The deficiencies of serum PSA as a prostate-cancer-specific diagnostic test are 
well recognized. Thus, the development of novel biomarkers for prostate cancer 
detection remains an important and exciting challenge. Noninvasive urine-based 
tests are particularly attractive candidates for large-scale screening 
protocols, and biomarker discovery programs using urine samples have emerged for 
detecting and predicting aggressiveness of prostate cancer. Some new biomarkers 
already outperform serum PSA in the diagnosis of this disease. Currently, the 
PCA3 (prostate cancer antigen 3) urine test is probably the best adjunct to 
serum PSA for predicting biopsy outcome, and has proven its clinical relevance 
by surpassing the predictive abilities of traditional serum biomarkers. New 
research methods are also emerging, and high-throughput technologies will 
facilitate high-dimensional biomarker discovery. Future approaches will probably 
integrate proteomic, transcriptomic and multiplex approaches to detect novel 
biomarkers, and aim to identify combinations of multiple biomarkers to optimize 
the detection of prostate cancer. In addition, an unmet need remains for markers 
that differentiate indolent from aggressive cancers, to better inform treatment 
decisions.