MCO Molecular and Clinical Oncology 2049-9450 2049-9469 D.A. Spandidos 10.3892/mco.2016.906 MCO-0-0-906 Articles Magnetic resonance imaging - ultrasound fusion targeted biopsy outperforms standard approaches in detecting prostate cancer: A meta-analysis JiangXuping 1 2 * ZhangJiayi 2 * TangJingyuan 2 XuZhen 2 ZhangWei 2 ZhangQing 3 GuoHongqian 3 ZhouWeimin 1 Department of Urology, Yixing People's Hospital, Yixing, Jiangsu 214200, P.R. China State Key Laboratory of Reproductive Medicine, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China Correspondence to: Dr Weimin Zhou, Department of Urology, Yixing People's Hospital, 75 Tong Zhen Guan Road, Yixing, Jiangsu 214200, P.R. China, E-mail: doctor-zhouwm@163.com

Contributed equally

 08 2016 20 05 2016 5 2 301 309 12022016 09052016 Copyright: © Jiang et al. 2016 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

The aim of the present study was to determine whether magnetic resonance imaging - ultrasound (MRI-US) fusion prostate biopsy is superior to systematic biopsy for making a definitive diagnosis of prostate cancer. The two strategies were also compared regarding their ability to detect clinically significant and insignificant prostate cancer. A literature search was conducted through the PubMed, EMBASE and China National Knowledge Infrastructure databases using appropriate search terms. A total of 3,415 cases from 21 studies were included in the present meta-analysis. Data were expressed as relative risk (RR) and 95% confidence interval. The results revealed that MRI-US fusion biopsy achieved a higher rate of overall prostate cancer detection compared with systematic biopsy (RR=1.09; P=0.047). Moreover, MRI-US fusion biopsy detected more clinically significant cancers compared with systematic biopsy (RR=1.22; P<0.01). It is therefore recommended that multi-parametric MRI-US is performed in men suspected of having prostate cancer to optimize the detection of clinically significant disease, while reducing the burden of biopsies.

 fusion image magnetic resonance imaging prostate cancer targeted biopsy meta-analysis Introduction

Prostate cancer is currently one of the most common malignant tumors in men aged >50 years. The global age-standardized incidence rate of prostate cancer in 2008 was ~30/100,000 individuals, which is second only to that of lung cancer (1). Screening for prostate cancer mostly relies on digital rectal examination, measurement of prostate-specific antigen (PSA) level, magnetic resonance imaging (MRI) and ultrasound (US). The current standard for diagnosing prostate cancer in men at risk relies on a transrectal US (TRUS)-guided biopsy test, which is blind to cancer location. This method has the advantages of speed, ease, cost-effectiveness, availability and portability, and it is more suitable for wide-area sampling of the prostate, including the far-lateral peripheral zones (2). However, despite an increasing number of biopsy cores being included in TRUS-guided biopsy protocols, the current standard of including 10–14 randomized cores lacks sensitivity and frequently detects clinically insignificant disease (3–5).

It was recently suggested that targeted biopsies of suspicious lesions detected by multi-parametric (mp)-MRI may increase the diagnostic accuracy of TRUS-guided biopsy (6). mp-MRI combines T2-weighted images with diffusion-weighted images and dynamic contrast enhancement (7,8). This method exhibits increased sensitivity and specificity and has become the standard imaging technique for biopsy guidance (9,10). As mp-MRI and biopsy are performed on different days, with the latter commonly performed using a TRUS probe, a number of devices that use image-fusion software have been developed to overlay the suspicious area on mp-MRI onto the US images at the time of biopsy (11).

In the present study, a meta-analysis of data extracted from published studies using MRI-US image fusion targeted prostate biopsy was performed to assess the accuracy of prostate cancer detection compared with that of systematic biopsy.

 Materials and methods <sec> <title>Literature search strategy

A literature search was conducted through the PubMed, EMBASE and China National Knowledge Infrastructure databases for studies published prior to July 21st, 2015, using the key words (‘prostate cancer’, ‘prostate neoplasm’ or ‘prostate’) in combination with (‘magnetic resonance imaging’, ‘MRI’ or ‘MR’) and (‘transrectal ultrasound’ or ‘TRUS’) and (‘fusion’, ‘registration’, ‘targeted’, ‘target’, ‘computer’ or ‘software’). Only articles written in English or Chinese and studies on human subjects were included. In addition, references of relevant articles were manually searched to identify potentially eligible studies.

 Eligibility criteria

Two authors assessed each identified study independently. The inclusion of individual studies required that software-based MRI-US fusion targeted prostate biopsies and systematic biopsies had been performed within the same study. In addition, each study was required to contain overall or significant cancer detection results for the two modalities. To allow for a valid comparison, only studies directly comparing the two techniques were included. When multiple studies contained overlapping data, only the most informative study was included. Meeting abstracts, editorials, case reports, letters and reviews were excluded.

 Data extraction

Two investigators blinded to each others' results independently reviewed the full manuscripts of the eligible studies. The information extracted from each study included first author, year of publication, study design, population (sample size, age, PSA, prostate volume and prior biopsy), type of anaesthesia, systematic biopsy (number of cores and sampling route), MRI-US image fusion targeted biopsy procedure (software used, sampling route, time flow and number of cores per lesion) and separate histological outcomes for systematic vs. targeted biopsy (overall detection rate of cancer and detection rate of clinically significant and insignificant cancer). Disagreements between the two reviewers were resolved through discussion.

 Statistical analysis

All the analyses were performed using the statistical Stata software, version SE/12 (StataCorp LP, College Station, TX, USA). The main outcome was the detection rate of overall prostate cancer and the secondary outcomes were the detection rates of clinically significant and insignificant disease by MRI-TRUS image fusion targeted biopsy compared with the systematic biopsy technique. The definition used to determine clinical significance was that used by each individual study. Fixed-effects or random-effects meta-analysis was performed to pool the original studies on the basis of their relative risk (RR), depending on the result of the heterogeneity analysis. Forest plots were created to summarize all studies, the pooled estimate and corresponding 95% confidence intervals (95% CIs) in a single overview.

Heterogeneity was assessed using the I2 statistical method, with I2>50% indicating significant heterogeneity. When heterogeneity was confirmed, a sensitivity analysis was performed by successively excluding each individual study. Subgroup analysis was performed according to several characteristics. Publication bias was assessed using Begg's funnel plot and Egger's test. All the P-values were two-tailed and P<0.05 was considered to indicate statistically significant differences.

 Results <sec> <title>Study selection and characteristics

Of the 800 articles retrieved during the initial search, 21 (2,12–31) met the inclusion criteria. A flow chart of the study selection process is presented in Fig. 1.

A total of 3,415 patients were included, with a sample size ranging from 20 to 1,003 patients. The majority of studies originated from 6 countries, with studies from the USA comprising the largest proportion (n=10). A total of 6 studies had been conducted on biopsy-naive patients, 4 on patients with a previous negative prostate biopsy, and 11 studies reported on a mixed cohort (either biopsy-naive patients, or those having undergone previous prostate biopsy). All mp-MRI scans had been performed on either a 1.5- or a 3-T scanner and 9 different image fusion platforms currently used in the clinical setting to perform MRI-TRUS targeted biopsies were identified in this meta-analysis. The standard comparator was a 8- to 12-core TRUS biopsy in 18 studies, whereas 3 other studies used transperineal template biopsies, or a combination of the two. The characteristics of the included studies are summarized in Table I.

 Overall prostate cancer detection

Details regarding diagnostic criteria and detection ratios in the individual studies are presented in Table II. Across the 21 studies, the prevalence of prostate cancer was 63.0% (2,153/3,415). MRI-US fusion biopsy detected overall prostate cancer in 1,562 of 3,315 patients and systematic biopsy in 1,496 of 3,313 patients, resulting in an RR of 1.09 (95% CI: 1.00–1.18; P=0.047) (Fig. 2). The heterogeneity among these studies was moderate (I2=47.8%; χ2=38.34; P=0.047). Publication bias in this overall analysis was revealed by the Begg's funnel plot (P=0.205, Begg's test; P=0.017, Egger's test) (Fig. 3).

 Clinically significant prostate cancer detection

A total of 14 studies including 1,884 patients were eligible for inclusion in the analysis. The prevalence of clinically significant and insignificant prostate cancer was 47.2% (890/1,884) and 16.6% (313/1,884), respectively. Clinically significant prostate cancer was diagnosed in 721 of the 1,795 patients with MRI-US fusion biopsy compared with 608 of 1,793 patients with systematic biopsy, with an RR of 1.22 (95% CI: 1.06–1.40; P=0.005) (Fig. 4). However, heterogeneity was observed among these studies (I2=56.7%; χ2=30.04; P=0.005). Begg's funnel plots revealed little publication bias in this analysis (Fig. 5), whereas the Egger's and Begg's tests indicated there was no publication bias.

The results of the subgroup analysis for clinically significant prostate cancer detection are presented in Table III. MRI-US fusion biopsy exhibited a significantly higher detection rate of clinically significant prostate cancer compared with systematic biopsy in 7 subgroups, but there was heterogeneity in all subgroups apart from that of patients with a previous negative biopsy.

Sensitivity analysis of the 14 studies demonstrated that the results of Kuru et al (28) diverged from those of most other trials (Fig. 6). Following exclusion of the Kuru et al trial, there was no significant variation in the RR value, but the heterogeneity decreased (Table IV).

Clinically insignificant prostate cancer was diagnosed in 178 of 1,795 patients by MRI-US fusion biopsy and in 256 of 1,793 patients by systematic biopsy, resulting in a RR of 0.73 (95% CI: 0.51–1.05; P=0.089); there was high heterogeneity among these studies (I2=67.5%; χ2=39.97; P<0.01).

 Discussion

The current gold standard technique for diagnosing prostate cancer in men at risk is systematic prostate biopsy using TRUS. However, there are discrepancies between the results of systematic prostate biopsy and radical prostatectomy specimens (32), as only 24–40% of TRUS-guided biopsy results are consistent with the pathological findings following prostatectomy (33). Furthermore, systematic biopsy may not be able to detect all cases of clinically significant prostate cancer, which may delay the treatment of a tumor with a high Gleason score (3–5). The optimal biopsy strategy should selectively detect clinically significant prostate cancer and minimize clinically insignificant prostate cancer detection to avoid consequent overtreatment. The present meta-analysis demonstrated that MRI-US fusion targeted biopsy may be a promising strategy with certain advantages over systematic biopsy.

The results of the present study demonstrated that the overall prostate cancer detection rate of MRI-US fusion biopsy is higher compared with that of systematic biopsy, with an RR of 1.09. The difference between the results of the present study and those of a prior systematic review (34) may be due to the larger sample size and updated data included herein.

It was reported that mp-MRI exhibits a high diagnosis rate of clinically significant prostate cancer when compared to the histological findings following radical prostatectomy (35), which is in line with the results of the present study. In our study, MRI-US fusion biopsy had an RR of 1.22 for detecting significant prostate cancer, which means that MRI-US fusion biopsy has a 22% increased detection rate for clinically significant prostate cancer compared with systematic biopsy.

MRI-US fusion biopsy and systematic biopsy did not significantly differ in the detection of clinically insignificant prostate cancer; however, an RR of 0.73 indicated that MRI-US had a better performance in terms of avoiding detection of insignificant prostate cancer compared with systematic biopsy in most studies. Thus, the application of MRI-US fusion biopsy may help reduce oversampling of potentially insignificant prostate cancers.

Several studies also compared MRI-US fusion with the systematic approach on a per-core basis (13,21,30). The results demonstrated that MRI-US-guided biopsy required fewer cores for successful tumor detection, thereby reducing patient discomfort compared with systematic biopsy.

The present meta-analysis had several limitations that may reduce the strength of the conclusions. Studies with negative results are less likely to be published, which may result in the overstatement of beneficial effects in meta-analyses. In the analysis of the overall prostate cancer detection rate, Begg's test yielded a P-value of 0.205, while Egger's test yielded a P-value of 0.017, indicating the presence of publication bias, as Egger's test has a higher sensitivity.

In the analysis of the detection of clinically significant prostate cancer, Begg's test and Egger's test indicated no publication bias. However, significant heterogeneity was found in this analysis (I2=56.7%). Subgroup analysis revealed the presence of heterogeneity in all subgroups apart from that including patients with a previous negative biopsy, indicating that the heterogeneity originated in the category of prior biopsy, but not study design, main race, strength of magnetic field or sampling method. The sensitivity analysis revealed that, after excluding the trial by Kuru et al (28), heterogeneity was markedly decreased, while the RR value was not significantly affected. Kuru et al (28) obtained a higher RR compared with that of the other studies, possibly due to the BiopSee system used in their study, in which US, TRUS/MRI fusion, biopsy planning, perineal targeting, 3D mapping and automated documentation are integrated into a single system. The definition of significant prostate cancer, which included intermediate or high-risk tumors according to the National Comprehensive Cancer Network criteria (36), may also explain their higher RR. In addition, significant heterogeneity may be attributed to the variability across the studies in terms of criteria for defining clinically significant tumors, the methodology of targeted biopsy and the number of cores per target.

On the basis of biopsy data alone, it may be methodologically incorrect to conclude that MRI-US fusion biopsy detects more significant prostate cancers compared with systematic biopsy. This conclusion may be a statistical or methodological effect rather than a true clinical fact. All patients would have to undergo radical prostatectomy and assessment of the final pathology to draw clinically relevant conclusions. Such studies are warranted in the future.

In summary, a meta-analysis of the currently available high-level clinical studies was performed to evaluate the efficacy of MRI-US fusion prostate biopsy. It was revealed that MRI-US fusion prostate biopsy has a higher detection rate of prostate cancer compared with systematic biopsy. MRI-US fusion biopsy also detects more clinically significant and fewer insignificant prostate cancers compared with systematic protocols. It is therefore recommended that mp-MRI is performed in patients suspected of having prostate cancer in order to optimize the detection of clinically significant prostate cancer, while reducing the burden of biopsies.

 Acknowledgements

The present study was supported by the National Natural Science Foundation of China (grant no. 81370781).

 References SoerjomataramILortet-TieulentJParkinDMFerlayJMathersCFormanDBrayFGlobal burden of cancer in 2008: A systematic analysis of disability-adjusted life-years in 12 world regionsLancet38018401850201210.1016/S0140-6736(12)60919-223079588 MiyagawaTIshikawaSKimuraTSuetomiTTsutsumiMIrieTKondohMMitakeTReal-time virtual sonography for navigation during targeted prostate biopsy using magnetic resonance imaging dataInt J Urol17855860201010.1111/j.1442-2042.2010.02612.x20807266 BabaianRJToiAKamoiKTroncosoPSweetJEvansRJohnstonDChenMA comparative analysis of sextant and an extended 11-core multisite directed biopsy strategyJ Urol163152157200010.1016/S0022-5347(05)67993-110604335 PrestiJCJrO'DowdGJMillerMCMattuRVeltriRWExtended peripheral zone biopsy schemes increase cancer detection rates and minimize variance in prostate specific antigen and age related cancer rates: Results of a community multi-practice studyJ Urol169125129200310.1016/S0022-5347(05)64051-712478119 Campos-FernandesJLBastienLNicolaiewNRobertGTerrySVacherotFSalomonLAlloryYVordosDHoznekAProstate cancer detection rate in patients with repeated extended 21-sample needle biopsyEur Urol55600606200910.1016/j.eururo.2008.06.04318597923 SonnGAMargolisDJMarksLSTarget detection: Magnetic resonance imaging-ultrasound fusion-guided prostate biopsyUrol Oncol32903911201410.1016/j.urolonc.2013.08.00624239473 DickinsonLAhmedHUAllenCBarentszJOCareyBFuttererJJSalomonLAlloryYVordosDHoznekAMagnetic resonance imaging for the detection, localisation, and characterisation of prostate cancer: Recommendations from a European consensus meetingEur Urol59477494201110.1016/j.eururo.2010.12.00921195536 BarentszJORichenbergJClementsRChoykePVermaSVilleirsGRouviereOLogagerVFüttererJJEuropean Society of Urogenital Radiology: ESUR prostate MR guidelines 2012Eur Radiol22746757201210.1007/s00330-011-2377-y22322308 HaffnerJLemaitreLPuechPHaberGPLeroyXJonesJSVillersARole of magnetic resonance imaging before initial biopsy: Comparison of magnetic resonance imaging-targeted and systematic biopsy for significant prostate cancer detectionBJU Int108E171E178201110.1111/j.1464-410X.2011.10112.x21426475 HambrockTSomfordDMHoeksCBouwenseSAHuismanHYakarDvan OortIMWitjesJAFüttererJJBarentszJOMagnetic resonance imaging guided prostate biopsy in men with repeat negative biopsies and increased prostate specific antigenJ Urol183520527201010.1016/j.juro.2009.10.02220006859 MooreCMRobertsonNLArsaniousNMiddletonTVillersAKlotzLTanejaSSEmbertonMImage-guided prostate biopsy using magnetic resonance imaging-derived targets: A systematic reviewEur Urol63125140201310.1016/j.eururo.2012.06.00422743165 SankineniSGeorgeAKBrownAMRais-BahramiSWoodBJMerinoMJPintoPAChoykePLTurkbeyBPosterior subcapsular prostate cancer: Identification with mpMRI and MRI/TRUS fusion-guided biopsyAbdom Imaging4025572565201510.1007/s00261-015-0426-825916869 ZhangQWangWYangRZhangGZhangBLiWHuangHGuoHFree-hand transperineal targeted prostate biopsy with real-time fusion imaging of multiparametric magnetic resonance imaging and transrectal ultrasound: Single-center experience in ChinaInt Urol Nephrol47727733201510.1007/s11255-015-0957-525820744 de GorskiARouprêtMPeyronnetBLe CossecCGrangerBComperatECussenotOAccuracy of magnetic resonance imaging/ultrasound fusion targeted biopsies to diagnose clinical significant prostate cancer in enlarged compared to smaller prostatesJ Urol194669673201510.1016/j.juro.2015.03.02525784374 UkimuraOMarienAPalmerSVillersAAronMde CastroAALeslieSShojiSMatsugasumiTGrossMTrans-rectal ultrasound visibility of prostate lesions identified by magnetic resonance imaging increases accuracy of image-fusion targeted biopsiesWorld J Urol3316691676201510.1007/s00345-015-1501-z25656687 JunkerDSchäferGHeideggerIBekticJLadurnerMJaschkeWAignerFMultiparametric magnetic resonance imaging/transrectal ultrasound fusion targeted biopsy of the prostate: Preliminary results of a prospective single-centre studyUrol Int94313318201510.1159/00036548925591786 ShojiSHiraiwaSEndoJHashidaKTomonagaTNakanoMSugiyamaTTajiriTTerachiTUchidaTManually controlled targeted prostate biopsy with real-time fusion imaging of multiparametric magnetic resonance imaging and transrectal ultrasound: An early experienceInt J Urol22173178201510.1111/iju.1264325316213 SalamiSSBen-LeviEYaskivORynikerLTurkbeyBKavoussiLRVillaniRRastinehadARIn patients with a previous negative prostate biopsy and a suspicious lesion on magnetic resonance imaging, is a 12-core biopsy still necessary in addition to a targeted biopsy?BJU Int115562570201510.1111/bju.1293825252133 MozerPRouprêtMLe CossecCGrangerBComperatEde GorskiACussenotORenard-PennaRFirst round of targeted biopsies using magnetic resonance imaging/ultrasonography fusion compared with conventional transrectal ultrasonography-guided biopsies for the diagnosis of localised prostate cancerBJU Int1155057201510.1111/bju.1269024552477 RastinehadARTurkbeyBSalamiSSYaskivOGeorgeAKFakhouryMBeecherKViraMAKavoussiLRSiegelDNImproving detection of clinically significant prostate cancer: Magnetic resonance imaging/transrectal ultrasound fusion guided prostate biopsyJ Urol19117491754201410.1016/j.juro.2013.12.00724333515 FiardGHohnNDescotesJLRambeaudJJTroccazJLongJATargeted MRI-guided prostate biopsies for the detection of prostate cancer: Initial clinical experience with real-time 3-dimensional transrectal ultrasound guidance and magnetic resonance/transrectal ultrasound image fusionUrology8113721378201310.1016/j.urology.2013.02.02223540865 VourgantiSRastinehadAYerramNKNixJVolkinDHoangATurkbeyBGuptaGNKrueckerJLinehanWMMultiparametric magnetic resonance imaging and ultrasound fusion biopsy detect prostate cancer in patients with prior negative transrectal ultrasound biopsiesJ Urol18821522157201210.1016/j.juro.2012.08.02523083875 DelongchampsNBPeyromaureMSchullABeuvonFBouazzaNFlamTZerbibMMuradyanNLegmanPCornudFPrebiopsy magnetic resonance imaging and prostate cancer detection: Comparison of random and targeted biopsiesJ Urol189493499201310.1016/j.juro.2012.08.19522982424 PuechPRouvièreORenard-PennaRVillersADevosPColombelMBitkerMOLeroyXMège-LechevallierFComperatEProstate cancer diagnosis: Multiparametric MR-targeted biopsy with cognitive and transrectal US-MR fusion guidance versus systematic biopsy-prospective multicenter studyRadiology268461469201310.1148/radiol.1312150123579051 VolkinDTurkbeyBHoangANRais-BahramiSYerramNWalton-DiazANixJWWoodBJChoykePLPintoPAMultiparametric magnetic resonance imaging (MRI) and subsequent MRI/ultrasonography fusion-guided biopsy increase the detection of anteriorly located prostate cancersBJU Int114E43E49201410.1111/bju.1267024712649 SonnGAChangENatarajanSMargolisDJMacairanMLieuPNixJWWoodBJChoykePLPintoPAValue of targeted prostate biopsy using magnetic resonance-ultrasound fusion in men with prior negative biopsy and elevated prostate-specific antigenEur Urol65809815201410.1016/j.eururo.2013.03.02523523537 WysockJSRosenkrantzABHuangWCStifelmanMDLeporHDengFMMelamedJTanejaSSA prospective, blinded comparison of magnetic resonance (MR) imaging-ultrasound fusion and visual estimation in the performance of MR-targeted prostate biopsy: The PROFUS trialEur Urol66343351201410.1016/j.eururo.2013.10.04824262102 KuruTHRoethkeMCSeidenaderJSimpfendörferTBoxlerSAlammarKRiekerPPopeneciuVIRothWPahernikSCritical evaluation of magnetic resonance imaging targeted, transrectal ultrasound guided transperineal fusion biopsy for detection of prostate cancerJ Urol19013801386201310.1016/j.juro.2013.04.04323608676 BacoERudEEriLMMoenGVlatkovicLSvindlandAEggesbøHBUkimuraOA randomized controlled trial to assess and compare the outcomes of two-core prostate biopsy guided by fused magnetic resonance and transrectal ultrasound images and traditional 12-core systematic biopsyEur Urol69149156201610.1016/j.eururo.2015.03.04125862143 SiddiquiMMRais-BahramiSTurkbeyBGeorgeAKRothwaxJShakirNOkoroCRaskolnikovDParnesHLLinehanWMComparison of MR/ultrasound fusion-guided biopsy with ultrasound-guided biopsy for the diagnosis of prostate cancerJAMA313390397201510.1001/jama.2014.1794225626035 BorkowetzAPlatzekITomaMLaniadoMBarettonGFroehnerMKochRWirthMZastrowSComparison of systematic transrectal biopsy to transperineal magnetic resonance imaging/ultrasound-fusion biopsy for the diagnosis of prostate cancerBJU Int116873879201510.1111/bju.1302325523210 PloussardGSalomonLXylinasEAlloryYVordosDHoznekAAbbouCCde la TailleAPathological findings and prostate specific antigen outcomes after radical prostatectomy in men eligible for active surveillance - does the risk of misclassification vary according to biopsy criteria?J Urol183539544201010.1016/j.juro.2009.10.00920006888 Dominguez-EscrigJLMcCrackenSRGreeneDBeyond diagnosis: Evolving prostate biopsy in the era of focal therapyProstate Cancer2011386207201110.1155/2011/38620722110983 ValerioMDonaldsonIEmbertonMEhdaieBHadaschikBAMarksLSMozerPRastinehadARAhmedHUDetection of clinically significant prostate cancer using magnetic resonance imaging-ultrasound fusion targeted biopsy: A systematic reviewEur Urol68819201510.1016/j.eururo.2014.10.02625454618 PuechPPotironELemaitreLLeroyXHaberGPCrouzetSKamoiKVillersADynamic contrast-enhanced-magnetic resonance imaging evaluation of intraprostatic prostate cancer: Correlation with radical prostatectomy specimensUrology7410941099200910.1016/j.urology.2009.04.10219773038 CarrollPRParsonsJKAndrioleGBahnsonRRCastleEPCatalonaWJDahlDMDavisJWEpsteinJIEtzioniRBNCCN Guidelines Insights: Prostate Cancer Early Detection, Version 2.2016J Natl Compr Canc Netw14509519201627160230

Flow chart of the study selection process. CNKI, China National Knowledge Infrastructure.

Forest plots of the RR with 95% CI for the heterogeneity of overall prostate cancer detection (MRI-US fusion biopsy vs. systematic biopsy) determined by the random-effects model. χ2=38.34, P=0.008, I2=47.8%, Z=1.99 and P=0.047. The grey square indicates the value of RR and its size is inversely proportional to its variance. The horizontal line represents the 95% CI of the RR. The white diamond represents the pooled results. The studies are ordered by the publication year. RR, relative risk; CI, confidence interval; MRI, magnetic resonance imaging; US, ultrasound.

Begg's funnel plot for the assessment of publication bias for overall prostate cancer detection. Begg's test, P=0.205; Egger's test, P=0.017. The horizontal line represents the summary estimate, while the sloping lines represent the expected 95% confidence interval. The case numbers in Wysock's and Delongchamps's studies were identical, leading to the superposition of the respective circles in the funnel plot. logES, natural logarithm of effect size; SE, standard error.

Forest plots of the RR with 95% CI for the heterogeneity of clinically significant prostate cancer detection (MRI-US fusion biopsy vs. systematic biopsy) determined by the random-effects model. χ2=30.04, P=0.005, I2=56.7%, Z=2.79 and P=0.005. The grey square indicates the value of RR and the size of the square is inversely proportional to its variance. The horizontal line represents the 95% CI of the RR. Tthe white diamond indicates the pooled results. The studies are ordered by publication year. RR, relative risk; CI, confidence interval; MRI, magnetic resonance imaging; US, ultrasound.

Begg's funnel plot for the assessment of publication bias for clinically significant prostate cancer detection. Begg's test, P=0.274; Egger's test, P=0.124. The horizontal line represents the summary estimate, while the sloping lines represent the expected 95% confidence interval. logES, natural logarithm of effect size; SE, standard error.

Sensitivity analysis of the RR with 95% CI of clinically significant prostate cancer detection (MRI-US fusion biopsy vs. systematic biopsy). The circles represent the RR estimate and the horizontal lines represent the 95% CI. The studies are ordered by publication year. MRI, magnetic resonance imaging; US, ultrasound; CI, confidence interval; RR, relative risk.

Main characteristics of the studies included in the meta-analysis.

Population characteristics MRI-TRUS fusion targeted biopsy
Author, year (Refs.) Study design Country Sample size (n) Age (years) PSA (ng/ml) Prostate volume (ml) Prior biopsy Anaesthesia System biopsy Magnetic field (T) Software used Sampling method Targeted biopsy first No. of cores per lesion
Baco et al 2015 (29) RCT USA 175 Mean (range), 65 (59–69) Mean (range), 7.3 (5.5–9.9) Mean (range), 42 (30–59) Biopsy naive Local TRUS 12 cores 1.5 UroStation Transrectal Yes Med (range), 2 (1–4)
Siddiqui et al 2015 (30) Cohort USA 1003 Mean ± SD, 62.1±7.5 Med (IQR), 6.7 (4.4–10.7) Med (IQR), 49 (36–71) Mixed NR TRUS 12 cores 3 UroNav Transrectal Yes 2
Borkowetz et al 2015 (31) Cohort Germany 263 Med (range), 66 (47–83) Med (range), 8.3 (0.39–86.57) Med (range), 50 (12–220) Mixed General or spinal TRUS 12 cores 3 Biojet Transperineal Yes ≥2
Sankineni et al 2015 (12) Cohort USA 33 Mean (range), 63 (52–76) Mean (range), 8.4 (1.22–65.20) Mean (range), 53 (12–125) Mixed NR TRUS 12 cores 3 UroNav Transrectal NR NR
Zhang et al 2015 (13) Cohort China 62 Mean ± SD, 68.38±6.57 Mean ± SD, 10.21±5.57 Mean ± SD, 34.05±9.86 Biopsy naive General TRUS 12 cores 3 RVS Transrectal Yes ≥2
de Gorski et al 2015 (14) Cohort France 232 Mean ± SD, 64±6.4 Mean ± SD, 6.65±1.8 Mean ± SD, 40±24.3 Biopsy naive NR TRUS 12 cores 1.5 UroStation Transrectal No NR
Ukimura et al 2015 (15) Cohort USA 127 Med, 69 Med, 5.8 NR Mixed Local TRUS 10–12 cores 3 UroStation Transrectal No ≥1
Junker et al 2015 (16) Cohort Australia 50 Mean ± SD, 63.7±7.9 Mean ± SD, 7.6±4.2 Mean ± SD, 49.2±21.9 Mixed NR TRUS 10 cores 3 Logiq Transrectal Yes Mean, 3.9
Shoji et al 2015 (17) Cohort Japan 20 Med (range), 70 (52–83) Med (range), 7.4 (3.54–19.9) Med (range), 38 (24–68) Biopsy naive Spinal Transperineal 12 cores 1.5 Biojet Transrectal Yes NR
Salami et al 2015 (18) Cohort USA 140 NR NR NR Negative NR TRUS 12 cores 3 UroNav Transrectal Yes 2
Mozer et al 2015 (19) Cohort France 152 Med (IQR), 63.7 (59.3–67.5) Med (IQR), 6 (5–7.9) Med (IQR), 38.5 (30–55) Biopsy naive NR TRUS 12 cores 1.5 UroStation Transrectal No 2 or 3
Volkin et al 2015 (25) Cohort USA 162 Med (range), 63 (44–80) Med (range), 8.4 (0.3–95.8) Med (range), 48 (19–187) Mixed Local TRUS 12 cores 3 NR Transrectal No ≥2
Rastinehad et al 2014 (20) Cohort USA 105 Mean (range), 65.8 (42–87) Mean (range), 9.2 (0.6–62) NR Mixed NR TRUS 12 cores 3 UroNav Transrectal Yes NR
Sonn et al 2014 (26) Cohort USA 105 Med (IQR), 65 (59–70) Med (IQR), 7.5 (5–11.2) Med (IQR), 58 (39–82) Negative Local TRUS 12 cores 3 Artemis Transrectal Yes Mean (range), 4.2 (1–9)
Wysock et al 2014 (27) Cohort USA 125 Med (range), 65 (56.3–71) Med (range), 5.1 (3.5–7.3) Med (range), 46 (31–62.5) Mixed Local TRUS 12 cores 3 Artemis Transrectal Yes 2
Fiard et al 2013 (21) Cohort France 20 Med (range), 65 (62–68) Med (range), 6.3 (5.3–10) Med (range), 39 (29–49) Mixed Local or general TRUS 12 cores 3 UroStation Transrectal No 2
Delongchamps et al 2013 (23) Cohort France 133 Mean ± SD, 64.5±7.9 Mean ± SD, 9±3.9 Mean ± SD, 58.3±28.6 Biopsy naive NR TRUS 10–12 cores 1.5 Koelis Transrectal No ≥2
Puech et al 2013 (24) Cohort France 95 Med (range), 65 (49–76) Mean ± SD, 10.05±8.8 Mean ± SD, 52±24 Mixed Local TRUS 12 cores 1.5 Virtual Navigator Transrectal No 2
Kuru et al 2013 (28) Cohort Germany 347 Med (range), 65.3 (42–82) Mean (range), 9.85 (0.5–104) Mean (range), 48.7 (9–108) Mixed General Transperineal 24 cores 3 BiopSee Transperineal Yes Med (range), 4 (2–6)
Vourganti et al 2012 (22) Cohort USA 195 Med (range), 62 (37–80) Med (range), 9.13 (0.3–103) Med (range), 56 (16–187) Negative Local TRUS 12 cores 3 NR Transrectal No Med (range), 5 (2–14)
Miyagawa et al 2010 (2) Cohort Japan 85 Med (range), 69 (56–84) Med (range), 9.9 (4.0–34.2) Med (range), 37.2 (18–141) Negative Spinal TRUS/transperineal 10–11 cores 1.5 RVS Transperineal Yes Mean, 1.9

PSA, prostate-specific antigen; MRI, magnetic resonance imaging; TRUS, transrectal ultrasound; RCT, randomized controlled trial; med, median; SD, standard deviation; IQR, interquartile range; NR, not reported.

Quality assessment of the studies included in the meta-analysis.

Overall cancer detection (n/total) Clinically significant cancer detection (n/total)
Author, year (Refs.) Main race Definition of clinically significant disease Fusion biopsy System biopsy Fusion biopsy System biopsy
Baco et al, 2015 (29) Caucasian Gleason ≥7 or maximum cancer core length ≥5 mm 51/86 48/89 33/86 44/89
Siddiqui et al, 2015 (30) Caucasian NR 461/1,003 469/1,003 – –
Borkowetz et al, 2015 (31) Caucasian Gleason >6, or >2 cores, or >50% of any core 116/263 91/263 94/263 75/263
Sankineni et al, 2015 (12) Caucasian Gleason >3+4 with 25% biopsy core involvement 24/33 19/33 16/33 13/33
Zhang et al, 2015 (13) Asian Gleason ≥3+4 or cancer core length ≥4 mm 27/62 21/62 14/62 5/62
de Gorski et al, 2015 (14) Caucasian Gleason ≥3+4 or cancer core length ≥4 mm 126/232 129/232 102/232 91/232
Ukimura et al, 2015 (15) Caucasian Gleason ≥3+4 or cancer core length ≥5 mm 78/127 52/127 54/127 29/127
Junker et al, 2015 (16) Caucasian NR 23/50 18/50 – –
Shoji et al, 2015 (17) Asian NR 14/20 8/20 – –
Salami et al, 2015 (18) Caucasian Gleason >6, or >2 cores, or >50% of any core 68/140 73/140 67/140 43/140
Mozer et al, 2015 (19) Caucasian Gleason ≥3+4 or cancer core length ≥4 mm 82/152 86/152 66/152 56/152
Volkin et al, 2014 (25) Caucasian NR 19/42 18/42 – –
Rastinehad et al, 2014 (20) Caucasian Gleason >6, or >2 cores, or >50% of any core 53/105 51/105 47/105 34/105
Sonn et al, 2014 (26) Caucasian Gleason ≥3+4 or cancer core length ≥4 mm 24/102 27/97 21/102 15/97
Wysock et al, 2014 (27) Caucasian Gleason ≥3+4 45/125 40/125 29/125 24/125
Fiard et al, 2013 (21) Caucasian Gleason ≥3+4 or total cancer length ≥10 mm 11/20 10/20 10/20 9/20
Delongchamps et al, 2013 (23) Caucasian NR 45/125 40/125 – –
Puech et al, 2013 (24) Caucasian Gleason ≥3+4 or cancer core length ≥3 mm 66/95 56/95 64/95 49/95
Kuru et al, 2013 (28) Caucasian NCCN criteria 128/253 161/253 104/253 121/253
Vourganti et al, 2012 (22) Caucasian NR 56/195 45/195 – –
Miyagawa et al, 2010 (2) Asian NR 45/85 34/85 – –
Totala 1,562/3,315 1,496/3,313 721/1,795 608/1,793

Not all studies were designed as paired cohort studies (e.g., Baco et al), resulting in the inequality of case numbers in fusion group and systematic biopsy groups. NR, not reported; NCCN, National Comprehensive Cancer Network; system, systematic.

Results of subgroup analysis of significant prostate cancer detection.

Heterogeneity Meta-analysis
Subgroups No. of studies I2 (%) P-value Effects model RR (95% CI) P-value
Study design
  Paired cohort 13 50.3 0.02 Random 1.258 (1.100–1.438) 0.001
  Comparative series   1 – – – 0.776 (0.552–1.091) 0.145
Main race
  Caucasian 13 55.2 0.008 Random 1.198 (1.047–1.370) 0.009
  Asian   1 – – – 2.800 (1.074–7.302) 0.035
Prior biopsy
  Mixed   8 59.8 0.015 Random 1.235 (1.023–1.491) 0.028
  Biopsy naive   4 62.4 0.047 Random 1.101 (0.833–1.457) 0.498
  Previous negative   2   0.0 0.645 Fixed 1.498 (1.141–1.967) 0.004
Strength of magnetic field
  3T 10 61.5 0.005 Random 1.311 (1.073–1.601) 0.008
  1.5T   4 51.6 0.102 Random 1.104 (0.914–1.333) 0.307
Sampling method
  Transrectal 12 40.3 0.072 Random 1.269 (1.104–1.459) 0.001
  Transperineal   2 81.7 0.019 Random 1.029 (0.710–1.492) 0.879

RR, relative risk; CI, confidence interval.

Results of sensitivity analysis of significant prostate cancer detection.

Heterogeneity test Pooled estimate
Sensitivity analysis I2 (%) tau2 RR (95% CI) P-value
Kuru et al (28) incorporated 56.7 0.0350 1.218 (1.060,1.399) 0.005
Kuru et al (28) excluded 34.8 0.0162 1.265 (1.119,1.429) <0.001

RR, relative risk; CI, confidence interval.