Variability of the Positive Predictive Value of PI-RADS for Prostate MRI across 26 Centers: Experience of the Society of Abdominal Radiology Prostate Cancer Disease-focused Panel

doi:10.1148/radiol.2020190646

Multicenter Study

. 2020 Jul;296(1):76-84.

doi: 10.1148/radiol.2020190646. Epub 2020 Apr 21.

Variability of the Positive Predictive Value of PI-RADS for Prostate MRI across 26 Centers: Experience of the Society of Abdominal Radiology Prostate Cancer Disease-focused Panel

Antonio C Westphalen¹, Charles E McCulloch¹, Jordan M Anaokar¹, Sandeep Arora¹, Nimrod S Barashi¹, Jelle O Barentsz¹, Tharakeswara K Bathala¹, Leonardo K Bittencourt¹, Michael T Booker¹, Vaughn G Braxton¹, Peter R Carroll¹, David D Casalino¹, Silvia D Chang¹, Fergus V Coakley¹, Ravjot Dhatt¹, Steven C Eberhardt¹, Bryan R Foster¹, Adam T Froemming¹, Jurgen J Fütterer¹, Dhakshina M Ganeshan¹, Mark R Gertner¹, Lori Mankowski Gettle¹, Sangeet Ghai¹, Rajan T Gupta¹, Michael E Hahn¹, Roozbeh Houshyar¹, Candice Kim¹, Chan Kyo Kim¹, Chandana Lall¹, Daniel J A Margolis¹, Stephen E McRae¹, Aytekin Oto¹, Rosaleen B Parsons¹, Nayana U Patel¹, Peter A Pinto¹, Thomas J Polascik¹, Benjamin Spilseth¹, Juliana B Starcevich¹, Varaha S Tammisetti¹, Samir S Taneja¹, Baris Turkbey¹, Sadhna Verma¹, John F Ward¹, Christopher A Warlick¹, Andrew R Weinberger¹, Jinxing Yu¹, Ronald J Zagoria¹, Andrew B Rosenkrantz¹

Affiliations

Affiliation

¹ From the Departments of Radiology and Biomedical Imaging (A.C.W., R.J.Z.), Urology (A.C.W., P.R.C.), and Epidemiology and Biostatistics (C.E.M.) and the Clinical and Translational Science Institute (C.E.M.), University of California, San Francisco, 505 Parnassus Ave, M-392, Box 0628, San Francisco, CA 94143; Department of Diagnostic Imaging, Fox Chase Cancer Center, Philadelphia, Pa (J.M.A., R.B.P.); Departments of Radiology and Radiological Sciences (S.A., V.G.B) and Urologic Surgery (S.A.), Vanderbilt University Medical Center, Nashville, Tenn; Departments of Radiology (A.O.) and Urology (N.S.B), University of Chicago, Chicago, Ill; Departments of Radiology (J.O.B) and Nuclear Medicine (J.J.F.), Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands; Departments of Diagnostic Radiology (T.K.B., D.M.G), Interventional Radiology (S.E.M.), and Urology (J.F.W.), University of Texas MD Anderson Cancer Center, Houston, Tex; Diagnósticos da América S/A, Rio de Janeiro, Brazil (L.K.B); and Department of Radiology, Fluminense Federal University of Rio de Janeiro, Rio de Janeiro, Brazil (L.K.B.); Department of Radiology, University of California, San Diego, San Diego, Calif (M.T.B., M.E.H.); UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, Calif (P.R.C.); Department of Radiology, Northwestern University, Feinberg School of Medicine, Chicago, Ill (D.D.C., A.R.W.); Department of Radiology, University of British Columbia, Vancouver, Canada (S.D.C., R.D.); Department of Diagnostic Radiology, Oregon Health Science University, Portland, Ore (F.V.C., B.R.F.); Department of Radiology, University of New Mexico Health Sciences Center, Albuquerque, NM (S.C.E., B.S., J.B.S.); and Department of Radiology, Mayo Clinic, Rochester, Minn (A.T.F.). Joint Department of Medical Imaging, University Health Network-Mount Sinai Hospital-Women's College Hospital, Toronto, Canada (M.R.G., S.G.); Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wis (L.M.G.); Departments of Radiology (R.T.G.) and Surgery (R.T.G., T.J.P.), Duke University Medical Center and Duke Cancer Institute, Durham, NC; Department of Radiological Sciences and Urology, University of California, Irvine, Orange, Calif (R.H.); Virginia Commonwealth University School of Medicine, Richmond, Va (C.K.); Department of Radiology and Center for Imaging Sciences, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (C.K.K.); Department of Radiology, University of Florida College of Medicine, Jacksonville, Fla (C.L.); Department of Radiology, Weill Cornell Medicine, New York, NY (D.J.A.M.); Department of Radiology, University of Colorado at Denver, Denver, Colo (N.U.P.); Molecular Imaging Program (B.T.) and Urologic Oncology Branch (P.A.P.), National Cancer Institute, National Institutes of Health, Bethesda, Md; Department of Diagnostic and Interventional Imaging, University of Texas Health Science Center, Houston, Tex (V.S.T.); Departments of Radiology (A.B.R.) and Urologic Oncology (S.S.T.), New York University Langone Health, New York, NY; Department of Radiology, University of Cincinnati Medical Center, Cincinnati, Ohio (S.V.); Department of Urology, University of Minnesota Institute for Prostate and Urologic Cancers, Minneapolis, Minn (C.A.W.); and Department of Radiology, Virginia Commonwealth University, Richmond, Va (J.Y.).

PMID: 32315265
PMCID: PMC7373346
DOI: 10.1148/radiol.2020190646

Multicenter Study

Variability of the Positive Predictive Value of PI-RADS for Prostate MRI across 26 Centers: Experience of the Society of Abdominal Radiology Prostate Cancer Disease-focused Panel

Antonio C Westphalen et al. Radiology. 2020 Jul.

. 2020 Jul;296(1):76-84.

doi: 10.1148/radiol.2020190646. Epub 2020 Apr 21.

Authors

Affiliation

¹ From the Departments of Radiology and Biomedical Imaging (A.C.W., R.J.Z.), Urology (A.C.W., P.R.C.), and Epidemiology and Biostatistics (C.E.M.) and the Clinical and Translational Science Institute (C.E.M.), University of California, San Francisco, 505 Parnassus Ave, M-392, Box 0628, San Francisco, CA 94143; Department of Diagnostic Imaging, Fox Chase Cancer Center, Philadelphia, Pa (J.M.A., R.B.P.); Departments of Radiology and Radiological Sciences (S.A., V.G.B) and Urologic Surgery (S.A.), Vanderbilt University Medical Center, Nashville, Tenn; Departments of Radiology (A.O.) and Urology (N.S.B), University of Chicago, Chicago, Ill; Departments of Radiology (J.O.B) and Nuclear Medicine (J.J.F.), Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands; Departments of Diagnostic Radiology (T.K.B., D.M.G), Interventional Radiology (S.E.M.), and Urology (J.F.W.), University of Texas MD Anderson Cancer Center, Houston, Tex; Diagnósticos da América S/A, Rio de Janeiro, Brazil (L.K.B); and Department of Radiology, Fluminense Federal University of Rio de Janeiro, Rio de Janeiro, Brazil (L.K.B.); Department of Radiology, University of California, San Diego, San Diego, Calif (M.T.B., M.E.H.); UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, Calif (P.R.C.); Department of Radiology, Northwestern University, Feinberg School of Medicine, Chicago, Ill (D.D.C., A.R.W.); Department of Radiology, University of British Columbia, Vancouver, Canada (S.D.C., R.D.); Department of Diagnostic Radiology, Oregon Health Science University, Portland, Ore (F.V.C., B.R.F.); Department of Radiology, University of New Mexico Health Sciences Center, Albuquerque, NM (S.C.E., B.S., J.B.S.); and Department of Radiology, Mayo Clinic, Rochester, Minn (A.T.F.). Joint Department of Medical Imaging, University Health Network-Mount Sinai Hospital-Women's College Hospital, Toronto, Canada (M.R.G., S.G.); Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wis (L.M.G.); Departments of Radiology (R.T.G.) and Surgery (R.T.G., T.J.P.), Duke University Medical Center and Duke Cancer Institute, Durham, NC; Department of Radiological Sciences and Urology, University of California, Irvine, Orange, Calif (R.H.); Virginia Commonwealth University School of Medicine, Richmond, Va (C.K.); Department of Radiology and Center for Imaging Sciences, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (C.K.K.); Department of Radiology, University of Florida College of Medicine, Jacksonville, Fla (C.L.); Department of Radiology, Weill Cornell Medicine, New York, NY (D.J.A.M.); Department of Radiology, University of Colorado at Denver, Denver, Colo (N.U.P.); Molecular Imaging Program (B.T.) and Urologic Oncology Branch (P.A.P.), National Cancer Institute, National Institutes of Health, Bethesda, Md; Department of Diagnostic and Interventional Imaging, University of Texas Health Science Center, Houston, Tex (V.S.T.); Departments of Radiology (A.B.R.) and Urologic Oncology (S.S.T.), New York University Langone Health, New York, NY; Department of Radiology, University of Cincinnati Medical Center, Cincinnati, Ohio (S.V.); Department of Urology, University of Minnesota Institute for Prostate and Urologic Cancers, Minneapolis, Minn (C.A.W.); and Department of Radiology, Virginia Commonwealth University, Richmond, Va (J.Y.).

PMID: 32315265
PMCID: PMC7373346
DOI: 10.1148/radiol.2020190646

Abstract

Background Prostate MRI is used widely in clinical care for guiding tissue sampling, active surveillance, and staging. The Prostate Imaging Reporting and Data System (PI-RADS) helps provide a standardized probabilistic approach for identifying clinically significant prostate cancer. Despite widespread use, the variability in performance of prostate MRI across practices remains unknown. Purpose To estimate the positive predictive value (PPV) of PI-RADS for the detection of high-grade prostate cancer across imaging centers. Materials and Methods This retrospective cross-sectional study was compliant with the HIPAA. Twenty-six centers with members in the Society of Abdominal Radiology Prostate Cancer Disease-focused Panel submitted data from men with suspected or biopsy-proven untreated prostate cancer. MRI scans were obtained between January 2015 and April 2018. This was followed with targeted biopsy. Only men with at least one MRI lesion assigned a PI-RADS score of 2-5 were included. Outcome was prostate cancer with Gleason score (GS) greater than or equal to 3+4 (International Society of Urological Pathology grade group ≥2). A mixed-model logistic regression with institution and individuals as random effects was used to estimate overall PPVs. The variability of observed PPV of PI-RADS across imaging centers was described by using the median and interquartile range. Results The authors evaluated 3449 men (mean age, 65 years ± 8 [standard deviation]) with 5082 lesions. Biopsy results showed 1698 cancers with GS greater than or equal to 3+4 (International Society of Urological Pathology grade group ≥2) in 2082 men. Across all centers, the estimated PPV was 35% (95% confidence interval [CI]: 27%, 43%) for a PI-RADS score greater than or equal to 3 and 49% (95% CI: 40%, 58%) for a PI-RADS score greater than or equal to 4. The interquartile ranges of PPV at these same PI-RADS score thresholds were 27%-44% and 27%-48%, respectively. Conclusion The positive predictive value of the Prostate Imaging and Reporting Data System was low and varied widely across centers. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Milot in this issue.

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Figures

**Figure 1:**
Flowchart shows the number of participating imaging centers and patients, as well as MRI and biopsy results. DFP = disease-focused panel, PI-RADS = Prostate Imaging Reporting and Data System.

Images show representative peripheral zone lesions (arrow). (a) Prostate Imaging Reporting and Data System (PI-RADS) score 2. T2-weighted MRI scan shows triangular lesion with low T2 signal intensity in right midgland. (b–d) PI-RADS score 3. T2-weighted MRI scan (b), diffusion-weighted MRI scan obtained with high b value (c), and apparent diffusion coefficient (ADC) map (d) show focal lesion in left apex. Lesion has mildly low signal intensity on ADC map and mildly high signal intensity on diffusion-weighted image. No enhancement was seen on dynamic contrast material–enhanced image (not shown). (e–g) PI-RADS score 4. T2-weighted MRI scan (e), diffusion-weighted MRI scan obtained with high b value (f), and ADC map (g) show 1.0-cm focal lesion in right midgland. Lesion has markedly low signal intensity on ADC map and markedly high signal intensity on diffusion-weighted MRI scan. (h) PI-RADS score 5. T2-weighted MRI scan shows large left midgland lesion associated with extraprostatic extension. — **Figure 2a:**
Images show representative peripheral zone lesions (arrow). **(a)** Prostate Imaging Reporting and Data System (PI-RADS) score 2. T2-weighted MRI scan shows triangular lesion with low T2 signal intensity in right midgland. **(b–d)** PI-RADS score 3. T2-weighted MRI scan (b), diffusion-weighted MRI scan obtained with high b value (c), and apparent diffusion coefficient (ADC) map (d) show focal lesion in left apex. Lesion has mildly low signal intensity on ADC map and mildly high signal intensity on diffusion-weighted image. No enhancement was seen on dynamic contrast material–enhanced image (not shown). **(e–g)** PI-RADS score 4. T2-weighted MRI scan (e), diffusion-weighted MRI scan obtained with high b value (f), and ADC map (g) show 1.0-cm focal lesion in right midgland. Lesion has markedly low signal intensity on ADC map and markedly high signal intensity on diffusion-weighted MRI scan. **(h)** PI-RADS score 5. T2-weighted MRI scan shows large left midgland lesion associated with extraprostatic extension.

T2-weighted MRI scans show representative transition zone lesions (arrow). (a) Prostate Imaging Reporting and Data System (PI-RADS) score 2. Image shows encapsulated, mildly heterogeneous nodule in left midgland to base with predominantly low signal intensity. (b) PI-RADS score 3. Image shows heterogeneous signal intensity with ill-defined margins in right midgland. (c) PI-RADS score 4. Image shows small, noncircumscribed lesion with homogeneous and moderately low signal intensity at right apex to midgland level. (d) PI-RADS score 5. Image shows bilateral midgland, large lenticular lesion in midgland with homogeneous and moderately low signal intensity that extends into the anterior fibromuscular stroma. — **Figure 3a:**
T2-weighted MRI scans show representative transition zone lesions (arrow). **(a)** Prostate Imaging Reporting and Data System (PI-RADS) score 2. Image shows encapsulated, mildly heterogeneous nodule in left midgland to base with predominantly low signal intensity. **(b)** PI-RADS score 3. Image shows heterogeneous signal intensity with ill-defined margins in right midgland. **(c)** PI-RADS score 4. Image shows small, noncircumscribed lesion with homogeneous and moderately low signal intensity at right apex to midgland level. **(d)** PI-RADS score 5. Image shows bilateral midgland, large lenticular lesion in midgland with homogeneous and moderately low signal intensity that extends into the anterior fibromuscular stroma.

Forest plots show site-specific median positive predictive values (PPVs) of (a) Prostate Imaging Reporting and Data System (PI-RADS) score greater than or equal to 3 and (b) PI-RADS score greater than or equal to 4. The overall estimated PPV for all sites is also shown. — **Figure 4a:**
Forest plots show site-specific median positive predictive values (PPVs) of **(a)** Prostate Imaging Reporting and Data System (PI-RADS) score greater than or equal to 3 and **(b)** PI-RADS score greater than or equal to 4. The overall estimated PPV for all sites is also shown.

See this image and copyright information in PMC

Comment in

Variation of PI-RADS Interpretations between Experts: A Significant Limitation.
Milot L. Milot L. Radiology. 2020 Jul;296(1):85-86. doi: 10.1148/radiol.2020192650. Epub 2020 Apr 21. Radiology. 2020. PMID: 32319860 No abstract available.
Re: Variability of the Positive Predictive Value of PI-RADS for Prostate MRI Across 26 Centers: Experience of the Society of Abdominal Radiology Prostate Cancer Disease-focused Panel.
Padhani AR, Barentsz J, Weinreb J, Schoots I, Tempany C. Padhani AR, et al. Eur Urol. 2020 Oct;78(4):633-636. doi: 10.1016/j.eururo.2020.06.015. Epub 2020 Aug 25. Eur Urol. 2020. PMID: 32859439 No abstract available.
Re: Variability of the Positive Predictive Value of PI-RADS for Prostate MRI across 26 Centers: Experience of the Society of Abdominal Radiology Prostate Cancer Disease-Focused Panel.
Taneja SS. Taneja SS. J Urol. 2020 Dec;204(6):1380-1381. doi: 10.1097/JU.0000000000001283. Epub 2020 Sep 22. J Urol. 2020. PMID: 32960704 No abstract available.
Perspectives and Concerns about PI-RADS and Variability.
Tempany-Afdhal CMC, Padhani A, Barentsz J, Weinreb J. Tempany-Afdhal CMC, et al. Radiology. 2021 Feb;298(2):E112. doi: 10.1148/radiol.2020202340. Epub 2020 Nov 24. Radiology. 2021. PMID: 33231533 No abstract available.

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References

1. Kasivisvanathan V, Rannikko AS, Borghi M, et al. . MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis. N Engl J Med 2018;378(19):1767–1777. - PMC - PubMed
1. Rosenkrantz AB, Verma S, Choyke P, et al. . Prostate Magnetic Resonance Imaging and Magnetic Resonance Imaging Targeted Biopsy in Patients with a Prior Negative Biopsy: A Consensus Statement by AUA and SAR. J Urol 2016;196(6):1613–1618. - PMC - PubMed
1. Mottet N, Bellmunt J, Briers E, et al. . EAU–ESTRO–ESUR–SIOG Guidelines on Prostate Cancer. https://uroweb.org/guideline/prostate-cancer. Published 2019. Accessed June 24, 2019. - PubMed
1. Rosenkrantz AB, Hemingway J, Hughes DR, Duszak R, Jr, Allen B, Jr, Weinreb JC. Evolving Use of Prebiopsy Prostate Magnetic Resonance Imaging in the Medicare Population. J Urol 2018;200(1):89–94. - PubMed
1. Weinreb JC, Barentsz JO, Choyke PL, et al. . PI-RADS Prostate Imaging - Reporting and Data System: 2015, Version 2. Eur Urol 2016;69(1):16–40. - PMC - PubMed

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[1] Kasivisvanathan V, Rannikko AS, Borghi M, et al. . MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis. N Engl J Med 2018;378(19):1767–1777. - PMC - PubMed

[2] Kasivisvanathan V, Rannikko AS, Borghi M, et al. . MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis. N Engl J Med 2018;378(19):1767–1777. - PMC - PubMed

[3] Rosenkrantz AB, Verma S, Choyke P, et al. . Prostate Magnetic Resonance Imaging and Magnetic Resonance Imaging Targeted Biopsy in Patients with a Prior Negative Biopsy: A Consensus Statement by AUA and SAR. J Urol 2016;196(6):1613–1618. - PMC - PubMed

[4] Rosenkrantz AB, Verma S, Choyke P, et al. . Prostate Magnetic Resonance Imaging and Magnetic Resonance Imaging Targeted Biopsy in Patients with a Prior Negative Biopsy: A Consensus Statement by AUA and SAR. J Urol 2016;196(6):1613–1618. - PMC - PubMed

[5] Mottet N, Bellmunt J, Briers E, et al. . EAU–ESTRO–ESUR–SIOG Guidelines on Prostate Cancer. https://uroweb.org/guideline/prostate-cancer. Published 2019. Accessed June 24, 2019. - PubMed

[6] Mottet N, Bellmunt J, Briers E, et al. . EAU–ESTRO–ESUR–SIOG Guidelines on Prostate Cancer. https://uroweb.org/guideline/prostate-cancer. Published 2019. Accessed June 24, 2019. - PubMed

[7] Rosenkrantz AB, Hemingway J, Hughes DR, Duszak R, Jr, Allen B, Jr, Weinreb JC. Evolving Use of Prebiopsy Prostate Magnetic Resonance Imaging in the Medicare Population. J Urol 2018;200(1):89–94. - PubMed

[8] Rosenkrantz AB, Hemingway J, Hughes DR, Duszak R, Jr, Allen B, Jr, Weinreb JC. Evolving Use of Prebiopsy Prostate Magnetic Resonance Imaging in the Medicare Population. J Urol 2018;200(1):89–94. - PubMed

[9] Weinreb JC, Barentsz JO, Choyke PL, et al. . PI-RADS Prostate Imaging - Reporting and Data System: 2015, Version 2. Eur Urol 2016;69(1):16–40. - PMC - PubMed

[10] Weinreb JC, Barentsz JO, Choyke PL, et al. . PI-RADS Prostate Imaging - Reporting and Data System: 2015, Version 2. Eur Urol 2016;69(1):16–40. - PMC - PubMed

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Variability of the Positive Predictive Value of PI-RADS for Prostate MRI across 26 Centers: Experience of the Society of Abdominal Radiology Prostate Cancer Disease-focused Panel

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Variability of the Positive Predictive Value of PI-RADS for Prostate MRI across 26 Centers: Experience of the Society of Abdominal Radiology Prostate Cancer Disease-focused Panel

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