Serum markers for early detection and staging of prostate cancer. Status report on current and future markers

Abstract

Prostate-specific antigen (PSA) is by far the most important tumor marker in urology and has revolutionized early detection, staging, treatment, and aftercare of prostate cancer [77]. Despite these merits, inadequacies have surfaced which prohibit characterizing PSA as a perfect tumor marker. First, PSA is not a marker for prostate cancer as such:benign prostate hyperplasia, prostatitis [40,69], or prostatic manipulation [66] influence serum concentrations of PSA and lead to biopsies that are costly and potentially harmful. In the entire PSA range between 4 and 10 ng/ml, the specificity at a sensitivity of 95% continues to remain unsatisfactory. Furthermore, 30-40% of all men develop prostate cancer, but only 9-11% a clinically significant tumor burden, and 2.5-4.3% of all men die from prostate cancer. The vast majority of all carcinomas are thus in significant in terms of the patient's life expectancy. PSA is incapable of differentiating these clinically insignificant carcinomas from significant ones. Finally, prevalence of prostate cancer is increasing due to higher life expectancy. On the other hand, particularly patients aged 50-70 years are the ones who develop an aggressive form of carcinoma and profit from early detection and treatment. The global term "total PSA"encompasses a heterogeneous blend of bound and free molecular forms of PSA. Complexed PSA represents the major form of total PSA. The smaller portion, free PSA, is enzymatically inactive. In addition, different isoforms of free PSA exist Recent studies provide support for clinical application of these isoforms for early detection of prostate cancer. Clinical measurement of human glandular kallikrein 2 (hK2) serves as a complementary marker to PSA for early detection of prostate cancer and constitutes a considerable improvement over PSA as a staging marker for clinically localized prostate cancer. This overview summarizes established and potentially new forms of PSA and hK2 for early detection and staging of prostate cancer.