Prostate specific antigen (PSA) was introduced as a prostate cancer screening 
tool more than 20 years ago. However, there is continuing debate regarding its 
utility in screening for prostate cancer. Mass screening is costly, may result 
in the diagnosis and treatment of prostate cancers that never become clinically 
significant, and the evidence of a subsequent reduction in mortality is 
inconclusive. In addition to its role in screening, PSA is also used to monitor 
the progression of the disease, both localized and metastatic. Although the 
evidence is contradictory, PSA is still an important tool for monitoring patient 
progression following treatment of definitive localized prostate cancer. 
However, its use in monitoring castrate-resistant prostate cancer (CRPC) is more 
controversial, particularly in the context of novel targeted treatments, which 
may have little impact on PSA levels. These issues highlight the urgent need to 
identify prostate cancer biomarkers that will improve early disease detection, 
increase accuracy of diagnosis, determine the aggressiveness of disease, and 
monitor treatment efficacy, particularly in late-stage disease. This review 
discusses the key issues associated with the use of PSA as an early screening 
tool for prostate cancer, as a prognostic marker to measure disease progression 
in both early- and late-stage prostate cancer, and as a surrogate endpoint in 
clinical trials with new agents.