PSA (free and protein bound)

Last edited 07/2020 and last reviewed 09/2022

The most common PSA test measures the total amount of PSA (both free and protein bound) in the blood:

• an alternative test has been used which calculates the ratio of free: total PSA. Free PSA is associated with benign conditions while bound PSA is associated with malignancy. Hence a low ratio (<25%) may be indicative of cancer (1,2)
• evidence suggest that reflex testing with PSA isoforms, such as ratio of free to total PSA (f/tPSA) or complex PSA (cPSA), for men with PSA values <10 ng/mL (known as the diagnostic “grey zone”) could improve specificity and reduce the number of unnecessary biopsies
• triage of men in the “grey zone” with tPSA 2 to 10 ng/ml using PSA isoforms could potentially reduce overdiagnosis and maintain a high cancer detection rate

Free/total PSA is of no clinical use if total serum PSA is > 10 ng/mL or during follow up of known PCa (3)

Reference:

• Prostate Cancer Risk Management Programme Information for primary care; PSA testing in asymptomatic men. Evidence document. NHS Cancer Screening Programmes, 2016
• Catalona W et al. Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter clinical trial. JAMA 1998; 279 (19): 1542–7
• European Association of Urology 2018. Guidelines on Prostate Cancer.