Does It Make Sense to Perform Prostate Magnetic Resonance Imaging in Men with Normal PSA (<4 ng/mL)?

<b>Objective</b>: We evaluate the performance and relevance of MRI to detect csPC in men with normal PSA. <b>Methods</b>: Out of our database of patients referred for prostate MRI, we selected men with PSA < 4 ng/mL for whom histopathology or at least 2 years of clinical follow-up data were available as standard of reference. Subgroup analyses were performed for the patients with PSA < 3 ng/mL, <2 ng/mL, and 2-3.9 ng/mL. The reasons for prostate MRI referral despite their normal PSA level were retrieved by exploring the patients' files. The prostate MRIs were reported according to the Prostate Imaging and Reporting Data System (PI-RADS), and the overall assessment score was registered. For evaluation of the performance, PI-RADS ≥ 3 was set as a threshold for a positive exam. The patients without PC or only International Society of Urological Pathology (ISUP) grade group 1 PC (Gleason 3+3) were considered as one category having no csPC. The performance of prostate MRI was separately evaluated for detection of ISUP ≥ 2 and for ISUP ≥ 3 csPC. <b>Results</b>: A total of 148 men were included, with PSA ranging from 0.42 to 3.99 ng/mL (median 2.95, IQR 1.68-3.50) and age ranging from 36 to 84 years (median 58, IQR 52-66). A total of 74 men (50.0%) had a PSA level < 3 ng/mL, 42 (28.4%) had a PSA level < 2 ng/mL, and 106 (71.6%) had a PSA level of 2-3.9 ng/mL. They were referred for prostate MRI for a wide variety, and usually a combination of, reasons, such as younger age (<60 years in 55.4%, N = 82; <50 years in 17.6%, N = 26), abnormal digital rectal examination in 31.8% of cases (N = 47), suspicious PSA dynamics in 29.7% (N = 44), positive familial history in 27.0% (N = 40), clinical signs of prostatitis in 18.2% (N = 27), suspicious findings on Transrectal Ultrasound (TRUS) in 16.9% (N = 25), hematospermia in 7.4% (N = 11), hematuria in 4.1% (N = 6), incidental hot spot in the prostate on Fluoro-Deoxy-Glucose (FDG) Positron Emission Tomography (PET)-Computed Tomography (CT) in 4.1% (N = 6), lymphadenopathies on CT in 2.7% (N = 4), or severe patient anxiety in 3.4% (N = 5). Overall, ISUP ≥ 2 PC was present in 18.9% (N = 28) of cases, and MRI detected this with a sensitivity of 92.9%, a specificity of 66.7%, and a positive predictive value of 39.4%. ISUP ≥ 3 PC was present in 9.5% (N = 14) of cases, and prostate MRI detected this with a sensitivity of 100%, a specificity of 61.2%, and a positive predictive value of 21.2%. In patients with PSA < 2 ng/mL (N = 42), no csPC was found, but MRI generated false positives in 33.3%. <b>Conclusions</b>: Performing prostate MRI in men with normal PSA (<4 ng/mL) seems useful if there are other reasons that increase the clinical suspicion of csPC. In about one-fifth of these patients, csPC is present and MRI has high sensitivity for its detection. Prostate MRI has, however, low positive predictive value in this patient group, and clinicians should be aware of the risk of false-positive MRI. Below a PSA level of 2 ng/mL, no csPC was found and prostate MRI generated only false positives, suggesting limited value in this subgroup.