Prostate-specific antigen and diagnosing early malignancies of the prostate

Prostate-specific antigen is a kallikrein-like serine protease that is produced exclusively by the epithelial cells of all types of prostatic tissue, benign and malignant. Physiologically, it is present in the seminal fluid at high concentration and functions to cleave the high molecular weight protein responsible for the seminal coagulum into smaller polypeptides. This action results in liquefaction of the coagulum. Prostate-specific antigen is also present in the serum and can be measured reliably by several different assays. Although the protein is prostate-specific, it is not prostate-cancer-specific. As a result, benign conditions such as benign prostatic hyperplasia, prostatitis and infarction, as well as prostatic intraepithelial neoplasia, can be associated with elevated serum levels of prostate-specific antigen. Approximately 25% of men with benign prostatic hyperplasia have an elevated serum value of prostate-specific antigen, whereas 35% to 40% of patients with organ-confined prostate cancer have a level within the reference range. Prostate-specific antigen can identify some cancers not detectable by digital rectal examination; alternatively, this examination can identify cancers not detectable from the serum prostate-specific antigen concentration. Thus, the most complete evaluation of the prostate gland is achieved when both the prostate-specific antigen value and the digital rectal examination are used. The density and the rate of change of serum prostate-specific antigen are new concepts to improve the ability of prostate-specific antigen to detect early prostate cancer. Preliminary results are encouraging, but additional studies are required to determine the true usefulness of these new variables. Thus, in 1992, determination of the prostate-specific antigen value is a valuable new tool for the practicing physician and will be instrumental in our campaign to diagnose clinically significant prostate cancer at an early, curable stage.