Prostate-specific antigen (PSA) is a kallikrein-related serine protease. In prostate cancer, PSA is used as a tumour marker. PSA exists in two forms: free PSA and complexed PSA (bound to alpha-1-antichymotrypsin). The clinical utility of the free/total PSA ratio is:

• A A high free/total PSA ratio (>25%) is associated with higher risk of prostate cancer in the 4-10 ng/mL grey zone
• B A low free/total PSA ratio (<15%) is associated with higher risk of prostate cancer in the 4-10 ng/mL grey zone ✓
• C Free PSA rises selectively in metastatic prostate cancer, predicting bone involvement
• D Complexed PSA alone is used to diagnose prostate cancer; free PSA is not clinically useful

Explanation

In the PSA grey zone (4–10 ng/mL), total PSA alone has poor specificity for prostate cancer vs. benign prostatic hypertrophy (BPH). In BPH, more PSA is secreted in the free form, resulting in a higher free/total PSA ratio. In prostate cancer, PSA is more commonly complexed with alpha-1-antichymotrypsin (or alpha-2-macroglobulin), reducing the free fraction. Therefore, a low free/total PSA ratio (<10–15%) is associated with higher probability of prostate cancer and may indicate need for biopsy in this grey zone. A high free/total PSA ratio (>25%) more likely indicates BPH, reducing unnecessary biopsies.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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Written and medically reviewed by the StethoPrep medical team.