A Clinically Significant Prostate Cancer Predictive Model Using Digital Rectal Examination Prostate Volume Category to Stratify Initial Prostate Cancer Suspicion and Reduce Magnetic Resonance Imaging Demand

Early detection of PCa (PCa) has evolved towards clinically significant PCa (csPCa) after the spread of pre-biopsy multiparametric magnetic resonance imaging (mpMRI). However, PCa suspicion remains based on prostate-specific antigen (PSA) elevation and/or abnormal digital rectal examination (DRE). This change of paradigm and approach has reduced unnecessary prostate biopsies and overdetection of insignificant PCa, while the demand for mpMRI has skyrocketed despite its implementation not being allowed at all sites. The European Association of Urology (EAU) proposes risk-organized models for early detection of csPCa stratifying the initial PCa suspicion to reduce MRI scans and then prostate biopsies after mpMRI. Risk calculators are efficient tools for individualizing the risk of csPCa, especially when prostate volume is included in the predictive models. After the development and external validation of the Barcelona MRI risk calculator (BCN-RC 2) for the selection of candidates for prostate biopsy, we have now developed and externally validated BCN-RC 1 with the aim of reduce mpMRI demand. Both BCN-RC 1 and RC 2 are ready to be integrated in a risk-organized model for early detection of csPCa. A predictive model including age, PCa family history, biopsy status (initial vs repeat), DRE (normal vs abnormal), serum prostate-specific antigen (PSA), and DRE prostate volume ca-tegory was developed to stratify initial PCa suspicion in 1486 men with PSA > 3 ng/mL and/or abnormal DRE, in whom mpMRI followed; 2- to 4-core TRUS-guided biopsies where Prostate Imaging Report and Data System (PI-RADS) > 3 lesions and/or 12-core TRUS systematic biopsies were performed in one academic institution between 1 January 2016-31 December 2019. The csPCa detection rate, defined as International Society of Uro-Pathology grade group 2 or higher, was 36.9%. An external validation of designed BCN-RC 1 was carried out on 946 men from two other institutions in the same metropolitan area, using the same criteria of PCa suspicion and diagnostic approach, yielded a csPCa detection rate of 40.8%. The areas under the receiver operating characteristic curves of BCN-RC 1 were 0.823 (95% CI: 0.800-0.846) in the development cohort and 0.837 (95% CI: 0.811-0.863) in the validation cohort (p = 0.447). In both cohorts, BCN-RC 1 exhibited net benefit over performing mpMRI in all men from 8 and 12% risk thresholds, respectively. At 0.95 sensitivity of csPCa, the specificities of BCN-RC 1 were 0.24 (95% CI: 0.22-0.26) in the development cohort and 0.34 (95% CI: 0.31-0.37) in the validation cohort (p < 0.001). The percentages of avoided mpMRI scans were 17.2% in the development cohort and 22.3% in the validation cohort, missing between 1.8% and 2% of csPCa among men at risk of PCa. In summary, BCN-RC 1 can stratify initial PCa suspicion, reducing the demand of mpMRI, with an acceptable loss of csPCa.