A 65-year-old man has PSA of 18 ng/mL. To distinguish benign prostatic hyperplasia (BPH) from prostate cancer, the free-to-total PSA ratio is measured. In which direction does this ratio shift in prostate cancer compared to BPH?

• A Free PSA is proportionally higher in prostate cancer, raising the free/total ratio above 25%
• B Total PSA rises but the free/total ratio remains unchanged in cancer
• C Free PSA is proportionally lower in prostate cancer, reducing the free/total ratio below 10–15% ✓
• D PSA is entirely bound to alpha-2 macroglobulin in cancer, not detectable as free fraction

Explanation

In prostate cancer, more PSA is complexed to alpha-1-antichymotrypsin and alpha-2-macroglobulin, leaving a smaller proportion circulating as free (uncomplexed) PSA. A free/total PSA ratio <10–15% is associated with higher probability of malignancy and warrants biopsy. In BPH, PSA released from hyperplastic but non-malignant glands is proportionally more free (>25%). This test helps avoid unnecessary biopsies when total PSA is in the 4–10 ng/mL grey zone. PSA is measurable as free form in both conditions; it is not entirely bound by alpha-2-macroglobulin.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.