From the Guidelines
A normal free Prostate-Specific Antigen (PSA) level is typically considered to be above 25% of the total PSA. This means that if your total PSA is 4 ng/mL, a normal free PSA would be at least 1 ng/mL or higher. Free PSA is a portion of the total PSA that circulates unbound in the bloodstream. The free PSA percentage is calculated by dividing the free PSA by the total PSA and multiplying by 100. This measurement is particularly useful when total PSA levels are mildly elevated (between 4-10 ng/mL). Lower percentages of free PSA (below 25%) are associated with a higher risk of prostate cancer, while higher percentages typically suggest benign conditions like prostate enlargement.
Key Points to Consider
- The FDA approved the use of percent free PSA for the early detection of prostate cancer in men with PSA levels between 4 ng/mL and 10 ng/mL 1.
- A 25% free PSA cutoff detected 95% of prostate cancers while avoiding 20% of unnecessary prostate biopsies 1.
- The interpretation of free PSA results should always be done by a healthcare provider who can consider individual risk factors and clinical context.
- Free PSA is not a cancer-specific marker, and therefore most men with elevated PSA levels do not have prostate cancer 1.
- Total PSA levels >10 ng/mL confer a greater than 67% likelihood of prostate cancer 1.
Clinical Application
In clinical practice, free PSA is used as part of a comprehensive assessment that may include digital rectal examination, total PSA, and other clinical factors to determine the need for further testing such as prostate biopsy. The use of free PSA can help avoid unnecessary biopsies and improve the early detection of prostate cancer. However, it is essential to consider individual risk factors and clinical context when interpreting free PSA results.
Evidence-Based Recommendation
The most recent and highest quality study recommends using a 25% free PSA cutoff for the early detection of prostate cancer in men with PSA levels between 4 ng/mL and 10 ng/mL 1. This recommendation is based on the study's findings that a 25% free PSA cutoff detected 95% of prostate cancers while avoiding 20% of unnecessary prostate biopsies.
From the Research
Normal Free Prostate-Specific Antigen (PSA) Levels
- The normal free PSA level is not explicitly defined in the provided studies, but various cutoffs are suggested for different total PSA ranges 2, 3, 4, 5, 6.
- A cutoff of 25% or less free PSA is recommended for patients with PSA values between 4.0 and 10.0 ng/mL and a palpably benign gland, regardless of patient age or prostate size 2.
- For patients with a total PSA between 2 and 4 ng/mL, a percent free PSA cutoff of 18% to 20% can detect about 50% of cancers while sparing up to 73% of unnecessary biopsies 4.
- A percent free PSA of less than 27% can be useful for detecting early-stage but clinically significant cancers in men with a total PSA value between 2 and 4 ng/mL and normal digital rectal examination (DRE) findings 5.
- A free-PSA level of 25% in patients with total PSA greater than 4.0 ng/ml can detect 97.4% of prostate cancer, with a decrease in negative biopsies of 21% 6.
Free PSA Levels in Different Clinical Scenarios
- In patients with prostate cancer, the median free-PSA level was 8.1% compared to 16.7% in patients with benign prostatic hyperplasia (BPH) 6.
- The median free-PSA levels in patients with prostate cancer according to clinical stage were: 10.1% for T1 N0 M0, 8.1% for T2 N0 M0, 8.4% for T3-4 N0 M0, and 6.1% for T1-4 N1-3 M0-1 6.
- The free PSA levels were not significantly different according to the Gleason score, with median values of 7.7%, 8.7%, and 6.6% for scores between 2 and 4,5 and 7, and 8 and 10, respectively 6.