Review of diagnostic markers for prostate cancer

This review concentrates mainly on currently available markers for prostate cancer and cannot cover the multiple marker substances which are now in experimental and clinical development. Prostate-specific antigen (PSA) is still the main diagnostic tool despite its serious limitations, which will be addressed. Studies of new diagnostic markers and also most studies of PSA are subject to attribution or assignment bias, which limits the accuracy of the resulting information. Usually a more or less arbitrarily chosen cut-off value is used as a "gold standard" to determine the indication for the decisive test, a prostatic biopsy, and the assumption is made that no cancers are present below that cut-off value. This assumption has been proved wrong by findings in the control arm of the Prostate Cancer Prevention Trial (PCPT), where more than 5,000 men were biopsied independent of their PSA status. As an example: a PSA cut-off value of4.0 ng/ml, a commonly used biopsy indicator, missed about 75% of all biopsy-detectable cancers. On the other hand, sextant biopsies in all men led to a detection rate of 21.9%, evidence of the diagnosis of many cases in men who otherwise would never have had any clinical signs of prostate cancer (overdiagnosis). The only way out of this dilemma is a better understanding of the natural history of those cases with low PSA values that would not be considered suspicious with the use of currently available risk indicator nomograms. The European Randomised Study of Screening for Prostate Cancer (ERSPC) offers such an opportunity. Results are summarised in this chapter. Evidence is provided that men diagnosed in the low PSA ranges (< 3.0 ng/ml) usually present with more favourable cancers which, when identified, are often eligible for active surveillance after application of the appropriate nomogram. In addition, the data in the setting of the ERSPC study show that biopsy in such men can safely be delayed until PSA rises to above a cut-off value of 3.0 ng/ml. The limitations of PSA discussed herein clearly point to the need to find better diagnostic and prognostic markers for prostate cancer.