Study type: Blood collected in a gold-, red-, or red/gray-top tube; related body system: Immune, Reproductive, and Urinary systems.

Prostate-specific antigen (PSA) is produced exclusively by the epithelial cells of the prostate, periurethral, and perirectal glands. PSA testing may be used in conjunction with the digital rectal examination (DRE) and ultrasound for detection and monitoring of cancer of the prostate. Risk of diagnosis is higher in men of African descent, who are 61% more likely than Caucasian men to develop prostate cancer. Family history and age at diagnosis are other strong correlating factors.

PSA circulates in both free and bound (complexed) forms. A low ratio of free to complexed PSA (i.e., less than 10%) is suggestive of prostate cancer; a ratio of greater than 30% is rarely associated with prostate cancer. PSA velocity (PSAV), the rate of PSA increase over time, is being used to indicate the potential aggressiveness of the cancer in order to identify the appropriate interventions and to monitor the effectiveness of treatment; at least three serial samples are required.

PSA (total, % free, velocity)

For many years, PSA was considered a valuable screening test. However, the test lacks the specificity to distinguish between benign elevations, less serious forms of cancer, and aggressive forms of prostate cancer. PSA has high rates of false-positive and false-negative results. These factors have led numerous men to undergo unnecessary invasive procedures. Approximately 15% to 40% of patients who have had their prostate removed will encounter an increase in PSA. Patients treated for prostate cancer and who have had a PSA recurrence can still develop a metastasis for as long as 8 yr after the postsurgical PSA level increased. The majority of prostate tumors develop slowly and require minimal intervention, but patients with an increase in PSA greater than 2 ng/mL in a year are more likely to have an aggressive form of prostate cancer with a greater risk of death.

Precision medicine provides a technology to predict the progression of prostate cancer, likelihood of recurrence, or development of related metastatic disease. New technology makes it possible to combine data such as analysis of molecular biomarkers and cellular structure specific to the individual’s biopsy tissue, standard tissue biopsy results, Gleason score, number of positive tumor scores, tumor stage, presurgical and postsurgical PSA levels, and postsurgical margin status with computerized mathematical programs to create a personalized report that predicts the likelihood of post-prostatectomy disease progression. Serial measurements of PSA in the blood are often performed before and after surgery.

Prostate Cancer Antigen 3 (PCA3)

The prostate cancer antigen 3 gene (PCA3) is a nucleic acid amplification test performed on a urine sample. The sample is collected after DRE because stimulation of the prostate releases a greater number of prostate cancer cells containing PCA3 into the urinary tract, where they can be collected and measured in the first-catch urine. PCA3 is overexpressed in prostate cancer but not in benign hypertrophy, which assists in determining the need for repeat biopsy in men 50 yr of age or older who have had positive screening tests with one or more negative prostate biopsies.

Prostate Health Index (PHI)

The Prostate Health Index (PHI) is a multimarker strategy being used to improve the positive prediction rate of prostate cancer, especially when PSA levels are considered to be moderately increased (between 4 and 10 ng/mL). The PHI applies information provided by the results of prostate marker blood tests to a mathematical formula and offers additional information for clinical decision making. The three tests used in the formula are the total PSA, free PSA, and p2PSA (an isoform of PSA), wherePHI = p2PSA/(free PSA × total PSA)The PHI is recommended for males age 50 yr and older whose total PSA is between 4 and 10 ng/mL.

4K Score

The 4K Score is recommended only when the PSA result is abnormal and a biopsy is being considered. The results are designed to provide clinical guidance by evaluating a patient’s probability for being at risk to develop prostate cancer in the absence of significant high-risk factors (e.g., family history, prostate cancer positive mutation markers) other than an elevated PSA. The test is a combination of blood biomarker measurements, a patient demographic (date of birth), and patient-specific clinical information provided in a questionnaire to include prior biopsy findings and an optional DRE finding. The biomarkers include the four kallikrein proteins sourced from the prostate gland: total PSA, free PSA, intact PSA, and human kallikrein 2 (hK2). A complex, validated algorithm evaluates the information and determines an individualized risk of finding aggressive prostate cancer (Gleason score 7 or greater) if a prostate biopsy were to be performed. The interpretation also extends the risk determination of metastasis and mortality for up to 20 yr. The patient may need to meet specific conditions to be considered for testing, e.g., be age 40–80 yr, have no previous history of prostate cancer, no invasive urologic procedure or treatment with 5-antireductase inhibitors (dutasteride, finasteride) in the past 6 mo, or no DRE in the past 4 days. There may be other recommendations and restrictions for discussion between the patient and his HCP.

PSA is also produced in females, most notably in breast tissue. There is some evidence that elevated PSA levels in breast cancer patients are associated with positive estrogen and progesterone status.

Important Note: When following patients using serial testing, the same method of measurement should be consistently used.