Re-examining Prostate-specific Antigen (PSA) Density: Defining the Optimal PSA Range and Patients for Using PSA Density to Predict Prostate Cancer Using Extended Template Biopsy

Objective: To compare the predictive accuracy of prostate-specific antigen (PSA) density vs PSA across different PSA ranges and by prior biopsy status in a prospective cohort undergoing prostate biopsy. Materials and Methods: Men from a prospective trial underwent an extended template biopsy to evaluate for prostate cancer at 26 sites throughout the United States. The area under the receiver operating curve assessed the predictive accuracy of PSA density vs PSA across 3 PSA ranges (<4 ng/mL, 4-10 ng/mL, >10 ng/mL). We also investigated the effect of varying the PSA density cutoffs on the detection of cancer and assessed the performance of PSA density vs PSA in men with or without a prior negative biopsy. Results: Among 1290 patients, 585 (45%) and 284 (22%) men had prostate cancer and significant prostate cancer, respectively. PSA density performed better than PSA in detecting any prostate cancer within a PSA of 4-10 ng/mL (area under the receiver operating characteristic curve [AUC]: 0.70 vs 0.53, P < .0001) and within a PSA >10 mg/mL (AUC: 0.84 vs 0.65, P < .0001). PSA density was significantly more predictive than PSA in detecting any prostate cancer in men without (AUC: 0.73 vs 0.67, P < .0001) and with (AUC: 0.69 vs 0.55, P < .0001) a previous biopsy; however, the incremental difference in AUC was higher among men with a previous negative biopsy. Similar inferences were seen for significant cancer across all analyses. Conclusion: As PSA increases, PSA density becomes a better marker for predicting prostate cancer compared with PSA alone. Additionally, PSA density performed better than PSA in men with a prior negative biopsy.