Multifocal High Grade Prostatic Intraepithelial Neoplasia is a Risk Factor for Subsequent Prostate Cancer

Purpose: The risk of under diagnosed or development of subsequent prostate cancer and the treatment of patients diagnosed with high grade prostatic intraepithelial neoplasia remain controversial. We evaluated the relationship between high grade prostatic intraepithelial neoplasia on initial biopsy and the future presence of prostate cancer. Materials and Methods: From December 1997 to February 2008 a total of 328 men underwent a second prostate biopsy after being initially diagnosed with high grade prostatic intraepithelial neoplasia. Men with prostate cancer or atypia on initial biopsy were excluded from study. Another 335 men without high grade prostatic intraepithelial neoplasia, prostate cancer or atypia underwent a second prostate biopsy based on clinical suspicion alone. A Cox proportional hazards model was used to estimate the effect of high grade prostatic intraepithelial neoplasia on the subsequent diagnosis of prostate cancer after adjustment for prostate specific antigen, age, presence of inflammation, abnormal digital rectal examination and number of cores obtained at biopsy. High grade prostatic intraepithelial neoplasia was also stratified into multifocal disease and laterality. Adjusted Kaplan-Meier plots were generated to estimate the rates of prostate cancer. Results: High grade prostatic intraepithelial neoplasia alone on initial prostate biopsy had a significant effect on the subsequent diagnosis of prostate cancer (HR 1.89; 95% CI 1.39, 2.55; p < 0.0001). Stratifying high grade prostatic intraepithelial neoplasia into multifocal and bilateral disease significantly increased the hazard ratios to 2.56 (95% CI 1.83, 3.60) and 2.20 (95% CI 1.51, 3.21), respectively, resulting in estimated 3-year cancer rates of 29.0% and 37.0% compared to 12.5% and 18.9%, respectively, following benign biopsy. Conclusions: Multifocal and bilateral disease are adverse features of high grade prostatic intraepithelial neoplasia that significantly increase the risk of prostate cancer despite adjusting for other clinical indicators such as prostate specific antigen and abnormal digital rectal examination.