Most prostate cancers have very slow growth; autopsy studies show increasing occurrence of a microscopic malignant lesion in the prostate gland without any other clinical evidence of the disease among older men: 30% at >50 yr, >40% at >75 yr, and approaching 100% at >90 yr (63). Because any cancer treatment has significant morbidity associated with it, a controversy in the success of PSA in detecting early CaP has been raised. If the malignancy is of slow growth, could its early detection and aggressive treatment result in "unnecessary" inconvenience of the patients and economic cost? For this reason, a search is on to detect the most dangerous of the CaP—the fast-growing, life-threatening ones. The PSA velocity has been used unsuccessfully in this regard, and newer markers are being sought. One example is the application of polymerase chain reaction (PCR) and reverse transcriptase PCR (RT-PCR) to detect micrometastatic prostate cancer cells (64). Another approach is the use of neural network analysis of multiple markers, which showed better specificity (57%) with high sensitivity (90%) at PSA <4 ^g/L (65). Newer serum markers like the other members of the kallikrein family (e.g., hK2) (66), prostate-specific membrane antigen (67), insulin-like growth factor 1 (68), alone or in combination of currently available markers, have been tested. The results, however, are too early to suggest any major advantage. In summary, although PSA assays have made tremendous contribution toward detecting CaP early, thus reducing CaP deaths, newer advances are needed to improve CaP diagnosis.
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