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cPSA or PSA Free

Prostate Cancer Awareness Week ( has compiled information on a follow-up test for men who have a 2.5 PSA or higher, used prior to a biopsy. The PSA Free (Prostate Specific Antigen, Free and Total includes: PSA-Free, PSA, Free PSA/PSA Ratio.) is one of at least six different ways to look at serum PSA: total PSA, free PSA, age-adjusted PSA, ethnically adjusted PSA, PSA velocity and PSA density.

Diagnosing Prostate Cancer
Free PSA

Sources of Information and Basis for Decision
Prostate Cancer & Its Treatment - UCSF Medical Center Prostate Cancer Advocates

Diagnosing Prostate Cancer

For checking a man's prostate, a blood test to determine the prostate-specific antigen (PSA) has been the gold standard of the exam. Now in the past several years, a new reading called free prostate is being used. Just how much more accurate is this than the former PSA, and can it also sometimes be a false positive like the PSA?

Q: It is claimed that the free prostate can more accurately determine the possible presence of cancer. Is this true?

A: Yours is a complicated but important question since prostate cancer is the leading cancer in men, with about 220,000 new cases a year. Patients often have no symptoms and are taken by surprise when a nodule is discovered on exam or a high PSA is found.

William See, MD, Professor and Chief of Urologic Surgery at the Medical College of Wisconsin, explained that there are now at least six different ways to look at serum PSA: total PSA, free PSA, age-adjusted PSA, ethnically adjusted PSA, PSA velocity and PSA density. Each of these has unique characteristics.

Some tests are more sensitive for identifying patients with cancer and others are more specific, meaning that fewer patients without cancer test false positive. Unfortunately, none of the available tests is perfect. All will miss a percentage of cancers (false negative), and all will incorrectly identify some patients who prove not to have cancer (false positive).

Total PSA with a cutoff point above 4 ng/ml is slightly more sensitive for the detection of patients with cancer than a free PSA cut point of less than 25%. The more sensitive the test, the more likely that it is a false positive.

A free PSA measuring at 30%, above the 25% threshold, might suggest avoiding immediate biopsy. The free PSA cutoff point of less than 25% is more specific for a diagnosis of cancer and avoids the need for biopsy in about 20% of patients who would otherwise undergo this procedure based upon total PSA alone. Determining the risk of a given patient harboring prostate cancer is not always easy and involves more than just going by one PSA value.

Source: Dr. Rebekah Wang-Cheng is a former Professor of Medicine at the Medical College of Wisconsin. Her medical advice column, which answers health-related questions from readers, also appeared in the Milwaukee Journal-Sentinel.



Prostate-specific antigen (PSA) is a glycoprotein (molecular weight 30,000-34,000 daltons) having a close structural relationship to glandular kallikrein. It has the function of a serine protease.

The proteolytic activity of PSA in blood is inhibited by the irreversible formation of complexes with proteinase inhibitors such as alpha-1-antichymotrypsin, alpha-2-macroglobulin and other acute phase proteins. In addition to being present in these complexes, PSA is also present in blood in the free form, but is proteolytically inactive.

PSA tests lack sufficient sensitivity and specificity to be considered ideal or absolutely diagnostic for screening or early detection because PSA is not specific for prostate cancer. PSA is organ specific, being produced primarily by prostatic secretory epithelium, but has long been known to be elevated in non-malignant conditions such as benign prostatic hyperplasia (BPH). A number of studies have found that the % free PSA was significantly lower in patients having prostate cancer than those with benign disease or normal controls. The ratio fPSA/tPSA has been demonstrated to improve the sensitivity and specificity in patients with tPSA values in the "gray zone" of 4-10 ng/ml.

An equimolar tPSA determination is the prerequisite for reliable ratios.

In patients receiving therapy, particularly hormone withdrawal therapy, the fPSA/tPSA ratio cannot be utilized to differentiate prostate hyperplasia from cancer of the prostate. Combining tests from different manufacturers to determine tPSA and fPSA can produce erroneous values, since total PSA tests may be standardized by differing methods or detect free PSA to differing degrees.

The Elecsys free PSA immunoassay is indicated for measurement of fPSA in conjunction with the Elecsys total PSA assay to develop a ratio of fPSA to tPSA (%fPSA). This ratio is useful when used in conjunction with the Elecsys Total PSA test as an aid in distinguishing prostate cancer from benign prostatic conditions in men age 50 years or older who have a digital rectal examination (DRE) that is not suspicious for prostate cancer and an Elecsys total PSA value in the range 4-10 ng/ml. Prostate biopsy is required for the diagnosis of prostate cancer. The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Roche Elecsys 1010 and 2010 immunoassay analyzers.

Test Limitations:

The assay is unaffected by indexes of icterus <65 mg/dl, hemolysis <1000, lipemia <1500 mg/dl and biotin < 60 ng/ml. In patients receiving therapy with high biotin doses (i.e. > 5mg/day) no sample should be taken until at least 8 hours after the last biotin administration.

In vitro tests were performed on 28 commonly used pharmaceuticals. Only flutamide at therapeutic daily dosage levels resulted in slightly depressed free PSA values.

As with all tests containing monoclonal mouse antibodies, erroneous findings may be obtained from samples taken from patients who have been treated with monoclonal mouse antibodies or have received them for diagnostic purposes. Elecsys free PSA contains additives which minimize these effects.

In rare cases, interference due to extremely high titers of antibodies to streptavidin can occur.

There is no high-dose hook effect for free PSA concentrations up to 15,000 ng/ml.

No influence was observed from rheumatoid factor (up to 1500 U/ml).

For diagnostic purposes, the Elecsys free PSA findings should always be assessed in conjunction with the patient's medical history, clinical examination and other findings.

Methodology: Electrochemiluminescence Immunoassay
Source: handbook/test2002.html

Free PSA

Prostatic Specific Antigen (PSA) is glycoprotein tumor marker found in blood serum. It is used in the early detection and management of prostate cancer. PSA exists in several forms in serum and is predominantly bound to proteins in the blood. One form of PSA, free PSA, is not bound. The measurement of the different forms of PSA is said to help discriminate between prostate malignancy and benign prostatic disease. The percent of free PSA is a ratio of non-bound low molecular weight PSA and total PSA. Increased values of free PSA to total PSA (fPSA/PSA) indicate benign prostatic disease.

PSA (84153) testing is considered reasonable and necessary when reported with any of the diagnoses/conditions listed in the ICD-9-CM Codes that support medical necessity.

Free PSA (84154) testing is considered reasonable and necessary in patients in the following categories:

Most often, percent free PSA will be used clinically to reduce the number of patients undergoing prostate biopsy for suspected cancer with a minimal loss of sensitivity in detecting prostate cancer. Males with a total PSA in an intermediate range of 4-10 ng/ml are the group, which will usually benefit from the information provided by the test. If the patient’s percent free PSA is found to be within the reference range, a biopsy may be deferred with minimal risk of missing an early prostate cancer; if percent free PSA is found to be out of your facility’s reference range, biopsy may be clinically indicated. Note that total PSA levels above 10 ng/ml will require biopsy because the risk of prostate cancer is high.

A second useful application for the ratio of free/total PSA values is to discriminate between patients with prostate cancer who are responding to treatment utilizing luteinizing-hormone-releasing-hormone (LH-RH) in contrast to the patient escaping, fluctuating, or not responding to hormone ablation.

Note that prostatic cancer incidence and mortality increase with age; 75% of men with a new diagnosis or prostate cancer are over age 65.

Also note that during the late 1980’s prostate cancer incidence rose sharply, possible attributable to the widespread use of PSA testing. Tumors were detected earlier than they would have been prior to PSA testing. Since 1992, rates have been declining toward incidence levels prior to the widespread use of PSA testing.

Approximately 10% of patients tested for total PSA will need to be tested for percent free PSA. However, this represents 35% of the patients who undergo diagnostic prostate biopsy. Studies show that if these men whose total PSA levels were between 4 and 10 ng/ml had biopsies deferred (pending a normal digital rectal examination and a percent free PSA within reference range) negative biopsies could be reduced by twenty percent.

Percent free PSA as stated in Indications section may also be used as a guide for decisions about re-biopsy. Initial biopsies miss twenty percent of prostate cancers. The percent free PSA helps identify high-risk patients who need repeat biopsies.

Sources of Information and Basis for Decision


Additional Free PSA Reference Points as outlined by the Oregon Medical Laboratories

For men with a Total PSA between 4.1 and 10.0 ng/mL: 

A free PSA % decision points of 24% or less will detect 95% of prostate cancers by biopsy. Source: Vashi & Oesterling: Mayo Clin Proc 1997; 72:337-344

The above decision point of 24% is supported by the fact that the probability of prostate cancer is high (63 +/- 9%) when the free PSA % is < 10% and the probability of prostate cancer is low (2 +/- 3%) when the free PSA % is >26%.

For men with a total PSA between 3.0 and 4.0 ng/mL:

A free PSA % decision point of 19% or less will detect 44% of prostate cancers by biopsy when the total PSA is between 3.0 and 4.0 ng/mL Vashi & Oesterling: Mayo Clin Proc 1997; 72:337-344

The above decision point of 19% is supported by the fact that the probability of prostate cancer is high (59%) when the free PSA % is <19% and the probability of prostate cancer is low (15%) when the free PSA % is >19%.

NOTE: The free PSA % decision points listed above for total PSA between 3.0 and 4.0 ng/mL are not validated and may not apply for total PSA values below 2.5 ng/mL.

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