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PSA (prostate-specific antigen)

The prostate-specific antigen is the most important laboratory parameter in connection with prostate cancer diagnosis. The PSA is not a tumour-specific, but only a prostate-specific protein. Consequently, elevated PSA levels are not necessarily associated with prostate cancer, but may also be indicative of inflammatory processes within the prostatic parenchyma or of BPH. Manipulations of the prostate resulting from the placement of a permanent catheter, digital rectal examination, needle biopsy, TUR procedures or intense sexual activity may also lead to elevated PSA levels. False-negative PSA levels may be caused, for example, by taking 5-alpha reductase inhibitors.

The probability of prostate cancer increases with increasing PSA concentration in the blood. When interpreting the PSA level, however, the age dependency of the serum concentration must also be taken into account, which is why age-specific PSA reference ranges have been introduced.

Age-specific PSA reference ranges PSA (ng/ml)
40-49 0,0-2,5
50-59 0,0-3,5
60-69 0,0-4,5
70-79 0,0-6,5

Because of the high percentage of both false-negative and false-positive results, the reliability of the PSA test is subject to controversy. Prostate cancer can be detected in 22% of all patients with a PSA level of 2.6-4 ng/ml and normal DRE results. On the other hand, studies have demonstrated that the positive predictive value of a PSA level of 4-10 ng/ml only ranges between 12% and 32%, which means that a false-positive result is produced in about 75% of the cases. This leads to a significantly large number of prostate needle biopsies performed unnecessarily.
By contrast, prostate cancer was detected in every second needle biopsy at a PSA level above 10 ng/ml, which is why needle biopsy is recommended predominantly within this reference range. Despite the high PSA level, a tumour that is still limited to the prostate is detected in about 25% of these patients.

Besides the absolute PSA level, the PSA velocity and doubling time can be drawn on to assess the risk of the presence of prostate cancer. A relatively high sensitivity (75%) and specificity (95%) for the presence of prostate cancer has been found at a borderline level of 0.75 ng/ml/year (PSA velocity).

PSA exists in free (fPSA) and bound form (in a complex with chymotrypsin and macroglobulin). The ratio of free PSA / bound PSA is another parameter used in the early detection of prostate cancer. If prostate cancer is present, the percentage of free PSA in the blood is lower than the percentage of PSA bound to proteases. In a prospective, randomised clinical trial, prostate cancer was detected by needle biopsy in 56% of the male patients with a ratio of <10% and in only 8% of those with a ratio of >10%.

Within the above-mentioned reference range of 4-10 ng/ml, unnecessary biopsies are reduced by 20% when taking this ratio into account. Within the reference range of 2.6-4 ng/ml, too, unnecessary biopsies can be reduced by 18% when taking into account the ratio of free PSA / bound PSA.
To what extent a population-wide PSA screening can reduce the PC-related mortality rate was investigated in two large randomised, prospective clinical trials: In the PLCO trial (Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial), 76,693 men in the U.S. were randomly assigned to undergo either a DRE or a PSA test or the currently applied standard on an annual basis.

After a follow-up period of 13 years, no significant difference in the PC-related mortality rate was revealed between the two groups. By contrast, the European ERSPC study (European Randomized Study of Screening for Prostate Cancer), in which 182,160 men aged between 50 and 74 years were randomised (PSA test every 5 years vs. no routine PSA test), revealed a significant reduction in the risk of dying of PC (risk reduced by 21%). To prevent one PC-related death, a total of 1,055 men had to be invited to screening and 37 men had to be treated for prostate cancer. There are 340 cases of overtreatment for seven cases of prevented PC-related deaths, which is equivalent to 48 cases of overtreatment for one case of prevented death.

Because of the partly conflicting results regarding population-wide PSA screening, the U.S. Preventive Task Force spoke out against PSA screening in 2012.

© Department of Urology Tuebingen - supported by "Förderverein Urologie e. V." - Nonprofit association