Prostate cancer (CaP) remains the second most common cancer among men worldwide [1]. The greatest hope of reducing CaP mortality is therefore through early detection and prevention [2]. Prostate-specific antigen (PSA) testing is the mainstay of early detection of CaP [3] at the cost of overdiagnosis and overtreatment due to its limited sensitivity (of 20.5%) and specificity (ranging from 51 to 91%) [4,5], especially in the men with PSA between 4.0 and 20.0 ng/ml (low and medium clinical risk category) [6]. To improve specificity and thus avoid biopsies and reduce over diagnosis, several urine- and blood-based biomarkers have been proposed. These include STHLM3, prostate health index (PHI), 4K score and PCA3 [7]. Among these, PHI is one of the most robustly studied CaP biomarkers in the literature and also one of the lowest cost tests available [8]. The PHI involves measurement of p2PSA, percent free PSA and total PSA. Levels of these 3 proteins are then combined using the formula [9] PHI = (p2PSA/free PSA)  ×  PSA1/2, clinical studies have suggested that PHI outperforms PSA in CaP detection [10].

In the context of medical imaging, multiparametric magnetic resonance imaging (mpMRI) has emerged as an important tool in the diagnosis and local staging of CaP [11]. mpMRI allows not only assessing incidence risk of CaP, but also guiding biopsy site selection to increase the detection rate [12]. It has been suggested that the use of mpMRI-targeted biopsy made 20% more clinically significant prostate cancers (CsCaP) being identified and better at avoiding detection of insignificant disease compared to the transrectal ultrasonography (TRUS)-guided prostate biopsy [13]. Currently, the Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1) released in 2019 is commonly used as a standardized reporting system of mpMRI [14].

There is no question that using the combination of PHI and mpMRI is a promising strategy and numerous studies [15], [16], [17], [18] have confirmed this point. However, few studies have explored how PHI and MRI should be used in concert. Therefore, we conducted this study to explore diagnostic performance of them and evaluate different strategies combining PHI and mpMRI for the detection of CsCaP in an Asian population.