What is the significance of free Prostate-Specific Antigen (PSA)?

From the Guidelines

Free Prostate-Specific Antigen (PSA) is a significant diagnostic tool in distinguishing between prostate cancer and benign prostate conditions, particularly when total PSA levels are mildly elevated. The significance of free PSA lies in its ability to help determine the need for a prostate biopsy, especially in cases where total PSA levels are between 4-10 ng/mL. A lower percentage of free PSA (less than 25%) is associated with a higher risk of prostate cancer, while a higher percentage (greater than 25%) typically indicates benign conditions like benign prostatic hyperplasia (BPH) 1. The free PSA test works by measuring the percentage of PSA that circulates freely in the blood compared to the total PSA level, with prostate cancer cells tend to produce PSA that binds to proteins in the blood, while benign prostate cells produce more of the free, unbound form. Some key points to consider when evaluating the significance of free PSA include:

• The level of PSA correlates with the risk of prostate cancer, with higher levels conferring a greater likelihood of prostate cancer 1
• Biomarkers like percent free PSA can improve the specificity of detection, but are not recommended as first-line screening tests 1
• The decision to screen for prostate cancer using the PSA test should be based on a discussion of the benefits and harms of screening, the patient's general health and life expectancy, and patient preferences 1
• Clinicians should not screen for prostate cancer in men who do not express a clear preference for screening, and should document patient preferences in the medical record 1
• The goal of screening for prostate cancer is to identify an undiagnosed condition for which an effective treatment is available, and timely treatment can lead to improved clinical outcomes 1. Some of the benefits of using free PSA include:
• Helping to reduce unnecessary biopsies in men with borderline PSA results
• Providing additional information to help determine the need for a prostate biopsy
• Improving the specificity of detection for prostate cancer However, it's also important to consider the potential harms of screening, including:
• False-positive results, which can lead to anxiety and unnecessary biopsies
• Overdiagnosis, which can lead to unnecessary treatment and associated adverse effects
• The potential for screening to detect cancers that would never have caused symptoms in the patient's lifetime. Overall, the significance of free PSA lies in its ability to provide additional information to help diagnose and manage prostate cancer, while also considering the potential benefits and harms of screening.

From the FDA Drug Label

In clinical trials, dutasteride reduced serum PSA concentration by approximately 50% within 3 to 6 months of treatment. The free-to-total PSA ratio (percent free PSA) remains constant, even under the influence of dutasteride If clinicians elect to use percent free PSA as an aid in the detection of prostate cancer in men receiving dutasteride, no adjustment to its value appears necessary.

The significance of free Prostate-Specific Antigen (PSA) is that it remains a constant and reliable indicator for the detection of prostate cancer, even in patients taking dutasteride.

• The free-to-total PSA ratio is not affected by dutasteride treatment.
• This means that no adjustment is needed when using percent free PSA to aid in the detection of prostate cancer in men receiving dutasteride 2.

From the Research

Significance of Free Prostate-Specific Antigen (PSA)

• Free PSA is a valuable tool in the early detection of prostate cancer, as it can help improve the specificity of PSA testing 3, 4, 5, 6.
• The measurement of free PSA can help distinguish between prostate cancer and benign prostatic hyperplasia (BPH), reducing the number of unnecessary biopsies 3, 5, 6.
• A low percent free PSA (< 10%) is a significant predictor of prostate cancer, even after two or more negative prostate biopsies 3.
• The addition of percent free PSA to total PSA can improve the prediction of clinically significant prostate cancer and fatal prostate cancer 4.
• Free PSA can be used to risk-stratify screening and decrease unnecessary prostate biopsies 4.

Diagnostic Performance of Free PSA

• The diagnostic performance of free PSA is enhanced when methodological variability is reduced, particularly in men with low total PSA 5.
• Free PSA is superior to total PSA in distinguishing primary prostate cancer from BPH in patients with total PSA between 2 and 30 ng/mL 5.
• 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 5.
• However, the post-test probability of the disease is relatively low in younger patients with total PSA within the normal range, and the percent free PSA value should be interpreted with caution 5.

Limitations of Free PSA

• Chronic inflammation of the prostate can affect the ratio of free-to-total PSA, making it an unspecific means to distinguish among prostate cancer, chronic prostatitis, and BPH 7.
• Patients with prostate cancer and chronic prostatitis have a significantly lower percentage of free PSA than those with BPH, making it challenging to differentiate between prostate cancer and chronic prostatitis using free PSA alone 7.