fPSA

Free PSA (fPSA) is the fraction of prostate-specific antigen in the blood that circulates unbound to proteins. It is measured from the same blood sample as total PSA and is usually reported both as an absolute free PSA concentration and as a percentage of total PSA, known as the %fPSA, calculated as (free PSA / total PSA) × 100.

Clinically, fPSA is used primarily to improve risk assessment in men with elevated total PSA, particularly when PSA falls in the gray zone (roughly 4–10 ng/mL). A lower %fPSA is associated with a higher likelihood of prostate cancer, while a higher %fPSA suggests benign conditions such as benign prostatic hyperplasia. Thresholds are not absolute; commonly cited ranges classify approximately: %fPSA below about 10%–15% indicating greater cancer probability, and above about 25% indicating lower probability, with 10–25% lying in a diagnostic gray area. Laboratory cutoffs can vary by assay and age.

Interpretation of %fPSA should consider several factors, including age, prostate volume, prostatitis, recent procedures, and medication use, as these can influence results. Assay variability and pre-analytical factors can also affect measurements. fPSA testing is intended to reduce unnecessary prostate biopsies and guide decision-making but is not a definitive test for cancer. Biopsy decisions should incorporate total PSA, %fPSA, digital rectal examination findings, imaging (such as mpMRI), and patient preferences.

Related testing includes protocols that combine free PSA with other PSA derivatives, such as the [-2]proPSA isoform used in the Prostate Health Index (PHI), to refine risk assessment further.