While researchers still do not know the exact answer to this question, they have identified some risk factors. The most well established risk factors for prostate cancer are age, ethnicity, and family history.
What research is being done to validate and improve the PSA test?
The benefits of screening for prostate cancer are still being studied. The National Cancer Institute (NCI), a component of the National Institutes of Health, is currently conducting the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, or PLCO trial, to determine if certain screening tests reduce the number of deaths from these cancers. The DRE and PSA are being studied to determine whether yearly screening to detect prostate cancer will decrease a man's chance of dying from prostate cancer. Full results from this study are expected in several years.
Scientists also are researching ways to distinguish between cancerous and benign conditions, and between slow-growing cancers and fast-growing, potentially lethal cancers. Some of the methods being studied are:
PSA velocity: PSA velocity is the change in PSA levels over time. A sharp rise in the PSA level raises the suspicion of cancer and may indicate a fast growing cancer. A 2006 study found that men who had a PSA velocity above 0.35 ng/mL per year had a higher relative risk of dying from prostate cancer than men who had a PSA velocity less than 0.35 ng/mL per year (5). More studies are needed to determine if high PSA velocity more accurately detects prostate cancer early.
Age-adjusted PSA: Age is an important factor in increasing PSA levels. For this reason, some doctors use age-adjusted PSA levels to determine when diagnostic tests are needed. When age-adjusted PSA levels are used, a different PSA level is defined as normal for each 10-year age group. Doctors who use this method generally suggest that men younger than age 50 should have a PSA level below 2.4 ng/mL, while a PSA level up to 6.5 ng/mL would be considered normal for men in their 70s. Doctors do not agree about the accuracy and usefulness of age-adjusted PSA levels.
PSA density: PSA density considers the relationship of the PSA level to the size of the prostate. In other words, an elevated PSA might not arouse suspicion if a man has a very enlarged prostate. The use of PSA density to interpret PSA results is controversial because cancer might be overlooked in a man with an enlarged prostate.
Free versus attached PSA: PSA circulates in the blood in two forms: free or attached to a protein molecule. The free PSA test is more often used for men who have higher PSA values. Free PSA may help tell what kind of prostate problem a man has. With benign prostate conditions (such as BPH), there is more free PSA, while cancer produces more of the attached form. If a man's attached PSA is high but his free PSA is not, the presence of cancer is more likely. In this case, more testing, such as prostate biopsy, may be done. Researchers are exploring different ways to measure PSA and to compare these measurements to determine if cancer is present.
Alteration of PSA cutoff level: Some researchers have suggested lowering the cutoff levels that determine if a PSA measurement is normal or elevated. For example, a number of studies have used cutoff levels of 2.5 or 3.0 ng/mL (rather than 4.0 ng/mL). In such studies, PSA measurements above 2.5 or 3.0 ng/mL are considered elevated. Researchers hope that using these lower cutoff levels will increase the chance of detecting prostate cancer; however, this method may also increase overdiagnosis and false positive test results and lead to unnecessary medical procedures.
Protein patterns: Scientists are also studying a test that can rapidly analyze the patterns of various proteins in the blood. Researchers hope that this technique can determine if a biopsy is necessary when a person has a slightly elevated PSA level or an abnormal DRE.
New Test May Catch Prostate Cancer Earlier Than Ever Before: Leading PhD and Expert in Molecular Biology and Genetics Weighs in on Recent Study
A recent study at Johns Hopkins University has uncovered a new, accurate test for prostate cancer diagnosis. Measuring levels of an early prostate specific antigen called EPCA-2 has been found to be a more effective way to detect prostate cancer than the current PSA test, which more often than not produces false-positive or false-negative results. The EPCA-2 test is not yet available, but with nearly 95% accuracy during clinical trials, it could replace the PSA test as the new gold standard for the assessment of potential prostate cancer patients.
"Prostate cancer is the most common cancer among men, so accurate testing procedures are crucial," explains Dr. Shashi Pawar, PhD, director of molecular biology and genetics at Acupath Laboratories in New York. "With a new test such as the EPCA-2 test, future patients will be spared the agony of undergoing multiple examinations and procedures only to find out they do not have the cancer. Also, many patients that would normally go undiagnosed after the PSA test will be treated early on in the disease, which will mean a much longer life expectancy for prostate cancer patients."
Under current testing procedures, both a digital rectal examination, or DRE, and measurements of the prostate specific antigen in the bloodstream, called a PSA test, are administered to determine if a patient has prostate cancer. A DRE involves an examination of the prostate to observe physical abnormalities. A PSA test is a blood test that detects the levels of PSA present in the blood. High levels of PSA indicate a problem, as a healthy prostate secretes very little PSA into the bloodstream.
Experts agree that there are problems with the current accepted tests. "While the PSA test, combined with a DRE, is currently the most efficient way to diagnose prostate cancer, the diagnosis is often inaccurate because high levels of PSA also signify an enlarged or inflamed prostate, and these conditions are not necessarily related to prostate cancer," says Dr. Pawar. Following high PSA counts, many patients are advised to undergo invasive procedures such as biopsies. However, roughly 80% of patients that have biopsies do not have prostate cancer, which shows the inaccuracies of current testing procedures.
In addition to false positive tests, false negatives results are also common with the PSA test. Slow-growing prostate cancers often produce PSA counts within the normal range, despite the fact that cancer is present. No further treatment is prescribed to such patients, although they may have undetected disease. "Many men who think they do not have prostate cancer do not have follow-up tests, when they very well could have the disease," Pawar adds.
Published in the April issue of the journal Urology, the clinical study at Johns Hopkins examined 385 men, including patients with PSA levels less than what would cause further testing under current testing procedures, men with high levels of PSA but with negative biopsy findings, and those with various levels of prostate cancer. By measuring levels of EPCA-2, the study found that the test detected 94% of prostate cancer overall, compared to the 85% detected through the PSA test.
The EPCA-2 test also correctly diagnosed what would be false-positive and false-negative findings through the PSA test. The EPCA-2 test was negative for 97% of patients who did not have prostate cancer because it is able to correctly diagnose patients with high levels of PSA but without prostate cancer. In addition, EPCA-2 levels differentiate between patients whose cancer has spread to other parts of the body and patients whose cancer is contained within the prostate. With this differentiation, the aggressiveness of the cancer and the best treatment plan can be properly determined.
Johns Hopkins University expects that the larger clinical trials planned for the EPCA-2 test will confirm its accuracy, and this test could be made available to the public in as little as 18 months. In the meantime, the use of other molecular markers for the detection of prostate cancer is being explored. For example, in addition to the PSA test, Acupath Laboratories currently tests urine samples for the presence of the PCA-3 gene, which indicates that prostate cancer is present." This is a non-invasive procedure, and it has proven to be another accurate prostate detection method," Pawar claims.
While new prostate cancer testing methods are being experimented with, Dr. Pawar suggests that men over the age of fifty continue with routine PSA and DRE screenings. "Although somewhat ineffective," Pawar concedes, "The PSA test is currently the best way to detect prostate cancer. As the disease is so common, older men should be tested regularly in order to best treat the cancer before it's too late."
