Diagnostic Performance of Prostate-specific Antigen Density for Detecting Clinically Significant Prostate Cancer in the Era of Magnetic Resonance Imaging: A Systematic Review and Meta-analysis

There has been a dramatic increase in the use of prostate magnetic resonance imaging (MRI) in the diagnostic workup. With prostate volume calculated from MRI, prostate-specific antigen density (PSAD) now is a ready-to-use parameter for prostate cancer (PCa) risk stratification before prostate biopsy, especially among patients with negative MRI or equivocal lesions. In this review, we aimed to evaluate the diagnostic performance of PSAD for clinically significant prostate cancer (CSPCa) among patients who received MRI before prostate biopsy. Two investigators performed a systematic review according of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) criteria. Studies (published between January 1, 2012, and December 31, 2021) reporting the diagnostic performance (outcomes) of PSAD (intervention) for CSPCa among men who received prebiopsy prostate MRI and subsequent prostate biopsy (patients), using biopsy pathology as the gold standard (comparison), were eligible for inclusion. A total of 1536 papers were identified in PubMed, Scopus, and Embase. Of these, 248 studies were reviewed in detail and 39 were qualified. The pooled sensitivity (SENS) and specificity (SPEC) for diagnosing CSPCa among patients with positive MRI were, respectively, 0.87 and 0.35 for PSAD of 0.1 ng/ml/ml, 0.74 and 0.61 for PSAD of 0.15 ng/ml/ml, and 0.51 and 0.81 for PSAD of 0.2 ng/ml/ml. The pooled SENS and SPEC for diagnosing CSPCa among patients with negative MRI were, respectively, 0.85 and 0.36 for PSAD of 0.1 ng/ml/ml, 0.60 and 0.66 for PSAD of 0.15 ng/ml/ml, and 0.33 and 0.84 for PSAD of 0.2 ng/ml/ml. The pooled SENS and SPEC among patients with Prostate Imaging Reporting and Data System (PI-RADS) 3 or Likert 3 lesions were, respectively, 0.87 and 0.39 for PSAD of 0.1 ng/ml/ml, 0.61 and 0.69 for PSAD of 0.15 ng/ml/ml, and 0.42 and 0.82 for PSAD of 0.2 ng/ml/ml. The post-test probability for CSPCa among patients with negative MRI was 6% if PSAD was <0.15 ng/ml/ml and dropped to 4% if PSAD was <0.10 ng/ml/ml. In this systematic review, we quantitatively evaluated the diagnosis performance of PSAD for CSPCa in combination with prostate MRI. It demonstrated a complementary performance and predictive value, especially among patients with negative MRI and PI-RADS 3 or Likert 3 lesions. Integration of PSAD into decision-making for prostate biopsy may facilitate improved risk-adjusted care. Prostate-specific antigen density is a ready-to-use parameter in the era of increased magnetic resonance imaging (MRI) use in clinically significant prostate cancer (CSPCa) diagnosis. Findings suggest that the chance of having CSPCa was very low (4% or 6% for those with negative prebiopsy MRI or Prostate Imaging Reporting and Data System (Likert) score 3 lesion, respectively, if the PSAD was <0.10 ng/ml/ml), which may lower the need for biopsy in these patients.