PSA, % Free

Other names: PSA, % Free, PSA, FREE

check icon Optimal Result: 25 - 50 %.

Prostate-specific antigen (PSA) is a protein produced almost exclusively by prostate tissue. In the bloodstream, PSA exists in two main forms:

  • Free PSA: PSA that circulates unbound

  • Bound PSA: PSA attached to carrier proteins

Total PSA represents the sum of both forms.
PSA, % Free expresses how much of the total PSA is unbound and is calculated as:

(Free PSA ÷ Total PSA) × 100

This ratio provides important diagnostic insight because prostate cancer tends to produce proportionally more bound PSA, resulting in a lower % free PSA, whereas benign conditions typically release more free PSA.

Why PSA, % Free Matters

Total PSA alone is not cancer-specific. PSA levels can rise due to aging, prostate enlargement, inflammation, infection, recent ejaculation, or prostate manipulation. This limitation is most evident when total PSA falls between 4–10 ng/mL, a range often referred to as the diagnostic gray zone.

In this setting, PSA, % Free significantly improves risk stratification and helps determine who may benefit from further evaluation or prostate biopsy.

General Interpretation

  • Lower % free PSA → Higher likelihood of prostate cancer

  • Higher % free PSA → More consistent with benign prostate conditions

Cancer Risk by % Free PSA (Total PSA 4–10 ng/mL, Non-suspicious DRE)

Risk increases as % free PSA decreases and also rises with age.

  • ≤10%: Highest cancer probability

  • 10–25%: Intermediate risk

  • >25%: Lowest cancer probability

Large clinical studies (including Catalona et al., JAMA) have shown that men with % free PSA above 25% may often avoid biopsy, while those below 10% have a substantially higher likelihood of prostate cancer.

When Total PSA Is Normal but % Free PSA Is Low

Although less common, this pattern can occur.

Possible explanations include:

  • Very early-stage prostate cancer

  • Biological or assay variability

  • Transient inflammation

In these cases, clinicians may recommend repeat testing, digital rectal examination (DRE), prostate MRI, or close monitoring of PSA trends rather than immediate biopsy.

PSA Trends Matter

Beyond a single measurement, PSA kinetics provide additional insight:

  • PSA velocity (rate of rise over time)

  • PSA doubling time

Rapid increases or shortening doubling times raise concern and may warrant further evaluation, even if absolute PSA values are modest.

Important Limitations

  • % free PSA is most useful when total PSA is between 4–10 ng/mL

  • At very low total PSA levels (<1–2 ng/mL), % free PSA may not be technically reliable or clinically meaningful

  • Results must always be interpreted in context of age, family history, race, symptoms, and prior PSA values

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What does it mean if your PSA, % Free result is too low?

Interpreting PSA Results: Key Factors

Total PSA

PSA levels naturally increase with age, and different age groups have different expected ranges (ng/mL):

  • Age ≤49: 0.0–2.5

  • Age 50–59: 0.0–3.5

  • Age 60–69: 0.0–4.5

  • Age ≥70: 0.0–6.5

A value above the age-adjusted range may suggest an increased risk of prostate cancer, but it is not diagnostic. Total PSA can also rise due to benign prostatic hyperplasia (BPH), prostatitis, recent ejaculation, or even catheterization. Because total PSA alone is nonspecific, clinicians use additional measures—especially free PSA and % free PSA—to refine interpretation.


Free PSA and the Free-to-Total PSA Ratio

PSA circulates in two forms:

  • Free PSA: unbound

  • Bound PSA: attached to proteins

The % free PSA is calculated as:
(free PSA ÷ total PSA) × 100

How to interpret it:

  • Higher % free PSA: More consistent with benign conditions

  • Lower % free PSA: Suggests a higher likelihood of prostate cancer

Typical interpretive thresholds:

  • 0–10%: Risk of cancer can be as high as ~50–60%

  • >25%: Risk drops to roughly 8–15% (depends on age)

These values help guide whether a biopsy is appropriate, especially when total PSA is in the gray zone of 4–10 ng/mL.


When Total PSA Is Normal but % Free PSA Is Low

This combination can be confusing, but it does occur.

What it means:

  • Normal total PSA: Typically suggests no significant prostate disease

  • Low % free PSA (especially <10–15%): Suggests increased production of bound PSA, which may occur in prostate cancer—even before total PSA rises

Possible explanations:

  • Very early-stage prostate cancer

  • Biological variation

  • Assay variability

  • Temporary effects (e.g., inflammation)

Recommended next steps:

  • Repeat PSA in several weeks or months to look for trends

  • Digital rectal exam (DRE)

  • MRI or targeted imaging

  • Biopsy, if clinical suspicion remains elevated

Context always matters. Family history, race, age, prior PSA history, and symptoms must be included in the assessment.


PSA Kinetics

How PSA changes over time can be as important as the absolute value:

  • PSA Velocity: Speed of change; a rapid rise raises concern

  • PSA Doubling Time: Faster doubling times suggest more aggressive disease

These metrics are especially useful after cancer treatment or in active surveillance programs.


Non-Cancer Causes of Elevated PSA

Several benign conditions can raise PSA:

  • BPH (benign prostate enlargement)

  • Prostatitis or infection

  • Recent ejaculation

  • Prostate manipulation (e.g., catheterization)

  • Long bike rides (less common but documented)

These must be considered before assuming cancer risk.


Age-Specific Cancer Risk Using % Free PSA

For men with non-suspicious DRE and total PSA between 4.0–10.0 ng/mL
(Roche E602 immunoassay system, 2015)

% Free PSA 50–59 yrs 60–69 yrs ≥70 yrs
≤10% 49.2% 57.5% 64.5%
11–18% 26.9% 33.9% 40.8%
19–25% 18.3% 23.9% 29.7%
>25% 9.1% 12.2% 15.8%

Interpretation:

  • ≤10% free PSA: Highest cancer probability

  • >25% free PSA: Lowest probability

  • Risk increases with age in every category

Note: In very low total PSA ranges (<1–2 ng/mL), calculation of % free PSA may not be technically possible or clinically meaningful.

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