Prostate-specific antigen: any successor in sight?

Prostate cancer (PCa) is the most frequently diagnosed malignancy and the second leading cause of cancer death in men in the United States and other parts of the world. The lifetime risk of being diagnosed with PCa is approximately 16%. At present, the only widely accepted screening tools for PCa are prostate-specific antigen (PSA) and digital rectal examination. PSA is known to be prostate specific, but not PCa specific, and hence lacks the sensitivity to detect a large number of tumors, especially during the early stages. The PSA level is also known to be affected by many factors, such as medication, inflammation (benign prostatic hyperplasia and prostatitis), and urologic manipulation; hence, the controversy regarding the appropriate level of serum PSA that should trigger a biopsy or have clinical relevance to prostate metastases. Attempts to determine the level of prostate cells in peripheral blood by reverse transcriptase polymerase chain reaction did not significantly improve cancer diagnosis or predict postoperative failure. Therefore, the search continues for a novel biomarker or a panel of markers as well as other possible interventions to improve the use of PSA. This article reviews several possibilities.