Taking a biopsy of prostate cancer is one of the most widely debated steps to diagnose and treat men with lower urinary tract symptoms.
It is the gold-standard procedure to give men a final diagnosis of prostate cancer and stage the disease.
However, it does have severe side effects and long-lasting health outcomes.
This is especially the case because biopsies are often performed more than once, and they are sometimes an undue risk (3).
Among the side effects of a prostate biopsy, we can have:
- Chronic bleeding of the urinary tract.
- Recurrent urinary infections.
- Chronic urinary pain (1, 2).
Doctors should use every diagnostic tool available before resulting to unnecessary prostate biopsies.
Even so, the PSA test, digital rectal examination, and imaging tests may still give out false positives.
Recent investigations have pointed out that the PCA3 test might soon become the solution to this medical dilemma.
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What is the PCA3 test?
PCA3 rna stands for Prostate Cancer Antigen 3, and it is also known as DD3 (4). It is a gene that is expressed in up to 95% of prostate cancer cells and not in healthy cells.
Thus, it is a useful candidate to detect up to 95% of prostate cancers and distinguish between benign cells and cancer cells (5).
This is an invaluable asset to screen prostate cancer. It provides a quick and painless solution for patients with reasonable suspicion of prostate cancer.
PCA3 is an excellent choice for prostate cancer patients who are not yet full candidates to prostate biopsies or decide not to use this diagnostic tool.
How does it differ from the PSA test?
Patients may have a hard time understanding the difference between the PCA3 test and the PSA test (prostate specific antigen).
They are both antigens, they are useful to diagnose prostate cancer, and their acronyms are similar. However, they are quite different in everything else.
PSA tests require a blood sample, while PCA3 tests are based on urine samples. Even if they are both antigens, one of them requires a relatively cheap technique, while the other is much more expensive.
Moreover, false positives in PCA3 tests are much lower. It also has high sensitivity and specificity to detect real cases of prostate cancer. PSA tests are modified for a high number of causes, including :
- Digital rectal examination of the prostate.
- Using urinary catheters.
- Sexual intercourse.
- Prostatitis.
- Benign prostatic hyperplasia and other benign prostate conditions.
PCA3 will only turn out to be positive in cases of prostate cancer. This is as non-carcinogenic cells do not have this gene activated (6).
What does the PCA3 test measure?
PCA testing uses a technique named polymerase chain reaction (PCR) to make several copies of DNA in a urine sample.
This test is meant to amplify a DNA section. A score is then calculated according to the ratio of mRNA copies of PCA3 to mRNA copies of PSA and then multiplied by 1000.
This sample is to be obtained after a prostatic massage, which is meant to release prostate cells and make them available for testing.
The PCA3 tests determine the presence of a gene segment located in the long arm of chromosome 21 and 22.
Through PCR, it is possible to replicate this antigen massively and detect its presence in a urine sample. Since 95% of cancer cells display this gene, and it is not found in healthy cells, PCA3 is a handy marker of prostate cancer risk (5).
How accurate is a PCA3 test?
The results of a PCA3 test are expressed in PCA3 ratio. Even though there is not a standard way to measure the results, there are safe and unsafe ranges we can consider, according to conclusions by the American Urological Association.
Receiving a result of 0-17 is associated with a significantly lower chance of having a positive biopsy for prostate cancer. It is a negative result, similar to 18-24, which is to be interpreted with more caution.
In some cases, it would be advisable to repeat the PCA testing if the patient’s results are near 24.
24-31 PCA3 ratio is a positive result, but if you have a result close to the lower threshold level, it is better to repeat the test.
More than 31 is a positive result, and in this case, there is a very high chance of having a positive biopsy for prostate cancer (7).
How useful is the PCA3 urine test for prostate cancer?
The importance of the PCA3 urine test for prostate cancer becomes more evident if we look at the statistics.
Prostate cancer is usually less aggressive than other types of cancer. The majority of cases are slowly progressing and with a reduced invasive potential.
Patients with a prostate cancer diagnosis may even die for many other reasons, and not due to prostate cancer, especially in the case of older adults (1).
Despite the efforts to adjust PSA levels according to a baseline, and choosing the most appropriate age for prostate cancer screening, we still have false positives, resulting in patients undergoing unnecessary prostate biopsies.
This is especially the case when there is a “gray zone” in which a high suspicion of prostate cancer is not clear after assessing PSA levels and other screening methods.
For example, we can have a patient with a PSA higher than 3 ng/mL but lower than 5 ng/mL, suspicious symptoms but an unclear rectal examination, not conclusive results in transrectal ultrasound and other imaging studies.
In these cases, we should do something to reduce the number of deaths due to prostate cancer. But this should be achieved without putting the patient through a biopsy and its side effects (1, 2).
That is where PCA3 tests become an invaluable biomarker to reduce the incidence of false negatives and only prescribe biopsies when necessary.
As noted in the previous sections of this article, PCA3 is sensitive and reliable to diagnose prostate cancer. The majority of patients with a positive result will turn out to be positive in their biopsy results as well.
The gray zone we mentioned above is estimated to be composed of up to 25% of high grade prostate cancer, and only advanced diagnostic tests such as PCA3 will be able to contribute to early detection of cancer and determine whether a prostatic biopsy is needed (8).
Even patients with a diagnosed case of prostate cancer may benefit from a PCA3 test for diagnostic accuracy. It can differentiate prostate cancer patients who require a new biopsy and to aid in correlating the case with the Gleason score and other clinical features.
However, is there any downside to using PCA3 as a diagnostic tool for prostate cancer? Are we ever going to replace PSA testing with PCA3 to screen prostate cancer?
How much does it cost?
One of the main concerns about PCA testing is how expensive it is. Compared to the PSA, a PCA3 test is much more costly because it requires another type of testing with more sophisticated technology.
Costs vary depending on each laboratory and your country, but it is usually a minimum of $200 and up to $450.
Additionally, Medicare and most insurance companies do not cover this diagnostic test. Thus, it is not meant as a screening test that should be applied every year to all patients, as it happens with PSA.
It is only used in some instances when doctors find themselves in that “a gray area,” where making a definite diagnosis is not possible without an additional test.
What to expect during a PCA3 test?
Prostate cancer PCA samples are taking following a two-step procedure. During the first step, your urologist will need to perform a digital rectal exam or a prostate massage.
This procedure is performed by inserting one or two lubricated and gloved fingers in the rectum and pushing forward to meet and feel the prostate gland. In the process, your prostate will release a sample of cells into the prostatic urethra.
During the second step, you will need to provide a urine sample. It is essential to take the first stream of urine instead of the midstream doctors will recommend in other tests.
This initial stream drags along the prostatic cells in your prostatic urethra, and the sample is taken to the lab for PCR analysis. 20 to 30 mL of the first catch urine is what the laboratory will need for testing.
What happens after the test?
Depending on your results, your urologist will provide further guidance about your condition and start treatment or suggest your options.
PCA3 testing is accurate, and having a negative sample that is not close to 24 is likely to correlate with a negative biopsy as well. However, if your results are near the cut-off, your doctor might require another urinary PCA3 sample or any other test to evaluate your condition further.
Conclusion
In cases of positive PCA3 results that are not near the cut-off (over 35), your urologist may suggest an unnecessary biopsy of your prostate to analyze your case.
In some cases, you might be a candidate for active surveillance or radical prostatectomy, but each patient has an individual risk and should be evaluated separately.
