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Anterior zone (AZ) disease is present in one-fifth of men with newly diagnosed prostate cancer and has been associated with poor pathologic features. However, anterior targeted biopsies are not a routine part of active surveillance (AS) protocols. Our purpose is to assess the utility of AZ sampling for prostate biopsy in patients undergoing surveillance for low-risk prostate cancer.A prospective data collection of men enrolled in AS between 2006 and 2014 was performed. Patient and disease characteristics were collected, including number of positive cores and Gleason score on all diagnostic and surveillance biopsies. Progression was defined as incident Gleason > 6 in any core and/or receipt of definitive therapy including radical prostatectomy or radiotherapy. Rate of anterior disease and relationship to subsequent disease progression was assessed.A total of 85 men were included, of which 45% demonstrated progression. Median follow-up was 40 months. Among those undergoing AZ sampling at initial diagnosis, 37% presented with AZ disease. A total of 47% of men with AZ-only disease progressed, whereas 78% of men with AZ and peripheral zone disease progressed. This compares with a 39% rate of progression among men with only peripheral zone disease. Multivariable logistic regression identified increasing body mass index as a significant predictor of disease progression (odds ratio, 5.18; 95% confidence interval, 1.06-25.31; P = .04).Over one-third of men enrolled in AS for low-risk prostate cancer had AZ disease on diagnostic biopsy. Progression occurred in the majority of these men. AZ sampling should be considered in biopsy surveillance strategies.Anterior zone biopsy is not well-defined in prostate cancer. We assess the role of routine anterior-targeted biopsies in a cohort of patients undergoing active surveillance for low-risk prostate cancer. We identify high rates of cancer detection from the anterior zone as well as high rates of progression among patients with anterior tumors, indicating a potential benefit for routine anterior zone sampling in biopsy surveillance strategies.