Simple SummaryUS-MRI fusion biopsy is established as a technique of reference for the detection of clinically significative prostate cancer compared to the ultrasound “template” technique. Several software have been developed to aid clinicians to perform a real-time fusion between MRI and US prostate imaging; however, the images can also be mentally superimposed by the operator performing a cognitive fusion. Many papers in the literature describe the feasibility and efficacy of these two techniques, but few have performed a direct comparison between them. Therefore, we selected all comparative studies with the aim to perform a meta-analysis to find if one technique leads to an improvement in the detection rate of clinically significant prostate cancer (csPCa) for biopsies performed with a transperineal approach. Our findings indicate that csPCa detection is comparable between these techniques. Thus, clinicians can choose to perform a cognitive or software-assisted biopsy in accordance with their personal experience or technologic availability without the potential risk of offering an underperforming methodology.AbstractIntroduction: We aimed to find potential differences in clinically significant prostate cancer (csPCa) detection rates between transperineal software-assisted fusion biopsy (saFB) and cognitive fusion biopsies (cFB). Methods: A systematic review of the literature was performed to identify comparative studies using PubMed, EMBASE, and Scopus according to the PICOS criteria. Cancer detection and complication rates were pooled using the Cochran–Mantel–Haenszel method with the random effect model and reported as odds ratios (ORs), 95% confidence intervals (CI), andp-values. A meta-analysis was performed using Review Manager (RevMan) 5.4 software by Cochrane Collaboration. The quality assessment of the included studies was performed using the Cochrane Risk of Bias tool, using RoB 2 for randomized studies and ROBINS-I for retrospective and nonrandomized ones. Results: Eight studies were included for the meta-analysis, including 1149 cases in software-based and 963 cases in cognitive fusion biopsy. The detection rates of csPCa were similar between the two groups (OR 1.01, 95% CI 0.74–1.37,p= 0.95). Study heterogeneity was low (I2 55%). Conclusion: There is no actual evidence of the superiority of saFB over cFB in terms of the csPCa detection rate. Operator experience and software availability can drive the choice of one fusion technique over the other.