Clinical Utility of Prostate Health Index for Diagnosis of Prostate Cancer in Patients with PI-RADS 3 Lesions

SIMPLE SUMMARY: Multi-parametric magnetic resonance imaging (mpMRI) is regarded as an essential tool for identifying prostate cancer (PCa) in suspected cases. However, unnecessary biopsies continue to be performed in real clinics, especially for prostate imaging reporting and data system version 2 (PI-RADS v2) score-3 lesions, corresponding to the “gray zone”. To aid the diagnosis of PCa, as well as of clinically significant PCa (csPCa), in patients with PI-RADSv2 score-3 lesions, we evaluated the clinical utility of the prostate health index (PHI). When a biopsy was restricted to those patients with PI-RADSv2 score-3 lesions and a PHI of ≥30, 34.4% of unnecessary biopsies could be avoided at the cost of missing 8.3% of overall PCa cases. However, there were no cases of missed csPCa diagnosis. The combination of PHI and PI-RADSv2 score-3 lesions offered higher accuracy in the diagnosis of PCa as well as of csPCa. ABSTRACT: The risk of prostate cancer (PCa) in prostate imaging reporting and data system version 2 (PI-RADSv2) score-3 lesions is equivocal; it is regarded as an intermediate status of presented PCa. In this study, we evaluated the clinical utility of the prostate health index (PHI) for the diagnosis of PCa and clinically significant PCa (csPCa) in patients with PI-RADSv2 score-3 lesions. The study cohort included patients who underwent a transrectal ultrasound (TRUS)-guided, cognitive-targeted biopsy for PI-RADSv2 score-3 lesions between November 2018 and April 2021. Before prostate biopsy, the prostate-specific antigen (PSA) derivatives, such as total PSA (tPSA), [-2] proPSA (p2PSA) and free PSA (fPSA) were determined. The calculation equation of PHI is as follows: [(p2PSA/fPSA) × tPSA ½]. Using a receiver operating characteristic (ROC) curve analysis, the values of PSA derivatives measured by the area under the ROC curve (AUC) were compared. For this study, csPCa was defined as Gleason grade 2 or higher. Of the 392 patients with PI-RADSv2 score-3 lesions, PCa was confirmed in 121 (30.9%) patients, including 59 (15.1%) confirmed to have csPCa. Of all the PSA derivatives, PHI and PSA density (PSAD) showed better performance in predicting overall PCa and csPCa, compared with PSA (all p < 0.05). The AUC of the PHI for predicting overall PCa and csPCa were 0.807 (95% confidence interval (CI): 0.710–0.906, p = 0.001) and 0.819 (95% CI: 0.723–0.922, p < 0.001), respectively. By the threshold of 30, PHI was 91.7% sensitive and 46.1% specific for overall PCa, and was 100% sensitive for csPCa. Using 30 as a threshold for PHI, 34.4% of unnecessary biopsies could have been avoided, at the cost of 8.3% of overall PCa, but would include all csPCa.