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Background To investigate the role of Prostate Specific Antigen density (PSAD) in selecting prostate cancer patients for active surveillance (AS) and to determine a cutoff PSAD in identifying adverse pathological outcomes. Methods Data from 287 patients who underwent radical prostatectomy for prostate cancer were retrospectively reviewed. Six different AS protocols, the University of Toronto; Royal Marsden; John Hopkins; University of California San Francisco (UCSF); Memorial Sloan Kettering Cancer Center (MSKCC) and Prostate Cancer Research International: Active Surveillance (PRIAS), were applied to the cohort. Pre-operative demographics and pathological outcomes were analysed. Statistical analyses on the predictive factors of adverse pathological outcomes and significance of PSAD were performed. A cutoff PSAD with best balance between sensitivity and specificity in identifying adverse pathological outcome was determined. Results PSAD predicted adverse pathological outcomes better than Prostate Specific Antigen (PSA) level alone. The PSAD was significantly lower (0.12–0.13 ng/dl/ml) in protocols including PSAD (the John Hopkins and PRIAS) compared with the other four protocols not including PSAD as a selection criteria (0.21–0.25 ng/dl/dl, P = 0.00). PSAD predicted adverse pathological outcomes in all protocols not incorporating PSAD as an inclusion criteria ( P = 0.00–0.02). By the receiver operator characteristics curve analysis, it was found that a PSAD level of 0.19 ng/ml/ml had the best balance between sensitivity and specificity in predicting pathological adverse disease (Area under curve = 0.63, P = 0.004). Conclusion PSAD is necessary in selecting prostate cancer patients for active surveillance. It predicts adverse pathological outcomes in patients eligible for active surveillance better than PSA level alone. A PSAD cutoff at 0.19 ng/ml/ml has the best balance between sensitivity and specificity in predicting pathological adverse disease. We recommend using AS protocol incorporating PSAD as a selection criteria (in particular the PRIAS protocol with a cutoff PSAD at 0.2 ng/ml/ml) when recruiting prostate cancer patients for AS.

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