Studies Find PSA Screening Unreliable
FRIDAY Sept. 25, 2009 -- The inability of the prostate specific antigen (PSA) test to distinguish between deadly and harmless prostate cancers makes it unusable as a population-wide screening tool, new research claims.
Because of its unreliability, results from the test lead to overdiagnosis and overtreatment, according to two reports in the Sept. 25 online edition of BMJ.
"Our findings strongly indicate that, in addition to PSA, further biomarkers are needed before inferring population-based screening for prostate cancer," said Benny Holmstrom, a urologist with Gavle Hospital in Gavle, Sweden, and lead author of the first study.
Holmstrom's group studied the PSA tests of 540 men diagnosed with prostate cancer. Their PSA was measured several years before being diagnosed. They compared those tests with PSA tests from 1,034 men without prostate cancer.
"Our main finding was that no cut-off level for PSA attained the criteria formally required for a screening test," Holmstrom said. "Furthermore, we found that in men with a prediagnostic PSA level below 1 nanogram per milliliter, only six men [1.2 percent] were later diagnosed with a high-risk prostate cancer. Hence, PSA levels below [that] almost ruled out a future high-risk prostate cancer diagnosis."
"The direct implication of our findings in a screening situation is that no matter which PSA cut-off you adopt for selecting men for further diagnostic work-up, you will either have too many false positives or too many false negatives," said study co-author Mattias Johansson, a postdoctoral fellow at Umea University in Sweden.
"Given the current trend in lowering the PSA cut-off to about 3 nanograms per milliliter, it seems clear that a large number of healthy men will be subject to painful, stressful and costly diagnostic procedures," he said. "In addition, and perhaps more serious, is the wide overdiagnosis of slow-growing tumors causing unnecessary medical treatment and anxiety."
Holmstrom advised men to discuss with their doctor whether or not they should have a PSA test.
In a second report, Jennifer Stark, a research fellow at Harvard School of Public Health in Boston, agreed that "before PSA testing is performed, men should be thoroughly informed about the PSA test itself and the fact that the test cannot tell whether they have a life-threatening cancer."
In that analysis, Stark and her colleagues found the data on costs and benefits remain insufficient to support population-based PSA screening for prostate cancer.
"PSA levels increase not only during cancer development, but also in some benign conditions, and PSA cannot differentiate between indolent and lethal prostate cancer," Stark said.
"We know these limitations lead to false-positive results, overdiagnosis and overtreatment, but the psychological and financial costs of PSA testing for the early detection of prostate cancer have not yet been measured precisely enough to determine if they outweigh a modest benefit in survival associated with screening," she said.
Although most agencies providing recommendations on prostate cancer screening, especially those outside the United States, do not recommend routine PSA testing for the early detection of prostate cancer, it continues to be performed frequently, Stark noted.
"While it is not completely clear whether the tests are more often initiated by patient or provider, data suggest that men are often not informed about the limitations of the test and about the need to interpret the results of a positive or negative test result with those limitations in mind," she said.
Dr. Dragan Ilic, a senior lecturer at Monash Institute of Health Services Research at Monash University in Australia, and author of an accompanying journal editorial, said the data about the value of PSA tests remains confusing.
"Evidence from two recently published randomized, controlled trials provide conflicting recommendations on the merits of using the PSA test in screening men for prostate cancer," he added.
Doctors and patients are faced with conflicting evidence about the merits of screening and how to use the PSA test as a screening tool, Ilic said.
"In the absence of conclusive evidence to inform PSA testing, clinicians should initiate an informed discussion with patients, with the aid of appropriate patient education materials, to ensure that patients understand the uncertainty surrounding screening for prostate cancer and so can make an informed, shared decision," he said.
PSA is a protein made by the prostate gland. It is found in small amounts in the blood of healthy men, and is often elevated in men with prostate cancer, but also in men with benign prostate enlargement.
Posted: September 2009