The use of PSA for the detection of prostate cancer leads to an earlier diagnosis and probably more curable stages of the disease are detected. On the other hand, knowledge of the natural history of early lesions suggests that indiscriminate use of PSA will lead to overdiagnosis and overtreatment in some cases (6). Information on the effectiveness of treatment is currently unavailable, and no evidence exists that early diagnosis and treatment will lead to an improvement of disease-related and overall mortality (7,8). Despite these uncertainties it is proposed that use of the PSA test should not be withheld from symptomatic men and those who wish to be examined for the presence of prostate cancer. Application to the general population should depend, however, on the results of prospective randomized studies showing that early detection and treatment can decrease prostate cancer mortality (9). Since the positive predictive value (number of positive tests in patients with the disease divided by the total number of tests performed) of PSA in screening populations is disturbingly low (~30%) it is necessary to enhance the specificity of the tumour marker (10-13).
Increasing the specificity for prostate cancer detection and population based screening
Possible ways to increase the specificity of t-PSA in the diagnosis of prostate cancer may include determination of t-PSA/prostate volume-ratio (14-16), use of age-specific reference ranges (17-19) or measurement of serial t-PSA increase over time (PSA "velocity" or "doubling time") (20-22) but evidence is as yet inconclusive or the application is of limited use in daily practice. The use of age-specific reference ranges cannot be recommended yet, since no trials are available showing the efficacy of prostate biopsies for age-specific PSA decision points of concentrations lower than 4 ng/ml. For highly selected sub-populations, the free to total PSA ratio may hold most promise to enhance the specificity of PSA for detecting prostate cancer (1-3, 23-27) but considerable further research is required.
Despite well documented drawbacks, t-PSA determinations can be recommended in symptomatic men, if the diagnosis of prostate cancer alters the treatment decision. In the absence of studies documenting that early detection of prostate cancer does more good than harm it may be reasonable to restrict PSA testing in asymptomatic individuals to those who agree to undergo prostate biopsy in case of elevated t-PSA levels and have a life expectancy of more than ten years (28, 29). At this time, there is no evidence to encourage the widespread use of PSA testing or the introduction of population based screening to detect prostate cancer (7).