From the Guidelines
A low percent free PSA with a normal total PSA level suggests an increased risk of prostate cancer and warrants further evaluation. This finding occurs when a higher proportion of PSA is bound to proteins in the blood rather than circulating freely. While your total PSA falls within normal range (typically under 4 ng/mL), the percentage of free PSA (unbound PSA) below 25% raises concern as prostate cancer cells tend to produce more bound PSA than benign tissue 1.
According to the NCCN guidelines, percent fPSA levels less than 10% are clearly associated with a high risk for having prostate cancer, and patients should be encouraged to undergo a biopsy if percent fPSA values fall below this level 1. A negative linear relationship exists between the likelihood of having prostate cancer and percent fPSA values between the levels of 10% and 25% 1.
Some key points to consider:
- The lower the percent free PSA (particularly below 10%), the higher the likelihood of cancer, even when total PSA appears normal 1.
- Other factors that influence this decision include your age, family history of prostate cancer, previous PSA trends, and findings on digital rectal examination.
- This pattern can sometimes occur with benign conditions like prostatitis or BPH, but the risk of cancer should not be ignored 1.
- I recommend discussing this result with your doctor who will likely suggest additional testing such as a prostate MRI, repeat PSA testing in 3-6 months, or possibly a prostate biopsy depending on your risk factors.
It's essential to note that the use of percent free PSA can help decrease the number of unnecessary biopsies, but larger scale, prospective studies are required to corroborate these findings 1. A low percent free PSA with a normal total PSA level is a significant finding that requires careful evaluation and consideration of additional testing.
From the Research
Prostate-Specific Antigen (PSA) and Percent Free PSA
- If Prostate-Specific Antigen (PSA) is within normal limits but percent free PSA is low, it may indicate a higher risk of prostate cancer 2, 3, 4.
- A low percent free PSA value is a promising diagnostic tool for prostate cancer, but its actual role has not yet been established due to varying sensitivity and specificity values 2.
- The percent free PSA value is effective in reducing the rate of unnecessary biopsies in men with total PSA higher than 4 or 10 ng/mL, but it should be interpreted with caution in individual patients 2.
Diagnostic Performance of Percent Free PSA
- Percent free PSA is superior to total PSA in distinguishing primary prostate cancer from benign prostatic hyperplasia (BPH) in patients with total PSA between 2 and 30 ng/mL 2.
- 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 4.
- Chronic prostatitis is not characterized by elevated total PSA concentrations alone but also by a decreased percentage of free PSA, similar to prostate cancer 3.
Risk Assessment and Biopsy Decision
- A lower percentage of free PSA is associated with a higher risk of cancer, and the percentage of free PSA is an independent predictor of prostate cancer 4.
- A 20% decrease in PSA values is associated with a reduced risk of cancer and particularly of high-grade cancer 5.
- A low percentage of free PSA is a strong predictor of later detection of prostate cancer among men with serum levels of total PSA of 4.0 ng/mL or less 6.