Systematic reviews Study ID Method Patient characteristics Intervention(s) Results primary outcome Results secondary and other outcomes

Transcription

1 Uitgangsvraag 1a: Plaats van (mp)mri bij de diagnostiek van prostaatcarcinoom (primair of negatief biopt) Is (mp) MRI geïndiceerd bij de primaire diagnostiek van prostaatcarcinoom? Systematic reviews Study ID Method Patient characteristics Intervention(s) Results primary outcome Results secondary and review quality Umbehr M SR Funding/CoI: supported by grants of the Swiss National Science Foundation, no CoI Search date: 8/2008 Databases: Medline, Cochrane Library, Embase Study designs: diagnostic studies N included studies: 18 Wang P SR Funding/CoI: supported by Doctoral Foundation of Xi an Jiao Tong University, China Search date: Databases: Medline, Elsevier, Springer, OVID, CNKI, Embase Study designs: prospective observational studies N included studies: 7 Eligibility criteria: patients with either previously diagnosed or suspected prostate cancer A priori patient characteristics: o Mean age: y o PSA: ng/ml Eligibility criteria: patients with suspicion of prostate cancer A priori patient characteristics: o Mean age: y o PSA: ng/ml Combined MRI and MR spectroscopy MR spectroscopy: voxel ratio 0.75 vs Pooled sensitivity: 82% (95%CI 59-94%) Pooled specificity: 88% (95%CI 80-95%) LR+: 6.8 LR-: 0.15 Pooled weighted sensitivity: 82% (95%CI 73-89%) vs. 64% (95%CI 55-72%), p< Pooled weighted specificity: 68% (95%CI 58-76%) vs. 86% (95%CI 79-91%), p< AUC: 83.4 vs. 82.7, NS Appropriate search and quality assessment No assessment of heterogeneity Quality of included studies not taken into account 16 studies (N=581) were included in meta-analysis Only results on patients with suspected cancer are here: 7 studies, N=284 Somewhat chaotic article Quality criteria are used for inclusion, but not sufficiently mentionded Number of included patients: range 22-53

2 RCTs Study ID Method Patient characteristics Intervention(s) Results primary outcome Results secondary and Park BK RCT Funding/CoI: Supported by Clinical Research Development Program grant CRS from the Samsung Medical Center; CoI not Setting: unclear, Korea Sample size: N=85 Duration: recruitment 7/ /2009 Eligibility criteria: 37-92y, abnormal DRE or high PSA levels; no treatments for prostate cancer before biopsy A priori patient characteristics: no significant differences o Mean age: 62.0y o Median PSA: 6.1 vs. 5.6 ng/ml 3 T MRI (T2W, DWI, followed by TRUS-GB (10-12 systematic cores, targeted cores if MRI +) (N=44) vs. Immediate TRUS-GB without pre-biopsy MRI (N=41) T2W: Se: 92% Sp: 65% PPV: 52% NPV: 95% T2W+DWI: Se: 85% Sp: 81% PPV: 65% NPV: 93% T2W+DCE: Se: 77% Sp: 84% PPV: 67% NPV: 90% Cancer detection rate: 29.5% (13/44) vs. 9.8% (4/41), OR 3.9 (95%CI ) Prospective inclusion, but unclear if consecutive patients No ITT analysis Unclear allocation procedure Unclear blinding Cancer prevalence: 20% No definition of high PSA Sciarra A RCT Funding/CoI: no CoI declared Setting: single university hospital, Italy Sample size: N=180 Duration: recruitment 1/2007-1/2009 Eligibility criteria: prior negative random TRUS- GB, persistent elevated PSA (4-10 ng/ml), negative DRE; no previous hormonal, surgical, or radiation therapies for prostate diseases A priori patient 1.5 T MRI (surface phased-array and endorectal coil; T2W, with MR spectroscopy followed by TRUS-GB (10 cores + 2 targeted cores for each suspicious lesion) (N=90) T2W+DWI+DCE: Se: 69% Sp: 94% PPV: 82% NPV: 88% (as in article) 1) MRI/MRS after 1 st negative biopsy: Se: 85% Sp: 82% PPV: 79% Cancer detection rate: 48.8% (44/90) vs. 24.4% (22/90), p=0.01 Consecutive patients Unclear allocation procedure Differential verification: no targeted biopsies when negative MRI

3 characteristics: no NPV: 88% significant differences vs. AUC: 0.78 o Mean age: 63.5y o Median PSA: 6.3 vs. 6.2 ng/ml Second random TRUS-GB (10 cores) within 60d after first biopsy (N=90) MRS: Se: 92% Sp: 88% PPV: 86% NPV: 94% AUC: 0.73 MRI and MRS: Se: 93% Sp: 89% PPV: 89% NPV: 93% AUC: 0.87 (p<0.01 vs. MRI and MRS alone) Blinded evaluation of reference test; blinding of image interpretation not Region-based analysis: no 2x2 tables, so not here Reconstruction of 2x2 tables does not correspond with results provided in article 2) MRI/MRS after 2 nd negative biopsy: Se: 85% Sp: 92% PPV: 92% NPV: 85% MRS: Se: 92% Sp: 79% PPV: 83% NPV: 95% MRI and MRS: Se: 93% Sp: 90% PPV: 93%

4 NPV: 90% Diagnostische studies Study ID Method Patient characteristics Intervention(s) Results primary outcome Results secondary and Arsov C Casciani E Casciani E Cohort stated hospital (N=1), Germany Sample size: N=58 Duration: 5/2010-6/2011 Retrospective cohort hospital (N=1), Italy Sample size: N=53 Duration: not Retrospective cohort Eligibility criteria: at least 1 prior negative TRUS- GB, unsuspicious DRE, persistently increased PSA >= 4 ng/ml o Median age: 67.0y o Median PSA: 9.3 ng/ml o Prior negative TRUS- GB: range % Eligibility criteria: patients with suspected prostate cancer based on rectal exploration and/or on TRUS and/or PSA levels not 70% Eligibility criteria: increment in prostate Functional MRI, 3.0 T, standard 6-channel phased-array body coil; T2W, T1W, DWI and perfusion imaging Random TRUS-GB with additional targeted cores for patients with suspicious MRI; PSA monitoring for other patients (median follow-up 49.1 weeks) (1) 1.5 T MRI with enodrectal and pelvic T1W, T2W (2) MR spectroscopy Biopsy (28 before and 25 after MRI); RALP in 31 cases (1) 1.5 T whole-body Detection of prostate cancer (unknown results not taken into account, N=3): Se 100% Sp 84% PPV 63% NPV 100% Se: 76% Sp: 56% PPV: 80% NPV: 50% MRI + MRS: Se: 95% Sp: 81% PPV: 92% NPV: 87% No statistical difference between 2 methods: Probably prospective, but not stated patients Partial verification: 1 patient declined biopsy, results were unavailable for 2 other patients Blinding not patients; many exclusions (44/97) Blinded imaging review; unclear if pathology review was blinded Included in Umbehr 2009

5 stated MRI with endorectal p=0.227 and pelvic phasedarray All second biopsies were hospital (N=1), Italy coil; T2W, T1W negative Sample size: N=70 (2) MR spectroscopy Duration: not stated (MRS) Choi MS Cirillo S Cohort Funding/CoI: funding not stated, no CoI to declare hospital (N=1), Korea Sample size: N=154 Duration: 3/2009-6/2010 Prospective cohort Setting: unclear; Italy Sample size: N=54 Duration: 7/2004-2/2006 consistency at DRE, visible nodule in peripheral zone at TRUS, PSA > 4 ng/ml o Mean age: 68.1y o Mean PSA: 9.5 ng/ml 67% Eligibility criteria: not clearly described group 1 vs. 2 o Age: 67.2 vs. 60.1y o PSA: 14.2 vs ng/ml 84% Eligibility criteria: history of persistently elevated PSA levels (total PSA >= 4 ng/ml), at least 1 prior negative TRUS-GB; no previous hormonal, surgical or irradiation therapies 12 biopsies; if positive, laparoscopic RP (N=46); if negative, second biopsy 4-8 months later (N=24) 3.0 T MRI; T1W, T2W, DWI and ADC map Group 1 : before biopsy (N=51) Group 2 : after biopsy (N=103) TRUS-GB, random (10-12 cores) and targeted (1) 1.5 T MRI with endorectal and pelvic T2W, T1W (2) MR spectroscopy Se: 85% Sp: 50% PPV: 76% NPV: 63% LR+: 1.70 LR-: 0.30 MRI + MRS: Se: 89% Sp: 79% PPV: 89% NPV: 79% LR+: 4.28 LR-: 0.14 Group 1: (wrongly in article) Se: 86% Sp: 60% PPV: 84% NPV: 64% Group 2: Se: 92% Sp: 30% PPV: 92% NPV: 30% per-patient analysis Se: 100% Sp: 65% PPV: 57% NPV: 100% per-site analysis Se: 77% Sp: 91% PPV: 43% NPV: 98% patients Blinded image interpretation; unclear if blinded evaluation of reference standard 9/79 dropouts because of nondiagnostic MRS Included in Umbehr 2009 patients; potential selection bias based on receiving of biopsy; high cancer prevalence (no targeted biopsy if negative MRI) Blinding not Consecutive patients (no targeted biopsy if negative MRI) Blinding not

6 TRUS-GB, random o Mean age: 65.4y (10 cores) and MRS: MRS: o Mean PSA: 10.8 ng/ml targeted Se: 88% Se: 82% o 52.9% had previously Sp: 70% Sp: 91% undergone 1 TRUS-GB, PPV: 58% PPV: 46% 27.8% two, 13.0% three or more NPV: 93% NPV: 98% 32% Comet-Battle J Haffner J Cohort Setting: multicentre, Spain Sample size: N=92 Duration: not stated Cohort Funding/CoI: funding not, no CoI declared Eligibility criteria: PSA > 4 ng/ml and/or abnormal DRE, with or without lower urinary tract symptoms; no deteriorated general health, no clinical suspicion of disseminated disease (based either on PSA levels or concomitant bone symptoms), no previous diagnostic of prostate cancer or prostatitis, no treatment with finasteride and/or LHRH analogues o Mean age: 62.7y o Mean PSA: 10.4 ng/ml 27% Eligibility criteria: raised PSA levels (> 3-4 ng/ml) and/or abnormal DRE; no clinical or biological 1.5 T MRI with endorectal coil; T1W, T2W TRUS-GB (6 cores); if negative biopsy, follow-up every 6 months with PSA and re-biopsy when indicated 1.5 T MRI with pelvic T2W, T1W, DCE MRI + MRS: Se: 100% Sp: 51% (p=0.03 vs. MRI alone) PPV: 49% NPV: 100% Se 80% Sp 76% PPV 56% NPV 91% Se 83% Sp 61% MRI + MRS: Se: 86% Sp: 86% (p< vs. MRI alone) PPV: 36% NPV: 99% Included in Umbehr 2009 patients; potential selection bias based on receiving of biopsy Blinded image interpretation; unclear if blinded evaluation of reference standard Consecutive patients

7 PPV 72% hospital (N=1), France NPV 75% Sample size: N=555 Duration: 9/2005-2/2008 Ibrahiem EI Iwazawa J Prospective cohort Funding/CoI: funding not, no CoI declared hospital (N=1), Egypt Sample size: N=92 Duration: 7/2008-7/2009 Retrospective cohort Funding/CoI: funding not, no CoI declared Setting: unclear, Japan Sample size: N=178 Duration: 9/ /2009 suspicion of stage T > 3 or metastases, no claustrophobia, no previous negative biopsy, no aborted biopsy protocol due to patient intolerance o Median age: 64y o Median PSA: 6.75 ng/ml 54% Eligibility criteria: >= 40 years, aged abnormal DRE, PSA >= 4 ng/ml; no prior PSA measurements and biopsy, prostatic operations, or positive family histories of prostate cancer with previous TRUS o Mean age: 65y o Mean PSA: 26.3 ng/ml 74% Eligibility criteria: elevated PSA (> 4 ng/ml) o Mean age: 68.8y o Mean PSA: 20.5 ng/ml 40% TRUS-GB (10 systematic cores, 2 additional cores per suspicious MRI area) 1.5 T MRI with surface coil; T2W, DWI and ADC map TRUS-GB (12 systematic cores); rebiopsy after 2 weeks if negative 1st biopsy and PSA was high 1.5 T MRI; T2W, DWI, DCE (gadolinium) Transrectal prostate biopsy (10-12 systematic cores, up to 2 targeted biopsies) Se 84% Sp 58% PPV 85% NPV 56% Detection of prostate cancer, whole prostate: DWI: Se 75% (p<0.001 vs. Sp 80% PPV 52% NPV 92% (p<0.001 vs. AUC: 0.85 (p<0.001 vs. Detection of prostate cancer, central gland: DWI: Se 66% (p<0.001 vs. Sp 81% PPV 45% NPV 91% (p=0.004 vs. AUC: 0.82 (p=0.002 vs. (no targeted biopsy if negative MRI) Blinding not 34/589 patients were excluded based on exclusion criteria patients (re-biopsy in case of negative 1st biopsy) Blinded image interpretation; unclear if blinded evaluation of reference standard Consecutive patients; potential selection bias based on receiving of biopsy Probably differential verification Blinded image interpretation; unclear if blinded evaluation

8 DCE: DCE: Se 37% Se 53% Sp 86% Sp 83% PPV 38% PPV 47% NPV 86% NPV 86% AUC: 0.68 AUC: 0.75 DWI + DCE: Se 73% (p<0.001 vs. Sp 80% PPV 51% NPV 91% (p<0.001 vs. AUC: 0.85 (p<0.001 vs. DWI + DCE: Se 62% (p<0.001 vs. Sp 82% PPV 45% NPV 90% (p=0.016 vs. AUC: 0.80 (p=0.012 vs. Detection of prostate cancer, peripheral zone: of reference standard Only lesion-based analysis DWI: Se 82% (p<0.001 vs. Sp 78% PPV 57% NPV 92% AUC: 0.87 (p=0.009 vs. DCE: Se 64% Sp 80% PPV 53% NPV 86% AUC: 0.80 DWI + DCE: Se 81% (p<0.001 vs. Sp 78%

9 PPV 56% NPV 92% AUC: 0.88 (p=0.001 vs. Jeong IG Kitajima K Retrospective cohort hospital (N=1), Korea Sample size: N=88 (unilateral cancer on biopsy) Duration: not Retrospective cohort hospitals (N=2), Japan Sample size: N=53 Duration: 3/2008-1/2009 Eligibility criteria: patients with prostate cancer detected by extended pattern prostate biopsy o Mean age: 65y 72% prostate cancer in second lobe Eligibility criteria: elevated PSA levels, pelvic 3.0 T MRI, subsequent prostate biopsy o Median age: 69y o Median PSA: 11.1 ng/ml 57% 1.5 T MRI with endorectal coil and T1W, T2W, DWI Radical prostatectomy 3.0 T MRI with pelvic T1W, T2W, DWI, ADC map and DCE (gadolinium) Transperineal 20-core prostate biopsy Detection of prostate cancer in second lobe: T2W: Se: 62% Sp: 36% PPV: 71% NPV: 27% T2W + DWI: (wrongly in article) Se: 87% (p=0.003 vs. T2W) Sp: 72% (p=0.004 vs. T2W) PPV: 89% NPV: 69% T2W: protocol A Se: 61% Sp: 91% PPV: 68% NPV: 88% AUC: 0.84 T2W and DWI: protocol B Se: 76% Sp: 94% PPV: 80% NPV: 93% AUC: 0.89 Sensitivity differed significantly between protocols A and B (p=0.0054), between protocols A and C (p=0.0033), and between protocols A and D (p< ). Specificity differed significantly between protocols A and D (p=0.0051). AUC differed significantly between protocols A and B (p=0.0008) and between protocols A and D (p=0.0004). patients; potential selection bias based on receiving of biopsy Blinded image interpretation; unclear if blinded evaluation of reference standard 88/130 patients had biopsy-proven prostate cancer in one lobe and a negative biopsy in the 2nd lobe Consecutive patients; potential selection bias based on receiving of biopsy Blinded image interpretation; unclear if blinded evaluation of reference standard Only lesion-based analysis

10 T2W and DCE: protocol C Se: 77% Sp: 93% PPV: 78% NPV: 93% AUC: 0.87 Kubota Y Labanaris AP Prospective cohort hospitals (N=2), Japan Sample size: N=185 Duration: 4/2004-3/2006 Prospective cohort Funding/CoI: funding not, no CoI declared Setting: academic hospitals (N=2), Germany Sample size: N=260 Duration: Eligibility criteria: elevated PSA (4-10 ng/ml); no urinary tract infection, no acute urinary retention, no prior prostatic surgery, no re-biopsy or known prostate cancer o Mean age: 68.7y o Mean PSA: 6.55 ng/ml 34% Eligibility criteria: clinical suspicion of prostate cancer, i.e. PSA > 4 ng/ml, suspicious finding on DRE, at least 1 previous negative biopsy; age =< 75y; no cardiac pacemaker, history of pelvic surgery, inflammatory bowel disease (Crohn s disease or ulcerative colitis), 1.5 T MRI with T2W TRUS-GB (8 systematic cores) 1.0 T MRI with endorectal body T1W, T2W, DWI, DCE (gadodiamide) TRUS-GB (18 systematic cores, 3 additional targeted cores for suspicious T2W, DWI and DCE: protocol D Se: 81% Sp: 96% PPV: 85% NPV: 94% AUC: 0.90 patient-based analysis Se 79% Sp 59% PPV 49% NPV 85% Se 74% Sp 81% PPV 88% NPV 62% region-based analysis Se 64% Sp 78% PPV 43% NPV 89% Level of evidence: A2 Low risk of bias Consecutive patients Blinded image evaluation; unclear if blinded evaluation of reference test Consecutive patients (no targeted biopsies if negative MRI) Blinding not for reference standard; radiologist was blinded to patients clinical data

11 external beam radiation to sites) the pelvis, anal stricture or severe hemorrhoids interfering with endorectal receiver positioning o Median age: 67.2y (+ MRI) vs. 66.1y (- MRI) o Median PSA: 8.3 ng/ml (+ MRI) vs. 9.1 ng/ml (- MRI) o 1 prior negative TRUS- GB: 87.2%; 2: 8.1%; 3: 4.7% 54% Panebianco V Prospective cohort Funding/CoI: funding not, no CoI declared hospital (N=1), Italy Sample size: N=150 Duration: 1/2007-6/2009 Eligibility criteria: negative initial TRUS-GB, persistently elevated PSA >= 4 ng/ml; no previous hormonal treatments with LHRH analogues, surgery or radiotherapy for prostate disease and contraindications to MRI o Mean age: 61.2y o Mean PSA: 9.42 ng/ml 43% (1) 1.5 T MRI with phased-array surface coil and endorectal coil; T2W, DCE (gadobutrol) (2) MR spectroscopy TRUS-GB (10 random cores, targeted if suspicious lesion) Se: 77% Sp: 90% PPV: 84% NPV: 84% MRS: Se: 83% Sp: 92% PPV: 88% NPV: 88% MRI and MRS: (2x2 tables seem slightly incorrect!) Se: 94% Sp: 91% PPV: 88% NPV: 95% NB: 2x2 tables not exactly reconstructed Consecutive patients, recruited from 180 patients included in an RCT (Sciarra 2010) Differential verification: no targeted biopsies when negative MRI Blinded evaluation of reference test; blinding of image interpretation not AUC only presented in a figure (no numerical results): significantly better for combination of MRI

12 Portalez D Prospective cohort Setting: single centre, France Sample size: N=68 Duration: 11/2007-7/2008 Eligibility criteria: negative first TRUS-GB, negative DRE, elevated PSA o Mean age: 62.4y o Mean PSA: 9.16 ng/ml 41% (1) 1.5 T MRI with integrated endorectalpelvic coil; T2W, DWI, ADC map, DCE (gadoterate meglumine) (2) MR spectroscopy TRUS-GB (systematic and targeted) peripheral zone T2W: Se: 49% Sp: 87% PPV: 29% NPV: 94% DCE: Se: 29% Sp: 93% PPV: 33% NPV: 92% and MRS Consecutive patients Differential verification: no targeted biopsies when negative MRI Blinding not Only per-lesion analysis (N=408) DWI: Se: 39% Sp: 96% PPV: 52% NPV: 93% Puech P Retrospective cohort Setting: unclear, France Sample size: N=100 Duration: 10/2005-1/2006 Eligibility criteria: PSA >= 4 ng/ml and/or suspicious DRE not 63% 1.5 T MRI with pelvic phased array coil; T2W, DCE TRUS-GB (10-12 systematic cores, 1-2 targeted cores if suspicious lesion); in MRS: wrongly in article Se: 29% Sp: 90% PPV: 25% NPV: 92% patient-based analysis Se 100% Sp 43% PPV 75% NPV 100% patients or if selection was based on receiving of biopsies Blinded evaluation of

13 37 patients radical prostatectomy was used as reference standard Rouse P Tamada T Prospective cohort Funding/CoI: funding not, CoI in article Setting: secondary hospital, UK Sample size: N=114 Duration: 11/ /2007 Retrospective cohort Funding/CoI: supported by a Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research Setting: single centre, Japan Sample size: N=50 Duration: 1/ /2009 Eligibility criteria: PSA > 3 ng/ml or suspicious nodule on rectal examination o Mean age: 63.6y o Mean PSA: 13.4 ng/ml 60% Eligibility criteria: PSA 4-10 ng/ml o Mean age: 70y o Mean PSA: 6.84 ng/ml 70% 1.5 T MRI; T2W, DCE (gadolinium), DWI (252 regions, 42 patients) TRUS-GB (systematic and targeted cores) 1.5 T MRI; T2W, TW1, DWI and DCE (gadopentetate dimeglumine) TRUS-GB (8 systematic cores) patient-based analysis (whole prostate, all cancers) T2W, DCE and DWI: Se 79% Sp 52% PPV 71% NPV 63% LR+: 1.66 LR-: 0.39 patient-based analysis T2W: Se 60% Sp 87% PPV 91% NPV 48% DWI: Se 69% Sp 87% region-based analysis T2W and DCE (432 regions): Se 71% Sp 89% PPV 67% NPV 91% LR+: 6.38 LR-: 0.33 T2W, DCE and DWI (252 regions): Se 87% Sp 87% PPV 77% NPV 93% LR+: 6.53 LR-: 0.15 region-based analysis T2W: Se 36% Sp 97% PPV 82% NPV 81% DWI: Se 38% Sp 96% images; unclear if blinded evaluation of reference standard 2x2 tables for lesionbased analysis could not be reconstructed Consecutive patients Blinded evaluation of images; unclear if blinded evaluation of reference standard patients or if selection was based on receiving of biopsies Blinded evaluation of images; unclear if blinded evaluation of reference standard

14 PPV 92% PPV 78% NPV 54% NPV 82% DCE: Se 74% Sp 80% PPV 90% NPV 57% DCE: Se 43% Sp 95% PPV 75% NPV 83% Tanimoto Prospective cohort Setting: single university centre, Japan Sample size: N=83 Duration: 1/2005-5/2005 Eligibility criteria: patients with elevated PSA (>4 ng/ml) who had both undergone an MRI and a subsequent systematic TRUS-GB o Mean age: 67.4y o Mean PSA: 19.4 ng/ml 53% 1.5 T MRI; T2W, T1W, DWI, DCE (gadolinium) TRUS-GB (systematic) T2W, DCE and DWI: Se 83% (p=0.008 vs. T2W) Sp 80% PPV 91% NPV 67% patient-based analysis T2W: Se: 73% Sp: 54% PPV: 64% NPV: 64% AUC: 0.71 TW2+DWI: Se: 84% Sp: 85% (p=0.014 vs. T2W) PPV: 86% NPV: 83% AUC: 0.91 (p=0.011 vs. T2W) T2W, DCE and DWI: Se 53% (p<0.001 vs. T2W, DCE and DWI individually) Sp 93% PPV 73% NPV 85% Consecutive patients, unclear if selection was based on receiving of reference test Blinding not T2W+DWI+DCE: Se: 95% (p=0.014 vs. T2W)

15 Sp: 74% PPV: 81% NPV: 94% AUC: 0.97 (p= vs. T2W) Testa C patient-based analysis peripheral zone Cohort hospital (N=1), Italy Sample size: N=54 Duration: 2/2007-7/2007 Eligibility criteria: persistently elevated PSA level (PSA > 4 ng/ml) and/or a positive DRE; one extended TRUSbiopsy negative for cancer performed between 6 (to avoid post-hemorrhage artefacts) and 12 months before; or two or more extended negative TRUSbiopsies with the last one taken within the 6 24 months before; interval between MRI/MRSI and the following TRUSbiopsy <3 months; no previous diagnosis of prostate cancer; treatment with 5-alpha-reductase inhibitors or anti-androgen therapy o Mean age: 63.9y o Mean PSA: 11.4 ng/ml 41% (1) 1.5 T MRI with endorectal and pelvic T2W (2) MR spectroscopy MRI/MRS-directed biopsy (targeted and systematic) Se: 73% Sp: 63% PPV: 57% NPV: 77% AUC: 0.68 MRS: Se: 91% Sp: 44% PPV: 53% NPV: 88% AUC: 0.67 MRI and MRS: Se: 73% Sp: 72% PPV: 64% NPV: 79% AUC 0.72 Se: 27% Sp: 96% PPV: 32% NPV: 95% AUC: 0.61 MRS: Se: 65% Sp: 86% PPV: 26% NPV: 97% AUC: 0.75 MRI and MRS: Se: 22% Sp: 99% PPV: 53% NPV: 95% AUC: 0.60 transition zone Se: 61% Sp: 99% PPV: 92% NPV: 93% Probably prospective inclusion, but unclear if consecutive patients Blinded evaluation of reference test, but blinding of imaging not 4/58 patients were excluded due to poor quality of MRS spectra

16 AUC: 0.80 Vilanova Retrospective Funding/CoI: supported by the Spanish Radiologic Society, the Spanish Ministry of Science, and the Agència de Gestió d Ajuts Universitaris i de Recerca of the Generalitat de Catalunya; CoI not Setting: unclear, Spain Sample size: N=70 Duration: 5/2008-9/2009 Eligibility criteria: patients who were referred for endorectal MRI, no previous prostate biopsy, PSA > 4 ng/ml, free-tototal PSA ratio < 20%; no poor general health contraindicating biopsy or prostatectomy or both, previous diagnosis of acute prostatitis, history of prostate cancer, and contraindications to MRI o Mean age: 63.5y o Median PSA: 7.4 ng/ml o Median Gleason: 7 54% (1) 1.5 T MRI with endorectal and pelvic T1W, T2W, DWI, DCE (2) MRS TRUS-GB (systematic + targeted) (N=57) or prostatectomy (N=13) patient-based analysis DWI: Se: 82% Sp: 78% PPV: 82% NPV: 78% T2W+DWI: Se: 82% Sp: 78% PPV: 82% NPV: 78% T2W-DWI and MRS: Se: 79% Sp: 81% PPV: 83% NPV: 77% MRS: Se: 72% Sp: 93% PPV: 68% NPV: 94% AUC: 0.83 MRI and MRS: Se: 61% Sp: 100% PPV: 100% NPV: 93% AUC: 0.81 region-based analysis (hemiprostate) T2W+DWI+DCE: Se: 73% Sp: 91% PPV: 82% NPV: 85% Abbreviations: 95%CI: 95% confidence interval; ADC: apparent diffusion coefficient; AUC: area under the curve; CoI: conflict of interest; DCE: dynamic contrast-enhanced; DRE: digital rectal examination; DWI: diffusion-weighted imaging; ITT: intention to treat; LR+: positive likelihood ratio; patients or if inclusion was based on receiving of tests Blinded image review, unclear if pathology review was blinded

17 LR-: negative likelihood ratio; magnetic resonance imaging; MRS: magnetic resonance spectroscopy; NPV: negative predictive value; NS: not significant; OR: odds ratio; PPV: positive predictive value; PSA: prostate-specific antigen; RALP: robotic-assisted laparoscopic prostatectomy; RCT: randomized controlled trial; RP: radical prostatectomy; Se: sensitivity; Sp: specificity; SR: systematic review; T: tesla; T1W: T1-weighted; T2W: T2- weighted; TRUS-GB: transrectal ultrasound-guided biopsy.