When a healthcare practitioner is considering a repeat prostate biopsy for a man age 50 or older who has had one or more previous negative biopsies
The prostate cancer antigen 3 (PCA3) test detects genetic material (messenger RNA (mRNA)) that is produced only by the prostate. The protein PCA3 and its associated mRNA are present at low levels in normal prostate tissue. PCA3 is present in increased amounts (over-expressed) in about 90% of prostate cancers. Prostate specific antigen (PSA) is also produced in increased amounts by prostate cancers but can be increased in a number of benign conditions as well.
This test measures PCA3 mRNA and PSA mRNA in the first urine sample collected following a digital rectal exam (DRE). Laboratories report a score based on the ratio of PCA3 mRNA to PSA mRNA called the PCA3 score.
Prostate cancer is the uncontrolled growth of cells in the prostate, a small gland that encircles the urethra in men. Some men may choose to undergo screening for prostate cancer using a PSA blood test. An increased PSA level is associated with an increased risk of prostate cancer, but PSA can also be increased with benign prostatic hyperplasia (BPH), prostatitis, infection, and a variety of other temporary conditions.
Diagnosis of prostate cancer requires performing a prostate biopsy and identifying cancer cells under the microscope. This biopsy may be done after an increased PSA result and/or an abnormal DRE. The accuracy of biopsies depends on the number of tissue samples and the sites from which they are taken. Since the biopsy takes small tissue samples, and since PSA is not cancer-specific, the initial biopsy is often negative.
A negative initial biopsy may leave the healthcare practitioner questioning whether the patient is truly cancer-free or if the cancer has been missed. Concerns over missing clinically significant cancer may prompt additional biopsies, especially if a repeat PSA is still elevated or has increased. However, each biopsy has potential complications, such as discomfort, blood in the urine (hematuria) or semen, rectal bleeding, difficulty urinating, infection, and in rare cases septicemia, so minimizing the number of biopsies performed is also desirable.
The PCA3 test can help determine if a repeat prostate biopsy would likely be positive and whether a man may avoid an unnecessary repeat biopsy. PCA3 is significantly over-expressed with prostate cancer but (unlike PSA) it is not affected by prostatitis or BPH.
How is the test used?
When is it ordered?
The test may be ordered when a man has had an elevated PSA blood test and/or abnormal digital rectal exam (DRE) and one or more previous negative prostate biopsies. It may be ordered when another biopsy would normally be recommended and a healthcare practitioner wants to evaluate the likelihood that the repeat biopsy would be positive.
What does the test result mean?
The PCA3 test result is a ratio of PCA3 mRNA to PSA mRNA that is reported as a score. The laboratory report provides a cut-off number at which the score is considered positive.
The PCA3 test does not provide a definitive answer as to whether a man has a cancer or not. Rather, healthcare practitioners consider the test results in conjunction with other laboratory and clinical data to determine the likelihood that a repeat biopsy will be positive.
A PCA3 score that is less than the laboratory's established cutoff is considered negative and is associated with a decreased likelihood of a positive biopsy.
A PCA3 score that is greater than the laboratory's established cutoff is considered positive and is associated with an increased likelihood of a positive biopsy. Some labs provide a range in which PCA3 is considered positive but with a caution about interpreting results that are close to the cut-off value, due to normal test variability.
About 90% of prostate cancers will over-express PCA3, but the PCA3 result cannot be used to diagnose or completely rule out prostate cancer. It just helps to guide decision-making on performing another biopsy. Prostate biopsy is still the gold standard for diagnosing prostate cancer.
Is there anything else I should know?
Many prostate cancers are slow-growing and not considered clinically significant. A man who has prostate cancer is more likely to live with the condition and die of something else. Prostate cancer may be managed through "watchful waiting" and treated if or when needed. Some prostate cancers, however, are aggressive and can grow and spread throughout the body. Distinguishing between the two can be challenging but is important. In recent years, there has been considerable concern about over-diagnosing and over-treating prostate cancers that are not clinically significant. In part, this is because the treatments carry the potential for significant complications that can impact a man's quality of life, including urinary incontinence and erectile dysfunction.
The medical community has become increasingly conservative about recommending PSA as a screening tool in asymptomatic men (See Screening Tests for Adults (30-49): Prostate cancer and Screening Tests for Adults (50 and Up): Prostate cancer for details on screening recommendations) and are eager to find additional tools that can aid in decision-making. PCA3 is one of these tools.
A wide range of other tests and biomarkers are being investigated.
Can I skip the digital rectal exam (DRE) and just collect a urine sample?
No, the DRE is a very necessary part of the sample collection. The procedure releases prostate cells and PCA3 into the urine, where it can be detected. This is why it is also important to collect the first amount of urine after the DRE – so the released PCA3 is present in the urine sample.
Can the test be performed in my healthcare practitioner's office?
The DRE will be performed in your healthcare practitioner's office and, most likely, so will the urine collection as it is the first urine collected after the DRE. However, the testing requires specialized equipment and your sample will be sent to a laboratory for testing. Not all labs perform this test, so your sample may be sent to a reference laboratory.
Will PCA3 testing detect all prostate cancers?