The complexity of PSA interpretation in clinical practice

Prostate specific antigen (PSA) is central to the diagnosis of prostate cancer. Laboratories quote cut-off reference ranges for PSA but values within these boundaries do not equate with an absence of cancer nor do levels above the range equate with its presence. Convention places the cut-off value at 4 μg/L when calibrated to the Hybritech immunoassay technology and 3.0 or 3.1 μg/L if the PSA methods are calibrated to the WHO IRP 96/670 standard. The prevalence of prostate cancer in screened normal men over 55 years of age with PSA values less than 4 μg/L (Hybritech method) is 10.1% at a PSA of 0.6–1.0 μg/L. About 12.5% of these will be high grade. Two major randomised trials reported on PSA screening. The European trial (ERSPC) reported a risk reduction for prostate cancer death of 21% in the screened group but the US PLCO trial found no benefit. PSA results depend on calibration and there is a 22% difference between the older Hybritech and newer WHO standardisation. Biological variation in PSA is a geometric mean of 7.3%. External quality assessment schemes show wide variation in the performance of PSA analysis. Neither the American College of Physicians nor the UK National Health Service recommends screening except when there is increased risk through family history or ethnicity. Laboratories should detail their method calibration in each report and clinicians should be alerted to the potential misclassification of patients through PSA variation.