Optimal predictors of prostate cancer on repeat prostate biopsy: A prospective study of 1,051 men

Purpose:We compare the ability of total prostate specific antigen (PSA), pe rcent free PSA, PSA density and transition zone PSA density to predict the outcome of repeat prostatic biopsy in men with serum total PSA 4 to 10 ng./ ml. who were diagnosed with benign prostatic hyperplasia after initial biop sy. Materials and Methods: In this prospective study 1,051 men with total PSA 4 to 10 ng./ml. underwent transrectal ultrasound guided sextant biopsy with 2 additional transition zone biopsies. In 254 subjects biopsy specimens wer e also obtained from suspicious areas identified during transrectal ultraso und and digital rectal examination. All subjects with biopsy specimens nega tive for prostate cancer underwent repeat biopsy 6 weeks after initial biop sy. The ability of total PSA, percent free PSA, PSA density and transition zone PSA density to improve the diagnostic power of PSA testing was assesse d with univariate and multivariate analyses as well as receiver operating c haracteristics (ROC) curves. Results: Initial biopsy was positive (prostate cancer) in 231 and negative (benign prostatic hyperplasia) in 820 of the 1,051 subjects. Prostate cance r was detected on repeat biopsy in 10% of subjects (83 of 820) with negativ e initial biopsy. Percent free PSA and transition zone PSA density were the most accurate predictors of prostate cancer in these subjects. At a cutoff of 30% percent free PSA would have detected 90% of cancers (sensitivity) a nd eliminated 50% of unnecessary repeat biopsies (specificity). Sensitivity and specificity of transition zone PSA density at a cutoff of 0.26 ng./ml. /cc was 78% and 52%, respectively. ROC curve analysis also showed that perc ent free PSA was a significantly better predictor of repeat biopsy results than total PSA, PSA density and transition zone PSA density. The area under the ROC curve was 74.5% for percent free PSA, 69.1% for transition zone PS A density, 61.8% for PSA density and 60.3% for total PSA. Conclusions: At least 10% of patients with negative initial prostatic biops y results will be diagnosed with prostate cancer on repeat biopsy. Percent free PSA and transition zone PSA density enhance the specificity of PSA tes ting compared to total PSA or PSA density when determining which patients s hould undergo repeat biopsy. Repeat biopsy should be performed in patients with percent free PSA less than 30% or transition zone PSA density 0.26 ng. /ml./cc or greater. In our study percent free PSA was the most accurate pre dictor of prostate cancer in repeat biopsy specimens.