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Prostate – specific antigen (PSA)

SI UNITS (recommended)

CONVENTIONAL UNITS

(Seminal Enzyme Released by Prostate - Key Marker for Prostate Cancer Screening, Diagnosis, Monitoring & Recurrence)

Synonyms

  • PSA
  • Prostate-specific antigen
  • γ-seminoprotein
  • Kallikrein-related peptidase 3 (KLK3)
  • Total PSA (tPSA)
  • Free PSA (fPSA)

Units of Measurement

  • ng/mL
  • ng/dL
  • ng/100 mL
  • ng%
  • ng/L
  • µg/L

Unit Relationships

1 ng/mL=1000 ng/L1\ \text{ng/mL} = 1000\ \text{ng/L}1 ng/mL=1000 ng/L 1 ng/mL=1 µg/L1\ \text{ng/mL} = 1\ \text{µg/L}1 ng/mL=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}

All units interconvert directly.

Description

PSA is a serine protease enzyme produced almost exclusively by prostate epithelial cells.
Normally, PSA is secreted into seminal fluid; only small amounts enter the bloodstream.

PSA is organ-specific but not cancer-specific, meaning:

  • Elevated PSA → prostate abnormality
  • Cause may be benign or malignant

PSA exists in blood as:

  • Free PSA (fPSA)
  • Complexed PSA (cPSA)
  • Total PSA (tPSA = fPSA + cPSA)

Clinically most testing uses total PSA, with %fPSA used for cancer risk stratification.

Physiological Role

  • Liquefies semen
  • Enhances sperm motility
  • Member of kallikrein protease family

Clinical Significance

HIGH PSA (Most Important Clinical Finding)

Elevated PSA can occur in:

1. Prostate Cancer

PSA >4 ng/mL increases suspicion.
Levels correlate with:

  • Tumor volume
  • Metastasis risk
  • Recurrence risk

2. Benign Prostatic Hyperplasia (BPH)

Most common non-cancer cause.

3. Prostatitis / Infection

Can significantly elevate PSA (10–20+ ng/mL).

4. Prostatic Manipulation

  • DRE (mild)
  • Catheterization
  • Cystoscopy
  • TRUS biopsy (very high)

5. Ejaculation

Raises PSA for 24–48 hours.

6. Aging

PSA gradually increases.

7. UTI / Urinary retention

LOW PSA

  • Normal finding
  • After radical prostatectomy (should be undetectable)
  • On 5-α reductase inhibitors (finasteride/dutasteride) → PSA falls ~50%

Reference Intervals

(Tietz 8E + AUA + NCCN + Mayo + ARUP)

Age-Adjusted Total PSA Ranges

AgeNormal PSA (ng/mL)
40–49 years0 – 2.5
50–59 years0 – 3.5
60–69 years0 – 4.5
70–79 years0 – 6.5

General Screening Cutoff

  • >4.0 ng/mL → abnormal
  • 2.5–4.0 ng/mL → borderline, risk increases with age

Cancer Risk by PSA Level

PSA (ng/mL)Approximate Cancer Risk
<1Very low
1–3Low–moderate
4–10~25% risk
>10>50% risk
>20High risk / metastasis possible

After Prostatectomy

  • PSA should fall to <0.1 ng/mL
  • Any rise → biochemical recurrence

Free PSA (%fPSA) Interpretation

%fPSA=Free PSATotal PSA×100\%\text{fPSA} = \frac{\text{Free PSA}}{\text{Total PSA}} \times 100%fPSA=Total PSAFree PSA​×100

Used when total PSA is 4–10 ng/mL.

%fPSACancer Probability
<10%High risk
10–25%Intermediate
>25%Low risk

Low %fPSA = higher likelihood of prostate cancer.

Diagnostic Uses

1. Prostate Cancer Screening

Men aged 45–75 depending on risk:

  • African ancestry
  • Family history
  • BRCA2 mutation
  • High-risk groups

2. Diagnosis & Risk Stratification

PSA used with:

  • DRE
  • MRI prostate
  • Biopsy
  • Free/total ratio
  • PSA density (PSAD)
  • PSA velocity

3. Monitoring After Treatment

Radical prostatectomy:

  • PSA should become undetectable (<0.1 ng/mL)

Radiation therapy:

  • Nadir PSA +2 ng/mL = biochemical recurrence

4. Monitoring Active Surveillance

Trend over time more important than a single value.

5. Evaluation of BPH & Prostatitis

Analytical Notes

  • Avoid ejaculation for 48 hours before testing
  • Delay PSA measurement for:
    • 6 weeks after prostatitis
    • 1–2 weeks after DRE
    • 4–6 weeks after UTI
    • 6 weeks after biopsy
  • Hemolysis minimal effect
  • 5-α reductase inhibitors cut PSA in half—always double the result

Clinical Pearls

  • PSA is organ-specific, not cancer-specific.
  • Rapid PSA doubling time suggests aggressive cancer.
  • MRI prior to biopsy improves cancer detection.
  • High PSA with normal imaging may still indicate clinically significant cancer.
  • Low %fPSA increases cancer probability even when PSA is borderline.
  • PSA >100 ng/mL almost always indicates metastatic prostate cancer.

Interesting Fact

PSA was originally discovered as a seminal biomarker for forensic identification before becoming one of the most important cancer markers in medicine.

References

  1. Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Tumor Markers & PSA
  2. AUA Guidelines - Early Detection of Prostate Cancer
  3. NCCN Guidelines - Prostate Cancer Detection & Management
  4. EAU Prostate Cancer Guidelines
  5. Mayo Clinic Laboratories - PSA
  6. ARUP Consult - Prostate Cancer Testing
  7. NIH / MedlinePlus - PSA Test

Last updated: January 27, 2026

Reviewed by : Medical Review Board

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