Prostate-specific antigen density as a proxy for predicting prostate cancer severity: Is there any difference between systematic and targeted biopsy?

Background: Prostate cancer screening with prostate-specific antigen (PSA) can result in unnecessary biopsies and overdiagnosis. Alternately, PSA density (PSAD) calculation may help support biopsy decisions; however, evidence of its usefulness is not concrete. Objective: To evaluate the predictive value of PSAD for clinically significant prostate cancer detection by systematic and MRI-targeted biopsies. Methods: This prospective study was conducted at two tertiary hospitals in Riyadh, Saudi Arabia, between December 2018 and November 2021. Patients suspected of prostate cancer were subjected to multi-parametric MRI, and for those with positive findings, systematic and targeted biopsies were performed. Clinically non-significant and significant prostate cancer cases were classified based on histopathology-defined ISUP grade or Gleason score. The PSAD was measured using the prostate volume determined by the MRI and categorized into <= 0.15, 0.16-0.20, and >0.20 ng/ml(2) subgroups. Results: Systematic and targeted biopsies were carried out for 284 patients. The discriminant ability of PSAD is higher in MRI-targeted biopsy compared with systematic biopsy (AUC: 0.77 vs. 0.73). The highest sensitivity (97%) and specificity (87%) were detected at 0.07 ng/ml(2) in targeted biopsy. More than half of the clinically significant cases were detected in the >0.2 ng/ml(2) PSAD category (systematic: 52.4%; targeted: 51.1%). The CHAID methodology found that the probability of having clinically significant cancer (CSC) in patients with PSAD >0.15 ng/ml(2) was more than threefold than that in patients with PSAD <= 0.15 ng/ml(2) (64% vs. 20.2%). When considered by age, in PSAD <= 0.15 ng/ml(2) subgroup, the percentage of CSC detection rate increased from 20.2% to 24.6% in patients aged >= 60 years.Conclusion: PSAD has good discriminant power for predicting clinically significant prostate cancer. A cutoff of 0.07 ng/ml(2) should be adopted, but should be interpreted with caution and by considering other parameters such as age.