What Is the Negative Predictive Value of Multiparametric Magnetic Resonance Imaging in Excluding Prostate Cancer at Biopsy? A Systematic Review and Meta-analysis from the European Association of Urology Prostate Cancer Guidelines Panel

It remains unclear whether patients with a suspicion of prostate cancer (PCa) and negative multiparametric magnetic resonance imaging (mpMRI) can safely obviate prostate biopsy. To systematically review the literature assessing the negative predictive value (NPV) of mpMRI in patients with a suspicio...

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Published inEuropean urology Vol. 72; no. 2; pp. 250 - 266
Main Authors Moldovan, Paul C., Van den Broeck, Thomas, Sylvester, Richard, Marconi, Lorenzo, Bellmunt, Joaquim, van den Bergh, Roderick C.N., Bolla, Michel, Briers, Erik, Cumberbatch, Marcus G., Fossati, Nicola, Gross, Tobias, Henry, Ann M., Joniau, Steven, van der Kwast, Theo H., Matveev, Vsevolod B., van der Poel, Henk G., De Santis, Maria, Schoots, Ivo G., Wiegel, Thomas, Yuan, Cathy Yuhong, Cornford, Philip, Mottet, Nicolas, Lam, Thomas B., Rouvière, Olivier
Format Journal Article
LanguageEnglish
Published Switzerland Elsevier B.V 01.08.2017
Subjects
Online AccessGet full text
ISSN0302-2838
1873-7560
1421-993X
1873-7560
DOI10.1016/j.eururo.2017.02.026

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Abstract It remains unclear whether patients with a suspicion of prostate cancer (PCa) and negative multiparametric magnetic resonance imaging (mpMRI) can safely obviate prostate biopsy. To systematically review the literature assessing the negative predictive value (NPV) of mpMRI in patients with a suspicion of PCa. The Embase, Medline, and Cochrane databases were searched up to February 2016. Studies reporting prebiopsy mpMRI results using transrectal or transperineal biopsy as a reference standard were included. We further selected for meta-analysis studies with at least 10-core biopsies as the reference standard, mpMRI comprising at least T2-weighted and diffusion-weighted imaging, positive mpMRI defined as a Prostate Imaging Reporting Data System/Likert score of ≥3/5 or ≥4/5, and results reported at patient level for the detection of overall PCa or clinically significant PCa (csPCa) defined as Gleason ≥7 cancer. A total of 48 studies (9613 patients) were eligible for inclusion. At patient level, the median prevalence was 50.4% (interquartile range [IQR], 36.4–57.7%) for overall cancer and 32.9% (IQR, 28.1–37.2%) for csPCa. The median mpMRI NPV was 82.4% (IQR, 69.0–92.4%) for overall cancer and 88.1% (IQR, 85.7–92.3) for csPCa. NPV significantly decreased when cancer prevalence increased, for overall cancer (r=–0.64, p<0.0001) and csPCa (r=–0.75, p=0.032). Eight studies fulfilled the inclusion criteria for meta-analysis. Seven reported results for overall PCa. When the overall PCa prevalence increased from 30% to 60%, the combined NPV estimates decreased from 88% (95% confidence interval [95% CI], 77–99%) to 67% (95% CI, 56–79%) for a cut-off score of 3/5. Only one study selected for meta-analysis reported results for Gleason ≥7 cancers, with a positive biopsy rate of 29.3%. The corresponding NPV for a cut-off score of ≥3/5 was 87.9%. The NPV of mpMRI varied greatly depending on study design, cancer prevalence, and definitions of positive mpMRI and csPCa. As cancer prevalence was highly variable among series, risk stratification of patients should be the initial step before considering prebiopsy mpMRI and defining those in whom biopsy may be omitted when the mpMRI is negative. This systematic review examined if multiparametric magnetic resonance imaging (MRI) scan can be used to reliably predict the absence of prostate cancer in patients suspected of having prostate cancer, thereby avoiding a prostate biopsy. The results suggest that whilst it is a promising tool, it is not accurate enough to replace prostate biopsy in such patients, mainly because its accuracy is variable and influenced by the prostate cancer risk. However, its performance can be enhanced if there were more accurate ways of determining the risk of having prostate cancer. When such tools are available, it should be possible to use an MRI scan to avoid biopsy in patients at a low risk of prostate cancer. Prostate cancer prevalence was highly variable among patients referred to prebiopsy multiparametric magnetic resonance imaging (mpMRI). As the negative predictive value depends on the prevalence, patients submitted to mpMRI must be reliably risk stratified before defining who may omit prostate biopsy when mpMRI is negative.
AbstractList It remains unclear whether patients with a suspicion of prostate cancer (PCa) and negative multiparametric magnetic resonance imaging (mpMRI) can safely obviate prostate biopsy.CONTEXTIt remains unclear whether patients with a suspicion of prostate cancer (PCa) and negative multiparametric magnetic resonance imaging (mpMRI) can safely obviate prostate biopsy.To systematically review the literature assessing the negative predictive value (NPV) of mpMRI in patients with a suspicion of PCa.OBJECTIVETo systematically review the literature assessing the negative predictive value (NPV) of mpMRI in patients with a suspicion of PCa.The Embase, Medline, and Cochrane databases were searched up to February 2016. Studies reporting prebiopsy mpMRI results using transrectal or transperineal biopsy as a reference standard were included. We further selected for meta-analysis studies with at least 10-core biopsies as the reference standard, mpMRI comprising at least T2-weighted and diffusion-weighted imaging, positive mpMRI defined as a Prostate Imaging Reporting Data System/Likert score of ≥3/5 or ≥4/5, and results reported at patient level for the detection of overall PCa or clinically significant PCa (csPCa) defined as Gleason ≥7 cancer.EVIDENCE ACQUISITIONThe Embase, Medline, and Cochrane databases were searched up to February 2016. Studies reporting prebiopsy mpMRI results using transrectal or transperineal biopsy as a reference standard were included. We further selected for meta-analysis studies with at least 10-core biopsies as the reference standard, mpMRI comprising at least T2-weighted and diffusion-weighted imaging, positive mpMRI defined as a Prostate Imaging Reporting Data System/Likert score of ≥3/5 or ≥4/5, and results reported at patient level for the detection of overall PCa or clinically significant PCa (csPCa) defined as Gleason ≥7 cancer.A total of 48 studies (9613 patients) were eligible for inclusion. At patient level, the median prevalence was 50.4% (interquartile range [IQR], 36.4-57.7%) for overall cancer and 32.9% (IQR, 28.1-37.2%) for csPCa. The median mpMRI NPV was 82.4% (IQR, 69.0-92.4%) for overall cancer and 88.1% (IQR, 85.7-92.3) for csPCa. NPV significantly decreased when cancer prevalence increased, for overall cancer (r=-0.64, p<0.0001) and csPCa (r=-0.75, p=0.032). Eight studies fulfilled the inclusion criteria for meta-analysis. Seven reported results for overall PCa. When the overall PCa prevalence increased from 30% to 60%, the combined NPV estimates decreased from 88% (95% confidence interval [95% CI], 77-99%) to 67% (95% CI, 56-79%) for a cut-off score of 3/5. Only one study selected for meta-analysis reported results for Gleason ≥7 cancers, with a positive biopsy rate of 29.3%. The corresponding NPV for a cut-off score of ≥3/5 was 87.9%.EVIDENCE SYNTHESISA total of 48 studies (9613 patients) were eligible for inclusion. At patient level, the median prevalence was 50.4% (interquartile range [IQR], 36.4-57.7%) for overall cancer and 32.9% (IQR, 28.1-37.2%) for csPCa. The median mpMRI NPV was 82.4% (IQR, 69.0-92.4%) for overall cancer and 88.1% (IQR, 85.7-92.3) for csPCa. NPV significantly decreased when cancer prevalence increased, for overall cancer (r=-0.64, p<0.0001) and csPCa (r=-0.75, p=0.032). Eight studies fulfilled the inclusion criteria for meta-analysis. Seven reported results for overall PCa. When the overall PCa prevalence increased from 30% to 60%, the combined NPV estimates decreased from 88% (95% confidence interval [95% CI], 77-99%) to 67% (95% CI, 56-79%) for a cut-off score of 3/5. Only one study selected for meta-analysis reported results for Gleason ≥7 cancers, with a positive biopsy rate of 29.3%. The corresponding NPV for a cut-off score of ≥3/5 was 87.9%.The NPV of mpMRI varied greatly depending on study design, cancer prevalence, and definitions of positive mpMRI and csPCa. As cancer prevalence was highly variable among series, risk stratification of patients should be the initial step before considering prebiopsy mpMRI and defining those in whom biopsy may be omitted when the mpMRI is negative.CONCLUSIONSThe NPV of mpMRI varied greatly depending on study design, cancer prevalence, and definitions of positive mpMRI and csPCa. As cancer prevalence was highly variable among series, risk stratification of patients should be the initial step before considering prebiopsy mpMRI and defining those in whom biopsy may be omitted when the mpMRI is negative.This systematic review examined if multiparametric magnetic resonance imaging (MRI) scan can be used to reliably predict the absence of prostate cancer in patients suspected of having prostate cancer, thereby avoiding a prostate biopsy. The results suggest that whilst it is a promising tool, it is not accurate enough to replace prostate biopsy in such patients, mainly because its accuracy is variable and influenced by the prostate cancer risk. However, its performance can be enhanced if there were more accurate ways of determining the risk of having prostate cancer. When such tools are available, it should be possible to use an MRI scan to avoid biopsy in patients at a low risk of prostate cancer.PATIENT SUMMARYThis systematic review examined if multiparametric magnetic resonance imaging (MRI) scan can be used to reliably predict the absence of prostate cancer in patients suspected of having prostate cancer, thereby avoiding a prostate biopsy. The results suggest that whilst it is a promising tool, it is not accurate enough to replace prostate biopsy in such patients, mainly because its accuracy is variable and influenced by the prostate cancer risk. However, its performance can be enhanced if there were more accurate ways of determining the risk of having prostate cancer. When such tools are available, it should be possible to use an MRI scan to avoid biopsy in patients at a low risk of prostate cancer.
Abstract Context It remains unclear whether patients with a suspicion of prostate cancer (PCa) and negative multiparametric magnetic resonance imaging (mpMRI) can safely obviate prostate biopsy. Objective To systematically review the literature assessing the negative predictive value (NPV) of mpMRI in patients with a suspicion of PCa. Evidence acquisition The Embase, Medline, and Cochrane databases were searched up to February 2016. Studies reporting prebiopsy mpMRI results using transrectal or transperineal biopsy as a reference standard were included. We further selected for meta-analysis studies with at least 10-core biopsies as the reference standard, mpMRI comprising at least T2-weighted and diffusion-weighted imaging, positive mpMRI defined as a Prostate Imaging Reporting Data System/Likert score of ≥3/5 or ≥4/5, and results reported at patient level for the detection of overall PCa or clinically significant PCa (csPCa) defined as Gleason ≥7 cancer. Evidence synthesis A total of 48 studies (9613 patients) were eligible for inclusion. At patient level, the median prevalence was 50.4% (interquartile range [IQR], 36.4–57.7%) for overall cancer and 32.9% (IQR, 28.1–37.2%) for csPCa. The median mpMRI NPV was 82.4% (IQR, 69.0–92.4%) for overall cancer and 88.1% (IQR, 85.7–92.3) for csPCa. NPV significantly decreased when cancer prevalence increased, for overall cancer ( r = –0.64, p < 0.0001) and csPCa ( r = –0.75, p = 0.032). Eight studies fulfilled the inclusion criteria for meta-analysis. Seven reported results for overall PCa. When the overall PCa prevalence increased from 30% to 60%, the combined NPV estimates decreased from 88% (95% confidence interval [95% CI], 77–99%) to 67% (95% CI, 56–79%) for a cut-off score of 3/5. Only one study selected for meta-analysis reported results for Gleason ≥7 cancers, with a positive biopsy rate of 29.3%. The corresponding NPV for a cut-off score of ≥3/5 was 87.9%. Conclusions The NPV of mpMRI varied greatly depending on study design, cancer prevalence, and definitions of positive mpMRI and csPCa. As cancer prevalence was highly variable among series, risk stratification of patients should be the initial step before considering prebiopsy mpMRI and defining those in whom biopsy may be omitted when the mpMRI is negative. Patient summary This systematic review examined if multiparametric magnetic resonance imaging (MRI) scan can be used to reliably predict the absence of prostate cancer in patients suspected of having prostate cancer, thereby avoiding a prostate biopsy. The results suggest that whilst it is a promising tool, it is not accurate enough to replace prostate biopsy in such patients, mainly because its accuracy is variable and influenced by the prostate cancer risk. However, its performance can be enhanced if there were more accurate ways of determining the risk of having prostate cancer. When such tools are available, it should be possible to use an MRI scan to avoid biopsy in patients at a low risk of prostate cancer.
It remains unclear whether patients with a suspicion of prostate cancer (PCa) and negative multiparametric magnetic resonance imaging (mpMRI) can safely obviate prostate biopsy. To systematically review the literature assessing the negative predictive value (NPV) of mpMRI in patients with a suspicion of PCa. The Embase, Medline, and Cochrane databases were searched up to February 2016. Studies reporting prebiopsy mpMRI results using transrectal or transperineal biopsy as a reference standard were included. We further selected for meta-analysis studies with at least 10-core biopsies as the reference standard, mpMRI comprising at least T2-weighted and diffusion-weighted imaging, positive mpMRI defined as a Prostate Imaging Reporting Data System/Likert score of ≥3/5 or ≥4/5, and results reported at patient level for the detection of overall PCa or clinically significant PCa (csPCa) defined as Gleason ≥7 cancer. A total of 48 studies (9613 patients) were eligible for inclusion. At patient level, the median prevalence was 50.4% (interquartile range [IQR], 36.4–57.7%) for overall cancer and 32.9% (IQR, 28.1–37.2%) for csPCa. The median mpMRI NPV was 82.4% (IQR, 69.0–92.4%) for overall cancer and 88.1% (IQR, 85.7–92.3) for csPCa. NPV significantly decreased when cancer prevalence increased, for overall cancer (r=–0.64, p<0.0001) and csPCa (r=–0.75, p=0.032). Eight studies fulfilled the inclusion criteria for meta-analysis. Seven reported results for overall PCa. When the overall PCa prevalence increased from 30% to 60%, the combined NPV estimates decreased from 88% (95% confidence interval [95% CI], 77–99%) to 67% (95% CI, 56–79%) for a cut-off score of 3/5. Only one study selected for meta-analysis reported results for Gleason ≥7 cancers, with a positive biopsy rate of 29.3%. The corresponding NPV for a cut-off score of ≥3/5 was 87.9%. The NPV of mpMRI varied greatly depending on study design, cancer prevalence, and definitions of positive mpMRI and csPCa. As cancer prevalence was highly variable among series, risk stratification of patients should be the initial step before considering prebiopsy mpMRI and defining those in whom biopsy may be omitted when the mpMRI is negative. This systematic review examined if multiparametric magnetic resonance imaging (MRI) scan can be used to reliably predict the absence of prostate cancer in patients suspected of having prostate cancer, thereby avoiding a prostate biopsy. The results suggest that whilst it is a promising tool, it is not accurate enough to replace prostate biopsy in such patients, mainly because its accuracy is variable and influenced by the prostate cancer risk. However, its performance can be enhanced if there were more accurate ways of determining the risk of having prostate cancer. When such tools are available, it should be possible to use an MRI scan to avoid biopsy in patients at a low risk of prostate cancer. Prostate cancer prevalence was highly variable among patients referred to prebiopsy multiparametric magnetic resonance imaging (mpMRI). As the negative predictive value depends on the prevalence, patients submitted to mpMRI must be reliably risk stratified before defining who may omit prostate biopsy when mpMRI is negative.
It remains unclear whether patients with a suspicion of prostate cancer (PCa) and negative multiparametric magnetic resonance imaging (mpMRI) can safely obviate prostate biopsy. To systematically review the literature assessing the negative predictive value (NPV) of mpMRI in patients with a suspicion of PCa. The Embase, Medline, and Cochrane databases were searched up to February 2016. Studies reporting prebiopsy mpMRI results using transrectal or transperineal biopsy as a reference standard were included. We further selected for meta-analysis studies with at least 10-core biopsies as the reference standard, mpMRI comprising at least T2-weighted and diffusion-weighted imaging, positive mpMRI defined as a Prostate Imaging Reporting Data System/Likert score of ≥3/5 or ≥4/5, and results reported at patient level for the detection of overall PCa or clinically significant PCa (csPCa) defined as Gleason ≥7 cancer. A total of 48 studies (9613 patients) were eligible for inclusion. At patient level, the median prevalence was 50.4% (interquartile range [IQR], 36.4-57.7%) for overall cancer and 32.9% (IQR, 28.1-37.2%) for csPCa. The median mpMRI NPV was 82.4% (IQR, 69.0-92.4%) for overall cancer and 88.1% (IQR, 85.7-92.3) for csPCa. NPV significantly decreased when cancer prevalence increased, for overall cancer (r=-0.64, p<0.0001) and csPCa (r=-0.75, p=0.032). Eight studies fulfilled the inclusion criteria for meta-analysis. Seven reported results for overall PCa. When the overall PCa prevalence increased from 30% to 60%, the combined NPV estimates decreased from 88% (95% confidence interval [95% CI], 77-99%) to 67% (95% CI, 56-79%) for a cut-off score of 3/5. Only one study selected for meta-analysis reported results for Gleason ≥7 cancers, with a positive biopsy rate of 29.3%. The corresponding NPV for a cut-off score of ≥3/5 was 87.9%. The NPV of mpMRI varied greatly depending on study design, cancer prevalence, and definitions of positive mpMRI and csPCa. As cancer prevalence was highly variable among series, risk stratification of patients should be the initial step before considering prebiopsy mpMRI and defining those in whom biopsy may be omitted when the mpMRI is negative. This systematic review examined if multiparametric magnetic resonance imaging (MRI) scan can be used to reliably predict the absence of prostate cancer in patients suspected of having prostate cancer, thereby avoiding a prostate biopsy. The results suggest that whilst it is a promising tool, it is not accurate enough to replace prostate biopsy in such patients, mainly because its accuracy is variable and influenced by the prostate cancer risk. However, its performance can be enhanced if there were more accurate ways of determining the risk of having prostate cancer. When such tools are available, it should be possible to use an MRI scan to avoid biopsy in patients at a low risk of prostate cancer.
Author Fossati, Nicola
Matveev, Vsevolod B.
Henry, Ann M.
Sylvester, Richard
Yuan, Cathy Yuhong
Cumberbatch, Marcus G.
Schoots, Ivo G.
Van den Broeck, Thomas
Marconi, Lorenzo
van der Poel, Henk G.
van den Bergh, Roderick C.N.
Cornford, Philip
Bellmunt, Joaquim
De Santis, Maria
Moldovan, Paul C.
Lam, Thomas B.
Gross, Tobias
Mottet, Nicolas
Bolla, Michel
Joniau, Steven
van der Kwast, Theo H.
Wiegel, Thomas
Rouvière, Olivier
Briers, Erik
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  givenname: Paul C.
  surname: Moldovan
  fullname: Moldovan, Paul C.
  organization: Hospices Civils de Lyon, Department of Urinary and Vascular Radiology, Hôpital Edouard Herriot, Lyon, France
– sequence: 2
  givenname: Thomas
  surname: Van den Broeck
  fullname: Van den Broeck, Thomas
  organization: Department of Urology, University Hospitals Leuven, Leuven, Belgium
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  givenname: Richard
  surname: Sylvester
  fullname: Sylvester, Richard
  organization: European Association of Urology Guidelines Office, Brussels, Belgium
– sequence: 4
  givenname: Lorenzo
  surname: Marconi
  fullname: Marconi, Lorenzo
  organization: Department of Urology, Coimbra University Hospital, Coimbra, Portugal
– sequence: 5
  givenname: Joaquim
  surname: Bellmunt
  fullname: Bellmunt, Joaquim
  organization: Bladder Cancer Center, Dana-Farber Cancer Institute, Boston, MA, USA
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  givenname: Roderick C.N.
  surname: van den Bergh
  fullname: van den Bergh, Roderick C.N.
  organization: Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands
– sequence: 7
  givenname: Michel
  surname: Bolla
  fullname: Bolla, Michel
  organization: Department of Radiation Therapy, CHU Grenoble, Grenoble, France
– sequence: 8
  givenname: Erik
  surname: Briers
  fullname: Briers, Erik
  organization: Patient Advocate, Hasselt, Belgium
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  givenname: Marcus G.
  surname: Cumberbatch
  fullname: Cumberbatch, Marcus G.
  organization: Academic Urology Unit, University of Sheffield, Sheffield, UK
– sequence: 10
  givenname: Nicola
  surname: Fossati
  fullname: Fossati, Nicola
  organization: Division of Oncology/Unit of Urology, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, Milan, Italy
– sequence: 11
  givenname: Tobias
  surname: Gross
  fullname: Gross, Tobias
  organization: Department of Urology, University of Bern, Inselspital, Bern, Switzerland
– sequence: 12
  givenname: Ann M.
  surname: Henry
  fullname: Henry, Ann M.
  organization: Leeds Cancer Centre, St. James's University Hospital and University of Leeds, Leeds, UK
– sequence: 13
  givenname: Steven
  surname: Joniau
  fullname: Joniau, Steven
  organization: Department of Urology, University Hospitals Leuven, Leuven, Belgium
– sequence: 14
  givenname: Theo H.
  surname: van der Kwast
  fullname: van der Kwast, Theo H.
  organization: Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands
– sequence: 15
  givenname: Vsevolod B.
  surname: Matveev
  fullname: Matveev, Vsevolod B.
  organization: N.N. Blokhin Cancer Research Center, Moscow, Russia
– sequence: 16
  givenname: Henk G.
  surname: van der Poel
  fullname: van der Poel, Henk G.
  organization: Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands
– sequence: 17
  givenname: Maria
  surname: De Santis
  fullname: De Santis, Maria
  organization: University of Warwick, Cancer Research Centre, Coventry, UK
– sequence: 18
  givenname: Ivo G.
  surname: Schoots
  fullname: Schoots, Ivo G.
  organization: Department of Radiology & Nuclear Medicine, Erasmus MCUniversity Medical Center, Rotterdam, The Netherlands
– sequence: 19
  givenname: Thomas
  surname: Wiegel
  fullname: Wiegel, Thomas
  organization: Department of Radiation Oncology, University Hospital Ulm, Ulm, Germany
– sequence: 20
  givenname: Cathy Yuhong
  surname: Yuan
  fullname: Yuan, Cathy Yuhong
  organization: Division of Gastroenterology and Cochrane UGPD Group, Department of Medicine, Health Sciences Centre, McMaster University, Hamilton, Canada
– sequence: 21
  givenname: Philip
  surname: Cornford
  fullname: Cornford, Philip
  organization: Royal Liverpool and Broadgreen Hospitals NHS Trust, Liverpool, UK
– sequence: 22
  givenname: Nicolas
  surname: Mottet
  fullname: Mottet, Nicolas
  organization: Department of Urology, University Hospital, St. Etienne, France
– sequence: 23
  givenname: Thomas B.
  surname: Lam
  fullname: Lam, Thomas B.
  organization: Academic Urology Unit, University of Aberdeen, Aberdeen, UK
– sequence: 24
  givenname: Olivier
  surname: Rouvière
  fullname: Rouvière, Olivier
  email: Olivier.rouviere@netcourrier.com
  organization: Hospices Civils de Lyon, Department of Urinary and Vascular Radiology, Hôpital Edouard Herriot, Lyon, France
BackLink https://www.ncbi.nlm.nih.gov/pubmed/28336078$$D View this record in MEDLINE/PubMed
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Snippet It remains unclear whether patients with a suspicion of prostate cancer (PCa) and negative multiparametric magnetic resonance imaging (mpMRI) can safely...
Abstract Context It remains unclear whether patients with a suspicion of prostate cancer (PCa) and negative multiparametric magnetic resonance imaging (mpMRI)...
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SubjectTerms Biopsy
Diffusion Magnetic Resonance Imaging - standards
Europe
Humans
Male
Multiparametric magnetic resonance imaging
Neoplasm Grading
Practice Guidelines as Topic - standards
Predictive Value of Tests
Prostate biopsy
Prostate cancer
Prostatic Neoplasms - diagnostic imaging
Prostatic Neoplasms - pathology
Reproducibility of Results
Risk stratification
Societies, Medical - standards
Unnecessary Procedures
Urology
Urology - standards
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Title What Is the Negative Predictive Value of Multiparametric Magnetic Resonance Imaging in Excluding Prostate Cancer at Biopsy? A Systematic Review and Meta-analysis from the European Association of Urology Prostate Cancer Guidelines Panel
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