Study highlights insensitivity of PSA screeningBMJ 2005; 331 doi: https://doi.org/10.1136/bmj.331.7508.67-a (Published 07 July 2005) Cite this as: BMJ 2005;331:67
Many prostate cancers, including high grade tumours, can be missed when the prostate specific antigen (PSA) test is used in screening, even when the concentration of PSA at which further investigations are carried out is set low.
New research shows that there is no specific cut-off concentration for PSA below which the risk of prostate cancer is zero. The large follow-up study has showed a continuum of risk at all concentrations of PSA (JAMA 2005;294: 66-70). It confirmed previous concerns about the value of PSA testing, with no studies showing that it reduced prostate cancer mortality.
The study analysed data from 8575 men in the placebo group of the prostate cancer prevention trial, a study of nearly 19 000 healthy US and Canadian men aged 55 years or older who don't have prostate cancer and with PSA concentrations ≤3 ng/ml and whose results of digital rectal examination were normal.
The men were followed up for seven years and had annual measurement of PSA and digital rectal examination. A prostate biopsy was recommended if their PSA concentration exceeded 4 ng/ml or results of rectal examination were abnormal.
Nearly two thirds of them (5587 or 65%) had at least one biopsy. Of these, just over a fifth (1225) received a diagnosis of prostate cancer (14% of the whole placebo group).
In the 1213 cases of cancer in which the Gleason grade was recorded, 250 (21%) were recorded as Gleason grade 7 or higher and 57 (5%) were Gleason grade 8 or higher.
Results showed that with the commonly used cut-off value for PSA of 4.1 ng/ml (above which a prostate biopsy is generally done) only 21% of cancer cases would have been detected (the sensitivity) and that the false positive rate (specificity) was 6.2%.
Lowering the cut-off value to 1.1 ng/ml would have detected 83.4% of cancer cases but would have resulted in 61% of men without cancer having a biopsy. Overall the results showed that there was no single cut-off concentration that would simultaneously yield both high sensitivity and high specificity.
PSA thresholds of 2.1 and 3.1 ng/ml yielded sensitivities of 53% and 32%, respectively, and specificities of 73% and 87%.
The lead researcher, Ian Thompson, who is the Henry B and Edna Smith Dielman Memorial Professor in Urologic Science at the University of Texas Health Science Center at San Antonio, said: “There is no cutpoint of PSA with simultaneous high sensitivity and high specificity for monitoring healthy men for prostate cancer, but rather a continuum of prostate cancer risk at all values of PSA.
“The implications of this analysis are substantial. Prior to clinical use of biomarkers or other tests for cancer screening, properly designed validation studies are essential.”
The fact that many prostate cancers, including high grade tumours, are missed at low PSA concentrations could explain the discrepancy between the high rate of PSA screening over the past 15 years and the lack of reduction in prostate cancer mortality in the United States, Professor Thompson said.
He concluded: “Patients and healthcare professionals must be re-educated that there is a continuum of risk and no clearly defined PSA cutpoint at which to recommend biopsy. It will be the patient, in concert with his healthcare professional, who will ultimately have to weigh the sensitivity-specificity trade-offs in combination with the uncertain natural history of the disease to determine whether further evaluation with a prostate biopsy is appropriate.”
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