Multicenter Study

. 2020 Aug;78(2):163-170.

doi: 10.1016/j.eururo.2020.04.029. Epub 2020 May 1.

What Type of Prostate Cancer Is Systematically Overlooked by Multiparametric Magnetic Resonance Imaging? An Analysis from the PROMIS Cohort

Joseph M Norris¹, Lina M Carmona Echeverria², Simon R J Bott³, Louise C Brown⁴, Nick Burns-Cox⁵, Tim Dudderidge⁶, Ahmed El-Shater Bosaily⁷, Eleni Frangou⁴, Alex Freeman⁸, Maneesh Ghei⁹, Alastair Henderson¹⁰, Richard G Hindley¹¹, Richard S Kaplan⁴, Alex Kirkham¹², Robert Oldroyd¹³, Chris Parker¹⁴, Raj Persad¹⁵, Shonit Punwani¹⁶, Derek J Rosario¹⁷, Iqbal S Shergill¹⁸, Vasilis Stavrinides², Mathias Winkler¹⁹, Hayley C Whitaker², Hashim U Ahmed¹⁹, Mark Emberton²⁰

Affiliations

¹ UCL Division of Surgery & Interventional Science, University College London, London, UK; London Deanery of Urology, London, UK; Department of Urology, University College London Hospitals NHS Foundation Trust, London, UK. Electronic address: joseph.norris@ucl.ac.uk.
² UCL Division of Surgery & Interventional Science, University College London, London, UK.
³ Department of Urology, Frimley Health NHS Foundation Trust, London, UK.
⁴ Medical Research Council (MRC) Clinical Trials Unit, University College London, London, UK.
⁵ Department of Urology, Taunton & Somerset NHS Foundation Trust, Taunton, UK.
⁶ Department of Urology, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
⁷ UCL Division of Surgery & Interventional Science, University College London, London, UK; Department of Radiology, Royal Free London NHS Foundation Trust, London, UK.
⁸ Department of Pathology, University College London Hospitals NHS Foundation Trust, London, UK.
⁹ Department of Urology, Whittington Health NHS Trust, London, UK.
¹⁰ Department of Urology, Maidstone & Tunbridge Wells NHS Trust, Tunbridge Wells, UK.
¹¹ Department of Urology, University College London Hospitals NHS Foundation Trust, London, UK; Department of Urology, Hampshire Hospitals NHS Foundation Trust, Hampshire, UK.
¹² Department of Radiology, University College London Hospitals NHS Foundation Trust, London, UK.
¹³ Public & Patient Representative, Nottingham, UK.
¹⁴ Department of Academic Urology, The Royal Marsden NHS Foundation Trust, Sutton, UK.
¹⁵ Department of Urology, North Bristol NHS Trust, Bristol, UK.
¹⁶ UCL Division of Surgery & Interventional Science, University College London, London, UK; Department of Radiology, University College London Hospitals NHS Foundation Trust, London, UK.
¹⁷ Department of Urology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
¹⁸ Department of Urology, Wrexham Maelor Hospital NHS Trust, Wrexham, UK.
¹⁹ Department of Urology, Imperial College Healthcare NHS Trust, London, UK; Imperial Prostate, Division of Surgery, Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, London, UK.
²⁰ UCL Division of Surgery & Interventional Science, University College London, London, UK; Department of Urology, University College London Hospitals NHS Foundation Trust, London, UK.

PMID: 32370911
PMCID: PMC7397509
DOI: 10.1016/j.eururo.2020.04.029

Multicenter Study

What Type of Prostate Cancer Is Systematically Overlooked by Multiparametric Magnetic Resonance Imaging? An Analysis from the PROMIS Cohort

Joseph M Norris et al. Eur Urol. 2020 Aug.

. 2020 Aug;78(2):163-170.

doi: 10.1016/j.eururo.2020.04.029. Epub 2020 May 1.

Authors

Affiliations

¹ UCL Division of Surgery & Interventional Science, University College London, London, UK; London Deanery of Urology, London, UK; Department of Urology, University College London Hospitals NHS Foundation Trust, London, UK. Electronic address: joseph.norris@ucl.ac.uk.
² UCL Division of Surgery & Interventional Science, University College London, London, UK.
³ Department of Urology, Frimley Health NHS Foundation Trust, London, UK.
⁴ Medical Research Council (MRC) Clinical Trials Unit, University College London, London, UK.
⁵ Department of Urology, Taunton & Somerset NHS Foundation Trust, Taunton, UK.
⁶ Department of Urology, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
⁷ UCL Division of Surgery & Interventional Science, University College London, London, UK; Department of Radiology, Royal Free London NHS Foundation Trust, London, UK.
⁸ Department of Pathology, University College London Hospitals NHS Foundation Trust, London, UK.
⁹ Department of Urology, Whittington Health NHS Trust, London, UK.
¹⁰ Department of Urology, Maidstone & Tunbridge Wells NHS Trust, Tunbridge Wells, UK.
¹¹ Department of Urology, University College London Hospitals NHS Foundation Trust, London, UK; Department of Urology, Hampshire Hospitals NHS Foundation Trust, Hampshire, UK.
¹² Department of Radiology, University College London Hospitals NHS Foundation Trust, London, UK.
¹³ Public & Patient Representative, Nottingham, UK.
¹⁴ Department of Academic Urology, The Royal Marsden NHS Foundation Trust, Sutton, UK.
¹⁵ Department of Urology, North Bristol NHS Trust, Bristol, UK.
¹⁶ UCL Division of Surgery & Interventional Science, University College London, London, UK; Department of Radiology, University College London Hospitals NHS Foundation Trust, London, UK.
¹⁷ Department of Urology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
¹⁸ Department of Urology, Wrexham Maelor Hospital NHS Trust, Wrexham, UK.
¹⁹ Department of Urology, Imperial College Healthcare NHS Trust, London, UK; Imperial Prostate, Division of Surgery, Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, London, UK.
²⁰ UCL Division of Surgery & Interventional Science, University College London, London, UK; Department of Urology, University College London Hospitals NHS Foundation Trust, London, UK.

PMID: 32370911
PMCID: PMC7397509
DOI: 10.1016/j.eururo.2020.04.029

Abstract

Background: All risk stratification strategies in cancer overlook a spectrum of disease. The Prostate MR Imaging Study (PROMIS) provides a unique opportunity to explore cancers that are overlooked by multiparametric magnetic resonance imaging (mpMRI).

Objective: To summarise attributes of cancers that are systematically overlooked by mpMRI.

Design, setting, and participants: PROMIS tested performance of mpMRI and transrectal ultrasonography (TRUS)-guided biopsy, using 5 mm template mapping (TPM) biopsy as the reference standard.

Outcome measurements and statistical analysis: Outcomes were overall and maximum Gleason scores, maximum cancer core length (MCCL), and prostate-specific antigen density (PSAD). Cancer attributes were compared between cancers that were overlooked and those that were detected.

Results and limitations: Of men with cancer, 7% (17/230; 95% confidence interval [CI] 4.4-12%) had significant disease overlooked by mpMRI according to definition 1 (Gleason ≥ 4 + 3 of any length or MCCL ≥ 6 mm of any grade) and 13% (44/331; 95% CI 9.8-17%) according to definition 2 (Gleason ≥ 3 + 4 of any length or MCCL ≥ 4 mm). In comparison, TRUS-guided biopsy overlooked 52% (119/230; 95% CI 45-58%) of significant disease by definition 1 and 40% (132/331; 95% CI 35-45%) by definition 2. Prostate cancers undetected by mpMRI had significantly lower overall and maximum Gleason scores (p = 0.0007; p < 0.0001) and shorter MCCL (median difference: 3 mm [5 vs 8 mm], p < 0.0001; 95% CI 1-3) than cancers that were detected. No tumours with overall Gleason score > 3 + 4 (Gleason Grade Groups 3-5; 95% CI 0-6.4%) or maximum Gleason score > 4 + 3 (Gleason Grade Groups 4-5; 95% CI 0-8.0%) on TPM biopsy were undetected by mpMRI. Application of a PSAD threshold of 0.15 reduced the proportion of men with undetected cancer to 5% (12/230; 95% CI 2.7-8.9%) for definition 1 and 9% (30/331; 95% CI 6.2-13%) for definition 2. Application of a PSAD threshold of 0.10 reduced the proportion of men with undetected disease to 3% (6/230; 95% CI 1.0-5.6%) for definition 1 cancer and to 3% (11/331; 95% CI 1.7-5.9%) for definition 2 cancer. Limitations were post hoc analysis and uncertain significance of undetected lesions.

Conclusions: Overall, a small proportion of cancers are overlooked by mpMRI, with estimates ranging from 4.4% (lower boundary of 95% CI for definition 1) to 17% (upper boundary of 95% CI for definition 2). Prostate cancers undetected by mpMRI are of lower grade and shorter length than cancers that are detected.

Patient summary: Prostate cancers that are undetected by magnetic resonance imaging (MRI) are smaller and less aggressive than those that are detected, and none of the most aggressive cancers are overlooked by MRI.

Keywords: False negative magnetic resonance imaging; Multiparametric magnetic resonance imaging; PROMIS; Prostate cancer; Undetected cancer.

PubMed Disclaimer

Figures

**Fig. 1**
Flow chart for study inclusion. n = sample size; mpMRI = multiparametric magnetic resonance imaging; MRI = magnetic resonance; PROMIS = Prostate Magnetic Resonance Imaging Study.

See this image and copyright information in PMC

Comment in

What Are We Missing? Magnetic Resonance Imaging-negative Clinically Significant Prostate Cancer in PROMIS.
Monda SM, Dall'Era MA. Monda SM, et al. Eur Urol. 2020 Aug;78(2):171-172. doi: 10.1016/j.eururo.2020.05.011. Epub 2020 May 22. Eur Urol. 2020. PMID: 32451182 No abstract available.

References

1. Ahmed H.U., El-Shater Bosaily A., Brown L.C. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet. 2017;389:815–822. - PubMed
1. Radtke J.P., Wiesenfarth M., Kesch C. Combined clinical parameters and multiparametric magnetic resonance imaging for advanced risk modeling of prostate cancer-patient-tailored risk stratification can reduce unnecessary biopsies. Eur Urol. 2017;72:888–896. - PubMed
1. Mehralivand S., Shih J.H., Rais-Bahrami S. A magnetic resonance imaging-based prediction model for prostate biopsy risk stratification. JAMA Oncol. 2018;4:678–685. - PMC - PubMed
1. Moldovan P.C., Van den Broeck T., Sylvester R. 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. Eur Urol. 2017;72:250–266. - PubMed
1. Kasivisvanathan V., Rannikko A.S., Borghi M. MRI-targeted or standard biopsy for prostate-cancer diagnosis. N Engl J Med. 2018;378:1767–1777. - PMC - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Medical
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

What Type of Prostate Cancer Is Systematically Overlooked by Multiparametric Magnetic Resonance Imaging? An Analysis from the PROMIS Cohort

Affiliations

What Type of Prostate Cancer Is Systematically Overlooked by Multiparametric Magnetic Resonance Imaging? An Analysis from the PROMIS Cohort

Authors

Affiliations

Abstract

Figures

Comment in

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical