Prostate cancer (PCa) is the most common type of cancer in men (1). Conventional methods for diagnosis of prostate cancer include prostate-specific antigen (PSA) blood examinations and digital rectal examination (DRE). Diagnosis using these two methods is confirmed through transrectal ultrasound(TRUS)-guided systematic prostate biopsy (SB) (2). However, low sensitivity and specificity of conventional TRUS-guided biopsy limits its application (3). In addition, TRUS-guided biopsy does not detect approximately 20% of significant PCa (csPCa) cases (4). Moreover, TRUS-guided biopsy over detects clinically insignificant PCa (cisPCa), increasing overtreatment and associated side events like erectile dysfunction and urinary incontinence (5).

Multiple methods have been developed based on MpMRI (multiparametric magnetic resonance imaging) to obtaining prostate biopsy cores. Currently, MRI-guided in-bore biopsies (within the MRI machine) are available, but they are costly and time consuming, particularly given the requirement of non-ferromagnetic biopsy instruments in the MRI setting (6). Cognitive fusion is a process where the examining specialist assesses MRI images before ultrasound (US)-guided assessment, reduces costs as well as the spatial correlation capacity (7). Therefore, platforms which allow instant mpMRI and US image fusion biopsy have several advantages, such as implementation outside the MRI setting, good spatial correlation and are not costly (8). MRI-TRUS fusion guided-targeted biopsy (MRI-TB) combines mpMRI’s high accuracy in lesion detection and characterization and cost-efficiency with the simple-to use TRUS-guided platforms for urologists (9, 10). A previous study reports that targeted biopsy using mpMRI-TRUS fusion enhances PCa detection, allowing sampling of sites at higher risk which could not be detected with TRUS alone (11). In addition, it reduces over detection of insignificant tumors, thus avoiding unwarranted radical treatment (11).

Several meta-analyses have been published on diagnostic approaches of prostate cancer (12, 13). However, they focused on evaluating diagnosis of clinically significant and insignificant PCa, excluding high-risk PCa and did not explore benefits of MRI-TB in combination with SB. High-risk prostate cancer is an aggressive disease characterized by relapse after definitive treatment (14). Therefore, the aim of this systematic review was to compare the detection rates of prostate cancer by MRI-TB or MRI-TB plus SB versus SB in men with high serum PSA levels and/or abnormal digital rectal examination, mainly for diagnosis of high-risk PCa.

Although TRUS-guided prostate biopsy is widely used for diagnosis of prostate cancer, it is not effective in determining tumor location (17). Furthermore, incidence of clinically relevant tumor false-negative biopsy using TRUS is approximately 47%, which can delay treatment of tumors with high Gleason scores (42). Multiparametric MRI comprises contrast-enhanced dynamic imaging, T2-weighted, and diffusion-weighted strategies, and is considered the most sensitive imaging approach for PCa detection (11). Prostate gland mp-MRI is a valuable imaging technique for patients that require targeted prostate biopsy as it effectively identifies higher grades and PCa volume compared with systematic 12-core prostate biopsy. Therefore, mp-MRI increases accuracy of prostate biopsy analysis by guiding clinicians to suspicious areas during biopsy rather than random sampling (19). The findings of this systematic review show that MRI-TRUS fusion biopsy diagnoses more clinically significant PCa and high-risk PCa compared with systematic biopsy, with lower rate of detection of clinically insignificant PCa, thus avoiding consequent overtreatment.

Analysis showed that MRI-TB has a higher detection rate of clinically significant PCa and high-risk PCa compared with traditional TRUS-guided biopsy. On the other hand, the rate of detection of clinically insignificant PCa using MRI-TB was lower compared with the rate of detection using traditional TRUS-guided biopsy. MRI/TRUS fusion biopsy did not show significant differences in overall PCa diagnosis compared with systematic biopsy. These results are consistent with previous findings that MRI-TB diagnoses more clinically significant PCa and fewer clinically insignificant PCa cases compared with standard biopsy (12, 13). Similarly, in the study carried out by Pepe et al., they included a total of 1032 patients suspicion of cancer and found that MRI targeted fusion biopsy had a lower detection rate of clinically insignificant prostate cancer than transperineal saturation biopsy (43). However, the previous systematic reviews did not explore the detection rate of MRI-TB for high-risk PCa. Currently, very few systematic reviews and meta-analyses have explored detection rate of high-risk PCa using MRI-TB. Similar findings were reported by Tang et al. on high-risk PCa detection, however, meta-analysis mainly evaluated MRI/TRUS fusion 3D model-guided targeted biopsy for PCa (44). Patients with high-risk prostate cancer are at an increased risk of biochemical recurrence, metastatic progression and cancer-related death following primary treatment compared with patients with low-risk or intermediate-risk disease (45). Individuals with high-risk PCa have high risk of systemic or local relapse and are more likely to experience symptoms and/or higher risk of death (17). Therefore, we explored high-risk PCa detection in the present meta-analysis. Our findings show that MRI-TB may help clinicians to effectively screen high-risk PCa, thus improving treatment decisions, which are consistent with previous findings (27).

Analysis of the 3 PCa diagnosis methods (including MRI-TB combined with SB) showed that MRI-TB+SB was superior in detection of overall, clinically significant, and high-risk PCa, which was consistent with reports from previous studies (23, 27–30). Rapisarda et al. compared the coincidence rate in the detection of clinically significant PCa cancers (GS≥7) between combined biopsy (fusion plus standard) and final histological report to 73.6%. They suggest that targeted biopsy combined with systematic biopsy can further improve the detection rate of clinically significant prostate cancer and reduce the missed diagnosis rate with targeted biopsy alone (46). This observation coincides with our findings.However, MRI-TB+SB did not exhibit significantly different diagnostic rate for clinically insignificant PCa compared with SB method. Therefore, MRI-TB+SB did not reduce detection of clinically insignificant PCa compared with SB.

This review had a few limitations. Firstly, most of the included studies had paired designs, therefore, the analysis introduces bias because conclusions from such data are limited to MRI patients with suspicious findings using MRI-TB, and systematic biopsy. Secondly, MRI image quality and definitions of clinically significant and high-risk PCa were different across centers, causing heterogeneity. Finally, integrating MRI-TB with SB improves rate of detection of overall clinically significant cases, and high-risk PCa case compared with other biopsy methods. However, MRI-TB+SB needs more biopsy cores. Therefore, further studies should be performed to determine MRI-TB+SB results in more complications compared with systematic biopsy.

Finally, we note some new directions in PCa research and give an outlook to the future research. Recently, radiomics and genomics have increasingly become a prospective topic in the field of prostate cancer research. A combination of these fields, radiogenomics, is an emerging fifield that studies the correlation between image phenotypes and genomics inside a tumor. Prostate cancer has been extensively investigated using radiogenomics, with experiments between quantitative image features and single gene expression, which have yielded promising results (47). Some studies showed that radiomic features correlation with Gleason score and PIRADS sum scores (48–50). In the detection of clinically significant PCa, Combining radiological and clinical radiomic models was indeed effective in predicting clinically significant PCa in patients with a PIRADS score of three or more. It is possible to further improve the radiomic potential of this issue by developing different models automatically, using machine learning and artificial intelligence techniques, and by creating nomograms (51). However, At present, radiogenomics holds great promise, but it is a new area of research, the use of radiogenomics in clinical practice regarding prostate cancer does not have any utility or effectiveness.We need to fill many gaps to achieve clinical implementation of radiogenomics.

The findings of this study show that MRI-TB has higher detection rate for clinically significant and high-risk PCa cases, and fewer rate for clinically insignificant PCa cases compared with systematic protocols. Combination of MRI-TB with SB improves PCa detection in compared with use of either of the methods alone. However, MRI-TB+SB does not reduce the diagnosis rate of clinically insignificant PCa. The findings of this study provide information for clinicians and patients on the risks and benefits of using MRI-TB or systematic biopsy.

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.

JX and CJ have contributed equally. JX, conception, manuscript preparation, data collection and analysis. CJ, conception, data analysis, manuscript editing and manuscript review. ML, Study design, manuscript editing and manuscript review. KS, study design and manuscript review. ZJ, data collection and analysis. ZD and XG, substantial contributions, manuscript editing and manuscript review. All authors contributed to the article and approved the submitted version.

This study was supported by grants from Shenzhen Science and Technology Innovation Committee (JCYJ20170413161913429), Shenzhen Key Medical Discipline Construction Fund (SZXK052) and Sanming Project of Medicine in Shenzhen (SZSM201612027).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.