From the Guidelines
A low percent free PSA with a normal total PSA level is a significant indicator of increased risk for prostate cancer, necessitating further evaluation and discussion with a healthcare provider. This is because a lower percentage of free PSA (typically considered low when under 25%) can be a more sensitive indicator of potential malignancy than total PSA alone 1. When total PSA is within normal limits but percent free PSA is low, it suggests that a higher proportion of PSA is bound to proteins in the blood, which is more commonly associated with prostate cancer cells 1.
The NCCN guidelines recommend using percent free PSA as an alternative in managing patients with normal digital rectal exams (DREs) and total PSA levels between 4 and 10 ng/mL, especially if there's a contraindication to biopsy 1. However, percent free PSA levels less than 10% are clearly associated with a high risk for having prostate cancer, and patients with such levels should be encouraged to undergo a biopsy 1. The relationship between percent free PSA and the likelihood of having prostate cancer is inversely related, with lower percent free PSA values indicating a higher risk of cancer 1.
Given this information, if your PSA is within normal limits but your percent free PSA is low, you should discuss this result with your doctor, who may recommend additional testing such as a prostate biopsy, MRI of the prostate, or newer biomarker tests like the Prostate Health Index or 4Kscore 1. Regular follow-up is essential, as this finding represents an important risk factor even when total PSA appears normal. It's also important to note that the interpretation of PSA results can be complex and may be influenced by various factors, including the use of 5-alpha-reductase inhibitors, which can suppress PSA production 1.
Key points to consider:
- Low percent free PSA with normal total PSA indicates increased risk of prostate cancer.
- Percent free PSA levels less than 10% are associated with a high risk of prostate cancer.
- Further evaluation and discussion with a healthcare provider are necessary.
- Additional testing such as biopsy, MRI, or newer biomarker tests may be recommended.
- Regular follow-up is essential due to the increased risk associated with low percent free PSA.
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.