Prostate Health Index Density Outperforms Prostate-specific Antigen Density in the Diagnosis of Clinically Significant Prostate Cancer in Equivocal Magnetic Resonance Imaging of the Prostate: A Multicenter Evaluation

Abstract

<p>Purpose:<br>We compare Prostate Health Index, Prostate Health Index density, and PSA density in predicting clinically significant prostate cancer in MRI-guided prostate biopsy.</p><p>Materials and Methods:<br>This is a multicenter evaluation of prospectively maintained prostate biopsy databases at 10 urology centers. Men with Prostate Health Index and MRI-guided targeted and systematic prostate biopsy performed and without prior prostate cancer diagnosis were included. The additional value of PSA density, Prostate Health Index, and Prostate Health Index density to MRI PI-RADS (Prostate Imaging Reporting & Data System) score was evaluated with multivariable analyses, area under the curve, and decision curve analyses. The proportion of unnecessary biopsies that can be avoided are estimated for clinically significant prostate cancer (International Society of Urological Pathology group ≥2 prostate cancer).</p><p>Results:<br>A total of 1,215 men were analyzed. Prostate cancer and clinically significant prostate cancer were diagnosed in 51% (617/1,215) and 35% (422/1,215) of men, respectively. Clinically significant prostate cancer was diagnosed in 4.4% (3/68), 15% (72/470), 39% (176/446), and 74% (171/231) of highest PI-RADS score of 2, 3, 4, and 5 lesions, respectively. In multivariable analyses, independent predictors for clinically significant prostate cancer detection included Prostate Health Index (OR 1.04), prostate volume (OR 0.97), and PI-RADS score 4 (OR 2.81) and 5 (OR 8.34). Area under the curve for clinically significant prostate cancer of PI-RADS + Prostate Health Index density (0.85) was superior to PI-RADS + PSA density (0.81), Prostate Health Index density (0.81), Prostate Health Index (0.78), PI-RADS (0.76), PSA density (0.72), and PSA (0.60) in the whole cohort, and the superiority of Prostate Health Index density was also observed in PI-RADS 3 lesions. Decision curve analysis showed Prostate Health Index density achieving the best net clinical benefit in PI-RADS 3 or 4 cases. Among PI-RADS 3 lesions, using cutoffs of PSA density 0.15, Prostate Health Index 38.0, and Prostate Health Index density 0.83 could reduce 58%, 67%, and 72% of unnecessary biopsies, respectively.</p><p>Conclusions:<br>Prostate Health Index density outperformed Prostate Health Index or PSA density in clinically significant prostate cancer detection in men with multiparametric MRI performed, and further reduced unnecessary biopsies in PI-RADS 3 lesions.</p><p>Prostate cancer (PCa) is the second most diagnosed cancer in men worldwide, and it is estimated the incidence in Asia will double in 20 years. While PSA is one of the most widely used serum markers for PCa screening, its diagnostic value remains controversial due to its drawbacks of false positivity, which may lead to unnecessary prostate biopsies, and overdiagnosis and overtreatment of indolent PCas.</p><p>According to European Association of Urology (EAU) guidelines, prostate biopsies are offered for patients with a suspicious lesion on multiparametric magnetic resonance imaging (mpMRI; ie, Prostate Imaging Reporting & Data System [PI-RADS] ≥3), and usually omitted for patients with PI-RADS ≤2. Yet, among these patients with PI-RADS ≤2, 11% of the clinically significant prostate cancer (csPCa) would be missed if no biopsy were done according to the PROMIS trial.</p><p>To further reduce unnecessary biopsies and improve the detection of csPCa in cases with equivocal MRI prostate finding of PI-RADS 3, PSA density (PSAD) has been used in combination with MRI PI-RADS score in determining the risk of csPCa, and various cutoffs have been suggested to reduce unnecessary biopsies.</p><p>Prostate Health Index (PHI) is a formula including total PSA, free PSA (fPSA), and a PSA isoform called p2PSA, and it has been shown in multiple studies to outperform PSAD and fPSA in csPCa prediction. Prostate Health Index density (PHID; PHI divided by prostate volume) has also been introduced in recent years to outperform PHI alone in PCa diagnosis.</p><p>Evidence on the value of PHI or PHID in patients with MRI performed is limited. This multicenter study was conducted to investigate the additional value of PHI and PHID in predicting csPCa in Asian men with MRI prostate performed, with a particular focus on equivocal MRI scans.</p>