if these assays were instead used on a serial basis in the same patient, this could lead to false acceleration or false deceleration in prostate specific antigen velocity. Thus, the assay may influence the likelihood of prostate biopsy and, thereby, prostate cancer detection.