Prostate Cancer and Prostatic Diseases (2021) 24:1103–1109 https://doi.org/10.1038/s41391-021-00366-9 ARTICLE Clinical Research Diagnostic yield of fusion magnetic resonance-guided prostate biopsy versus cognitive-guided biopsy in biopsy-naive patients: a head-to-head randomized controlled trial Mohammad-Hossein Izadpanahi 1 ● Amirreza Elahian 2 ● Farshad Gholipour 3 ● Mohammad-Hatef Khorrami 1 ● Mahtab Zargham 1 ● Mehrdad Mohammadi Sichani 1 ● Farshid Alizadeh 1 ● Farbod Khorrami 4 Received: 11 October 2020 / Revised: 25 February 2021 / Accepted: 26 March 2021 / Published online: 27 April 2021 © The Author(s), under exclusive licence to Springer Nature Limited 2021 Abstract Background The combination of MRI-guided targeted biopsy (MRGB) with systematic biopsy (SB) provides the highest accuracy in detecting prostate cancer. There is a controversy over the superiority of fusion targeted biopsy (fus-MRGB) over cognitive targeted biopsy (cog-MRGB). The present head-to-head randomized controlled trial was performed to compare diagnostic yield of fus-MRGB in combination with SB with cog-MRGB in combination with SB. Methods Biopsy-naive patients with a prostate-specific antigen level between 2 and 10 ng/dL who were candidates for prostate biopsy were included in the study. Multiparametric MRI was performed on all patients and patients with suspicious lesions with Prostate Imaging Reporting and Data System score of 3 or more were randomized into two groups. In the cog- MRGB group, a targeted cognitive biopsy was performed followed by a 12-core SB. Similarly, in the fus-MRGB group, first targeted fusion biopsy and then SBs were performed. The overall and clinically significant prostate cancer detection rates between the two study groups were compared by the Pearson χ 2 test. McNemar test was used to compare detection rates yielded by SB and targeted biopsy in each study group. Results One-hundred men in the cog-MRGB group and 99 men in the fus-MRGB group were compared. The baseline characteristics of patients including age, PSA level, prostate volume, PSA density, and clinical stage were similar in the two groups (p > 0.05). Both the overall and clinically significant prostate cancer detection rates in the fus-MRGB group (44.4% and 33.3%, respectively) were significantly higher than cog-MRGB group (31.0% and 19.0%, respectively) (p = 0.035 and p = 0.016, respectively). Conclusion The accuracy of identifying overall and clinically significant prostate cancer by fus-MRGB in biopsy-naive patients with PSA levels between 2 and 10 ng/dL is significantly higher than cog-MRGB and if available, we recommend using fus-MRGB over cog-MRGB in these patients. Introduction Management of prostate cancer (PCa) is among the most challenging tasks in urology. In the majority of cases, a prostate biopsy is the prominent determinant of the next steps in disease management. The introduction of multi- parametric magnetic resonance imaging (mpMRI) as a guiding tool for increasing the precision of prostate biopsy is one of the most revolutionary technological advance- ments in the field of prostate biopsy [1–7]. Magnetic resonance-guided biopsy (MRGB) can be performed using an in-bore system (i.e., in-bore-MRGB) or by registration of MRI on ultrasonography images. Registration can be done by cognitive (cog-) or software-based fusion (fus-) MRGB [8–10]. Cognitive (or visual) registration is the most * Farshad Gholipour gholipour@med.mui.ac.ir 1 Department of Urology, Al-Zahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran 2 Department of Urology, Iran University of Medical Sciences, Tehran, Iran 3 Isfahan Kidney Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran 4 Department of Human Biology, University of Toronto, Toronto, ON, Canada 1234567890();,: 1234567890();,: