Critical assessment of tools to predict clinically insignificant prostate cancer at radical prostatectomy in contemporary men

Abstract
BACKGROUND. Overtreatment of prostate cancer (PCa) is a concern, especially in patients who might qualify for the diagnosis of insignificant prostate cancer (IPCa). The ability to identify IPCa prior to definitive therapy was tested. METHODS. In a cohort of 1132 men a nomogram was developed to predict the probability of IPCa. Predictors consisted of prostate‐specific antigen (PSA), clinical stage, biopsy Gleason sum, core cancer length and percentage of positive biopsy cores (percent positive cores). IPCa was defined as organ‐confined PCa (OC) with tumor volume (TV) <0.5 cc and without Gleason 4 or 5 patterns. Finally, an external validation of the most accurate IPCa nomogram was performed in the same group. RESULTS. IPCa was pathologically confirmed in 65 (5.7%) men. The 200 bootstrap‐corrected predictive accuracy of the new nomogram was 90% versus 81% for the older nomogram. However, in cutoff‐based analyses of patients who were qualified by our and the older nomograms as high probability for IPCa, respectively 63% and 45% harbored aggressive PCa variants at radical prostatectomy (Gleason score 7‐10, ECE, SVI, and/or LNI). CONCLUSIONS. Despite a high accuracy, currently available models for prediction of IPCa are incorrect in 10% to 20% of predictions. The rate of misclassification is even further inflated when specific cutoffs are used. As a consequence, extreme caution is advised when statistical tools are used to assign the diagnosis of IPCa. Cancer 2008. © 2008 American Cancer Society.