Comparative analysis of prostate specific antigen and its indexes in the detection of prostate cancer

Purpose: Prostate specific antigen (PSA) density and age referenced PSA have been proposed in an attempt to improve the power of PSA in the detection of early prostate cancer. Reported results have been controversial and disappointing. Because the association of gland volume with PSA is stronger than that of age we developed a new index, volume referenced PSA, and compared it to PSA density and other indexes. Materials and Methods: Volume referenced PSA was developed from a control group of 408 men without clinical evidence of prostate cancer using a standardized Z score. A retrospective analysis was performed comparing PSA and all its indexes in 580 men who underwent prostate biopsy. In addition to overall analysis, PSA and its indexes were evaluated with receiver operating characteristic curves by age and volume subcategories. Results: Cancer was identified in 35% of the 580 men. The number of missed cancers using established thresholds significantly favored volume referenced PSA clinically and statistically compared to all other indexes but it was equivalent to PSA alone clinically. Age referenced PSA prevented more biopsies from being done than did volume referenced PSA (39% versus 31%) but resulted in the diagnosis of 48% fewer cancers. Receiver operating characteristic curve analysis demonstrated a significantly better performance for volume referenced PSA and PSA density compared to PSA alone and age referenced PSA. Conclusions: Volume based PSA indexes are superior to PSA and age referenced PSA statistically. However, clinically volume referenced PSA is comparable to PSA, and both are superior to age referenced PSA and PSA density in the detection of prostate cancer.