Unit Converter
Prostate‑specific antigen free (Free PSA)
(Unbound Fraction of PSA - Essential for Prostate Cancer Risk Stratification When Total PSA Is Borderline)
Synonyms
- Free PSA
- fPSA
- Unbound PSA
- Non-complexed PSA
- PSA-free fraction
- KLK3 free fraction
Units of Measurement
- ng/mL
- ng/dL
- ng/100 mL
- ng%
- ng/L
- µg/L
Unit Conversion
1 ng/mL=1000 ng/L=1 µg/L1\ \text{ng/mL} = 1000\ \text{ng/L} = 1\ \text{µg/L}1 ng/mL=1000 ng/L=1 µg/L 1 ng/mL=100 ng/dL1\ \text{ng/mL} = 100\ \text{ng/dL}1 ng/mL=100 ng/dL \text{ng%} = \text{ng/dL}
Description
Free PSA (fPSA) represents the fraction of PSA circulating in blood that is not bound to proteins.
Major binding proteins:
- α1-antichymotrypsin (most common)
- α2-macroglobulin
Total PSA (tPSA) = free PSA + complexed PSA.
Free PSA is LOWER in prostate cancer compared to benign causes like BPH.
Therefore, the %free PSA (%fPSA) significantly improves diagnostic accuracy when total PSA is in the “gray zone” (4–10 ng/mL).
Physiological Role
Free PSA has no independent physiological function; it is a degradation product of PSA that leaks into circulation.
Clinical Significance
HIGH Free PSA
Seen in:
- Benign prostatic hyperplasia (BPH)
- Prostatitis / inflammation
- Post-ejaculation elevation
- Older age (less PSA binding)
- Large prostate volume
Higher fPSA → lower cancer risk.
LOW Free PSA
Most significant finding - strongly associated with prostate cancer.
Causes:
- Prostate cancer (adenocarcinoma)
- High-grade lesions
- Larger tumor burden
- Lower PSA binding protein alteration
Low fPSA = high conversion of PSA to bound (complexed) form, typical of malignancy.
Reference Intervals (Total PSA-Dependent)
(Tietz 8E + NCCN + AUA + Mayo + ARUP)
Absolute Free PSA
Varies widely; not interpreted independently.
Ranges usually:
- <0.5 ng/mL (common with low total PSA)
- 0.5–3 ng/mL (in tPSA 4–10 ng/mL range)
% Free PSA (Key Diagnostic Mark)
%fPSA=Free PSATotal PSA×100\%\text{fPSA} = \frac{\text{Free PSA}}{\text{Total PSA}} \times 100%fPSA=Total PSAFree PSA×100
When Total PSA = 4–10 ng/mL
| % Free PSA | Interpretation |
| <10% | High probability of prostate cancer |
| 10–15% | Moderate to high risk |
| 15–25% | Intermediate risk |
| >25% | Low probability of cancer |
When Total PSA >10 ng/mL
%fPSA loses discriminatory value; tPSA alone carries significant risk.
Diagnostic Uses
1. Distinguishing Prostate Cancer from BPH
Best use case.
Low fPSA strongly favors cancer when total PSA is borderline.
2. Reducing Unnecessary Biopsies
%fPSA >25% may help avoid biopsy in selected men.
3. Risk Stratification Before MRI / Biopsy
- Total PSA 4–10 ng/mL
- Normal DRE
→ %fPSA assists decision-making.
4. Monitoring After Treatment
Not routinely used; total PSA preferred.
5. Assessing High PSA with Negative Imaging
Low fPSA → higher suspicion for clinically significant cancer.
Analytical Notes
- Assay must measure both free and total PSA.
- Draw blood before DRE, ejaculation, cystoscopy, or catheterization.
- Hemolysis minimally affects fPSA.
- fPSA unstable-must be processed rapidly or frozen.
- Different assays use different calibrations → %fPSA must be interpreted with lab-specific reference.
Clinical Pearls
- Free PSA proportion is LOWER in prostate cancer-most important point.
- Use %fPSA only when total PSA is 4–10 ng/mL.
- %fPSA is NOT reliable:
- During prostatitis
- After recent ejaculation
- After instrumentation
- During prostatitis
- A prostate MRI is recommended before biopsy when %fPSA is low.
- Family history + low %fPSA = high suspicion, even if PSA is only mildly elevated.
Interesting Fact
Prostate cancer cells produce PSA that binds more tightly to α1-antichymotrypsin-this shift toward the complexed form leaves less PSA in the free form, explaining why free PSA drops in malignancy.
References
- Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - PSA
- AUA Guidelines - Early Detection of Prostate Cancer
- NCCN Guidelines - Prostate Cancer Detection
- EAU Prostate Cancer Guideline
- Mayo Clinic Laboratories - Free PSA
- ARUP Consult - PSA & Free PSA
- NIH / MedlinePlus - PSA Tests