Prostate MRI, with or without MRI-targeted biopsy, and systematic biopsy for detecting prostate cancer

Abstract

Background: Multiparametric magnetic resonance imaging (MRI), with or without MRI-targeted biopsy, is an alternative test to systematic transrectal ultrasonography-guided biopsy in men suspected of having prostate cancer. At present, evidence on which test to use is insufficient to inform detailed evidence-based decision-making.

Objectives: To determine the diagnostic accuracy of the index tests MRI only, MRI-targeted biopsy, the MRI pathway (MRI with or without MRI-targeted biopsy) and systematic biopsy as compared to template-guided biopsy as the reference standard in detecting clinically significant prostate cancer as the target condition, defined as International Society of Urological Pathology (ISUP) grade 2 or higher. Secondary target conditions were the detection of grade 1 and grade 3 or higher-grade prostate cancer, and a potential change in the number of biopsy procedures.

Search methods: We performed a comprehensive systematic literature search up to 31 July 2018. We searched CENTRAL, MEDLINE, Embase, eight other databases and one trials register.

Selection criteria: We considered for inclusion any cross-sectional study if it investigated one or more index tests verified by the reference standard, or if it investigated the agreement between the MRI pathway and systematic biopsy, both performed in the same men. We included only studies on men who were biopsy naïve or who previously had a negative biopsy (or a mix of both). Studies involving MRI had to report on both MRI-positive and MRI-negative men. All studies had to report on the primary target condition.

Data collection and analysis: Two reviewers independently extracted data and assessed the risk of bias using the QUADAS-2 tool. To estimate test accuracy, we calculated sensitivity and specificity using the bivariate model. To estimate agreement between the MRI pathway and systematic biopsy, we synthesised detection ratios by performing random-effects meta-analyses. To estimate the proportions of participants with prostate cancer detected by only one of the index tests, we used random-effects multinomial or binary logistic regression models. For the main comparisions, we assessed the certainty of evidence using GRADE.

Main results: The test accuracy analyses included 18 studies overall.MRI compared to template-guided biopsy: Based on a pooled sensitivity of 0.91 (95% confidence interval (CI): 0.83 to 0.95; 12 studies; low certainty of evidence) and a pooled specificity of 0.37 (95% CI: 0.29 to 0.46; 12 studies; low certainty of evidence) using a baseline prevalence of 30%, MRI may result in 273 (95% CI: 249 to 285) true positives, 441 false positives (95% CI: 378 to 497), 259 true negatives (95% CI: 203 to 322) and 27 (95% CI: 15 to 51) false negatives per 1000 men. We downgraded the certainty of evidence for study limitations and inconsistency.MRI-targeted biopsy compared to template-guided biopsy: Based on a pooled sensitivity of 0.80 (95% CI: 0.69 to 0.87; 8 studies; low certainty of evidence) and a pooled specificity of 0.94 (95% CI: 0.90 to 0.97; 8 studies; low certainty of evidence) using a baseline prevalence of 30%, MRI-targeted biopsy may result in 240 (95% CI: 207 to 261) true positives, 42 (95% CI: 21 to 70) false positives, 658 (95% CI: 630 to 679) true negatives and 60 (95% CI: 39 to 93) false negatives per 1000 men. We downgraded the certainty of evidence for study limitations and inconsistency.The MRI pathway compared to template-guided biopsy: Based on a pooled sensitivity of 0.72 (95% CI: 0.60 to 0.82; 8 studies; low certainty of evidence) and a pooled specificity of 0.96 (95% CI: 0.94 to 0.98; 8 studies; low certainty of evidence) using a baseline prevalence of 30%, the MRI pathway may result in 216 (95% CI: 180 to 246) true positives, 28 (95% CI: 14 to 42) false positives, 672 (95% CI: 658 to 686) true negatives and 84 (95% CI: 54 to 120) false negatives per 1000 men. We downgraded the certainty of evidence for study limitations, inconsistency and imprecision.Systemic biopsy compared to template-guided biopsy: Based on a pooled sensitivity of 0.63 (95% CI: 0.19 to 0.93; 4 studies; low certainty of evidence) and a pooled specificity of 1.00 (95% CI: 0.91 to 1.00; 4 studies; low certainty of evidence) using a baseline prevalence of 30%, systematic biopsy may result in 189 (95% CI: 57 to 279) true positives, 0 (95% CI: 0 to 63) false positives, 700 (95% CI: 637 to 700) true negatives and 111 (95% CI: 21 to 243) false negatives per 1000 men. We downgraded the certainty of evidence for study limitations and inconsistency.Agreement analyses: In a mixed population of both biopsy-naïve and prior-negative biopsy men comparing the MRI pathway to systematic biopsy, we found a pooled detection ratio of 1.12 (95% CI: 1.02 to 1.23; 25 studies). We found pooled detection ratios of 1.44 (95% CI 1.19 to 1.75; 10 studies) in prior-negative biopsy men and 1.05 (95% CI: 0.95 to 1.16; 20 studies) in biopsy-naïve men.

Authors' conclusions: Among the diagnostic strategies considered, the MRI pathway has the most favourable diagnostic accuracy in clinically significant prostate cancer detection. Compared to systematic biopsy, it increases the number of significant cancer detected while reducing the number of insignificant cancer diagnosed. The certainty in our findings was reduced by study limitations, specifically issues surrounding selection bias, as well as inconsistency. Based on these findings, further improvement of prostate cancer diagnostic pathways should be pursued.

Conflict of interest statement

Frank‐Jan H Drost: none known

Daniel F Osses: none known

Daan Nieboer: none known

Ewout W Steyerberg reports the following relevant financial activities outside the submitted work: receives royalties from Springer for the textbook entitled Clinical Prediction Models

Chris H Bangma: none known

Monique J Roobol: none known

Ivo G Schoots reports the following relevant activities related to the submitted work: a guideline associate panel member of the EAU–ESTRO–ESUR–SIOG Guidelines on Prostate Cancer

Figures

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Clinical pathway flow diagram and study design

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Study flow chart
csPCa: clinically significant prostate cancer; MRI: magnetic resonance imaging; MRI pathway: magnetic resonance imaging with subsequent magnetic resonance imaging‐targeted biopsy; MRI‐TBx: magnetic resonance imaging‐targeted biopsy; SBx: systematic biopsy

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Diagnostic test accuracy of magnetic resonance imaging (MRI) verified by template‐guided biopsy: risk of bias and applicability concerns summary: review authors' judgements about each domain for each included study

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Diagnostic test accuracy of magnetic resonance imaging‐targeted biopsy (MRI‐TBx) in MRI‐positive men: risk of bias and applicability concerns summary: review authors' judgements about each domain for each included study

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Diagnostic test accuracy of the MRI pathway: risk of bias and applicability concerns summary: review authors' judgements about each domain for each included study

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Diagnostic test accuracy of systematic biopsy (SBx): risk of bias and applicability concerns summary: review authors' judgements about each domain for each included study

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Agreement analyses between the MRI pathway and systematic biopsy (SBx): risk of bias and applicability concerns summary: review authors' judgements about each domain for each included study

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Diagnostic test accuracy of MRI for indicating grade 2 and higher prostate cancer. Summary ROC plot of MRI verified by template‐guided biopsy. The 95% confidence region illustrates the uncertainty around the pooled summary point; the 95% prediction region illustrates the heterogeneity
 MRI: magnetic resonance imaging

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Diagnostic test accuracy of MRI‐targeted biopsy for detecting grade 2 and higher prostate cancer Summary ROC plot of MRI‐targeted biopsy (in an MRI‐positive population) verified by template‐guided biopsy. The 95% confidence region illustrates the uncertainty around the pooled summary point; the 95% prediction region illustrates the heterogeneity
 MRI: magnetic resonance imaging

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Diagnostic test accuracy of the MRI pathway for detecting grade 2 and higher prostate cancer Summary ROC plot of the MRI pathway verified by template‐guided biopsy. The 95% confidence region illustrates the uncertainty around the pooled summary point; the 95% prediction region illustrates the heterogeneity
 MRI: magnetic resonance imaging; MRI pathway: MRI with or without MRI‐targeted biopsy

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Test consequence graphic showing results that would be obtained if a hypothetical cohort of 1000 men were tested for prostate cancer using the MRI pathway.

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Diagnostic test accuracy of systematic biopsy for detecting grade 2 and higher prostate cancer Summary ROC plot of systematic biopsy verified by template‐guided biopsy

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Test consequence graphic showing results that would be obtained if a hypothetical cohort of 1000 men were tested for prostate cancer using systematic biopsy.

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Comparison of diagnostic test accuracy between MRI and the MRI pathway for detecting grade 2 and higher prostate cancer. Summary ROC plot of MRI and the MRI pathway verified by template‐guided biopsy
 G: International Society of Urological Pathology grade; MRI: magnetic resonance imaging; MRI pathway: MRI with or without MRI‐targeted biopsy

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Comparison of diagnostic test accuracy between the MRI pathway and systematic biopsy for detecting grade 2 and higher prostate cancer. Summary ROC plot of the MRI pathway versus systematic biopsy, verified by template‐guided biopsy
 G: International Society of Urological Pathology grade; MRI: magnetic resonance imaging; MRI pathway: MRI with or without MRI‐targeted biopsy; SBx: systematic biopsy

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MRI‐positivity threshold effect for indicating grade 2 and higher prostate cancer. Summary ROC plot of MRI verified by template‐guided biopsy, with different thresholds for positivity: intermediate (3/5) vs high (4/5)
 G: International Society of Urological Pathology grade; MRI: magnetic resonance imaging

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MRI‐positivity threshold effect for indicating grade 3 and higher prostate cancer. Summary ROC plot of MRI verified by template‐guided biopsy, with different thresholds for positivity: intermediate (3/5) vs high (4/5)
 G: International Society of Urological Pathology grade; MRI: magnetic resonance imaging

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Forest plots of the agreement analysis (MRI pathway vs systematic biopsy) for detecting grade 2 and higher prostate cancer

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Added value of systematic biopsy plotted against the added value of the MRI pathway per population type in the agreement analysis, for detecting grade 2 and higher prostate cancer

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Diagnostic accuracy of MRI ‐ G = 1.

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Diagnostic accuracy of MRI ‐ G ≥ 1.

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Diagnostic accuracy of MRI ‐ G ≥ 2.

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Diagnostic accuracy of MRI ‐ G ≥ 3.

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Diagnostic accuracy of MRI ‐ MRI‐positvity threshold 4/5 ‐ G = 1.

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Diagnostic accuracy of MRI ‐ MRI‐positvity threshold 4/5 ‐ G ≥ 1.

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Diagnostic accuracy of MRI ‐ MRI‐positvity threshold 4/5 ‐ G ≥ 2.

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Diagnostic accuracy of MRI ‐ MRI‐positvity threshold 4/5 ‐ G ≥ 3.

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Diagnostic accuracy of MRI ‐ Biopsy‐naïve ‐ G ≥ 1.

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Diagnostic accuracy of MRI ‐ Biopsy‐naïve ‐ G ≥ 2.

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Diagnostic accuracy of MRI ‐ Biopsy‐naïve ‐ G ≥ 3.

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Diagnostic accuracy of MRI ‐ Prior‐negative biopsy ‐ G ≥ 1.

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Diagnostic accuracy of MRI ‐ Prior‐negative biopsy ‐ G ≥ 2.

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Diagnostic accuracy of MRI ‐ Prior‐negative biopsy ‐ G ≥ 3.

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Diagnostic accuracy of MRI ‐ Sensitivity analysis with composite reference standard (template‐guided biopsy + MRI‐TBx) ‐ G ≥ 2.

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Diagnostic accuracy of TBx ‐ G = 1.

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Diagnostic accuracy of TBx ‐ G ≥ 1.

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Diagnostic accuracy of TBx ‐ G ≥ 2.

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Diagnostic accuracy of TBx ‐ G ≥ 3.

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Diagnostic accuracy of the MRI‐pathway ‐ G = 1.

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Diagnostic accuracy of the MRI‐pathway ‐ G ≥ 1.

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Diagnostic accuracy of the MRI‐pathway ‐ G ≥ 2.

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Diagnostic accuracy of the MRI‐pathway ‐ G ≥ 3.

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Diagnostic accuracy of SBx ‐ G = 1.

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Diagnostic accuracy of SBx ‐ G ≥ 1.

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Diagnostic accuracy of SBx ‐ G ≥ 2.

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Diagnostic accuracy of SBx ‐ G ≥ 3.

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MRI‐pathway vs SBx ‐ G = 1.

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MRI‐pathway vs SBx ‐ G ≥ 1.

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MRI‐pathway vs SBx ‐ G ≥ 2.

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MRI‐pathway vs SBx ‐ G ≥ 3.

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MRI‐pathway vs SBx ‐ Biopsy‐naïve ‐ G = 1.

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MRI‐pathway vs SBx ‐ Biopsy‐naïve ‐ G ≥ 1.

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MRI‐pathway vs SBx ‐ Biopsy‐naïve ‐ G ≥ 3.

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MRI‐pathway vs SBx ‐ Prior‐negative biopsy ‐ G = 1.

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MRI‐pathway vs SBx ‐ Prior‐negative biopsy ‐ G ≥ 1.

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MRI‐pathway vs SBx ‐ Prior‐negative biopsy ‐ G ≥ 2.

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MRI‐pathway vs SBx ‐ Prior‐negative biopsy ‐ G ≥ 3.

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MRI‐pathway vs SBx ‐ Positive MRI ‐ G = 1.

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MRI‐pathway vs SBx ‐ Positive MRI ‐ G ≥ 1.

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MRI‐pathway vs SBx ‐ Positive MRI ‐ G ≥ 2.

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MRI‐pathway vs SBx ‐ Positive MRI ‐ G ≥ 3.

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MRI‐pathway vs SBx ‐ Negative MRI ‐ G = 1.

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MRI‐pathway vs SBx ‐ Negative MRI ‐ G ≥ 1.

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MRI‐pathway vs SBx ‐ Negative MRI ‐ G ≥ 2.

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MRI‐pathway vs SBx ‐ Negative MRI ‐ G ≥ 3.

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MRI‐pathway vs SBx ‐ Positive MRI ‐ Biopsy‐naïve ‐ G = 1.

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MRI‐pathway vs SBx ‐ Positive MRI ‐ Biopsy‐naïve ‐ G ≥ 1.

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MRI‐pathway vs SBx ‐ Positive MRI ‐ Biopsy‐naïve ‐ G ≥ 2.

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MRI‐pathway vs. SBx ‐ Positive MRI ‐ Biopsy‐naïve ‐ G ≥ 3.

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MRI‐pathway vs SBx ‐ Negative MRI ‐ Biopsy‐naïve ‐ G = 1.

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MRI‐pathway vs SBx ‐ Negative MRI ‐ Biopsy‐naïve ‐ G ≥ 1.

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MRI‐pathway vs SBx ‐ Negative MRI ‐ Biopsy‐naïve ‐ G ≥ 2.

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MRI‐pathway vs SBx ‐ Negative MRI ‐ Biopsy‐naïve ‐ G ≥ 3.

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MRI‐pathway vs SBx ‐ Positive MRI ‐ Prior‐negative biopsy ‐ G = 1.

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MRI‐pathway vs SBx ‐ Positive MRI ‐ Prior‐negative biopsy ‐ G ≥ 1.

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MRI‐pathway vs SBx ‐ Positive MRI ‐ Prior‐negative biopsy ‐ G ≥ 2.

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MRI‐pathway vs SBx ‐ Positive MRI ‐ Prior‐negative biopsy ‐ G ≥ 3.

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MRI‐pathway vs SBx ‐ Negative MRI ‐ Prior‐negative biopsy ‐ G = 1.

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MRI‐pathway vs SBx ‐ Negative MRI ‐ Prior‐negative biopsy ‐ G ≥ 1.

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MRI‐pathway vs SBx ‐ Negative MRI ‐ Prior‐negative biopsy ‐ G ≥ 2.

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MRI‐pathway vs SBx ‐ Negative MRI ‐ Prior‐negative biopsy ‐ G ≥ 3.