Prostate Cancer Blood Tests: PSA, Free PSA, PHI, 4Kscore, and SelectMDx Compared

Beyond standard PSA, several blood-based biomarkers improve specificity for clinically significant prostate cancer, reducing unnecessary biopsies.

1. Total PSA (tPSA)

Measures all PSA forms. Elevated in cancer, BPH, prostatitis, recent ejaculation, catheterization. Limited specificity.

2. Free PSA (fPSA)

Unbound PSA fraction. Lower %fPSA (≤10–25%) increases cancer probability. Used when tPSA 4–10 ng/mL (“gray zone”).

3. Prostate Health Index (PHI)

Formula: ([-2]proPSA / fPSA) × √tPSA. More specific for high-grade cancer (Gleason ≥7) than tPSA or %fPSA alone. FDA-approved for tPSA 4–10 ng/mL.

4. 4Kscore Test

Combines four kallikreins (tPSA, fPSA, intact PSA, hK2) + age, DRE, prior biopsy status → algorithm predicts risk of Gleason ≥7 cancer on biopsy. Validated in multiple cohorts.

5. SelectMDx

Measures urinary mRNA (HOXC6, DLX1) + clinical factors (age, PSA, DRE, prior biopsy) → risk score for high-grade cancer. Non-invasive (urine after DRE).

6. ExoDx Prostate (IntelliScore)

Exosomal RNA (ERG, PCA3, SPDEF) from first-catch urine (no DRE needed). Rules out high-grade cancer.

Clinical Integration

• Used after elevated PSA to decide on biopsy.
• MRI (PI-RADS) increasingly used before/alongside biomarkers.
• Guidelines (NCCN, AUA) support biomarker use in select patients.

Discuss with your urologist which test(s) fit your clinical scenario.