Vasilis Stavrinides1, Tom Syer2, Yipeng Hu3, Francesco Giganti4, Alex Freeman5, Solon Karapanagiotis6, Simon R J Bott7, Louise C Brown8, Nicholas Burns-Cox9, Timothy J Dudderidge10, Ahmed El-Shater Bosaily11, Elena Frangou8, Maneesh Ghei12, Alastair Henderson13, Richard G Hindley14, Richard S Kaplan8, Robert Oldroyd15, Chris Parker16, Raj Persad17, Derek J Rosario18, Iqbal S Shergill19, Lina M Carmona Echeverria20, Joseph M Norris21, Mathias Winkler22, Dean Barratt3, Alex Kirkham23, Shonit Punwani24, Hayley C Whitaker20, Hashim U Ahmed22, Mark Emberton21. 1. UCL Division of Surgery & Interventional Science, University College London, London, UK; The Alan Turing Institute, London, UK; Department of Urology, University College London Hospitals NHS Foundation Trust, London, UK. Electronic address: v.stavrinides@ucl.ac.uk. 2. UCL Division of Surgery & Interventional Science, University College London, London, UK; Centre for Medical Imaging, University College London, London, UK. 3. UCL Division of Surgery & Interventional Science, University College London, London, UK; Centre for Medical Image Computing, University College London, London, UK; Wellcome EPSRC Centre for Interventional & Surgical Science (WEISS), University College London, London, UK; Department of Medical Physics & Biomedical Engineering, University College London, London, UK. 4. UCL Division of Surgery & Interventional Science, University College London, London, UK; Department of Radiology, University College London Hospitals NHS Foundation Trust, London, UK. 5. Department of Pathology, University College London Hospitals NHS Foundation Trust, London, UK. 6. The Alan Turing Institute, London, UK; Medical Research Council (MRC) Biostatistics Unit, University of Cambridge, Cambridge, UK. 7. Department of Urology, Frimley Health NHS Foundation Trust, London, UK. 8. Medical Research Council (MRC) Clinical Trials Unit, University College London, London, UK. 9. Department of Urology, Taunton & Somerset NHS Foundation Trust, Taunton, UK. 10. Department of Urology, University Hospital Southampton NHS Foundation Trust, Southampton, UK. 11. Department of Radiology, Royal Free London NHS Foundation Trust, London, UK. 12. Department of Urology, Whittington Health NHS Trust, London, UK. 13. Department of Urology, Maidstone & Tunbridge Wells NHS Trust, Tunbridge Wells, UK. 14. Department of Urology, Hampshire Hospitals NHS Foundation Trust, Hampshire, UK. 15. Public and patient representative, Nottingham, UK. 16. Department of Academic Urology, The Royal Marsden NHS Foundation Trust, Sutton, UK. 17. Department of Urology, North Bristol NHS Trust, Bristol, UK. 18. Department of Urology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK. 19. Department of Urology, Wrexham Maelor Hospital NHS Trust, Wrexham, UK. 20. UCL Division of Surgery & Interventional Science, University College London, London, UK. 21. UCL Division of Surgery & Interventional Science, University College London, London, UK; Department of Urology, University College London Hospitals NHS Foundation Trust, London, UK. 22. 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. 23. Department of Radiology, University College London Hospitals NHS Foundation Trust, London, UK. 24. UCL Division of Surgery & Interventional Science, University College London, London, UK; Centre for Medical Imaging, University College London, London, UK; Department of Radiology, University College London Hospitals NHS Foundation Trust, London, UK.
Abstract
BACKGROUND: False positive multiparametric magnetic resonance imaging (mpMRI) phenotypes prompt unnecessary biopsies. The Prostate MRI Imaging Study (PROMIS) provides a unique opportunity to explore such phenotypes in biopsy-naïve men with raised prostate-specific antigen (PSA) and suspected cancer. OBJECTIVE: To compare mpMRI lesions in men with/without significant cancer on transperineal mapping biopsy (TPM). DESIGN, SETTING, AND PARTICIPANTS: PROMIS participants (n=235) underwent mpMRI followed by a combined biopsy procedure at University College London Hospital, including 5-mm TPM as the reference standard. Patients were divided into four mutually exclusive groups according to TPM findings: (1) no cancer, (2) insignificant cancer, (3) definition 2 significant cancer (Gleason ≥3+4 of any length and/or maximum cancer core length ≥4mm of any grade), and (4) definition 1 significant cancer (Gleason ≥4+3 of any length and/or maximum cancer core length ≥6mm of any grade). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Index and/or additional lesions present in 178 participants were compared between TPM groups in terms of number, conspicuity, volume, location, and radiological characteristics. RESULTS AND LIMITATIONS: Most lesions were located in the peripheral zone. More men with significant cancer had two or more lesions than those without significant disease (67% vs 37%; p< 0.001). In the former group, index lesions were larger (mean volume 0.68 vs 0.50 ml; p< 0.001, Wilcoxon test), more conspicuous (Likert 4-5: 79% vs 22%; p< 0.001), and diffusion restricted (mean apparent diffusion coefficient [ADC]: 0.73 vs 0.86; p< 0.001, Wilcoxon test). In men with Likert 3 index lesions, log2PSA density and index lesion ADC were significant predictors of definition 1/2 disease in a logistic regression model (mean cross-validated area under the receiver-operator characteristic curve: 0.77 [95% confidence interval: 0.67-0.87]). CONCLUSIONS: Significant cancer-associated MRI lesions in biopsy-naïve men have clinical-radiological differences, with lesions seen in prostates without significant disease. MRI-calculated PSA density and ADC could predict significant cancer in those with indeterminate MRI phenotypes. PATIENT SUMMARY: Magnetic resonance imaging (MRI) lesions that mimic prostate cancer but are, in fact, benign prompt unnecessary biopsies in thousands of men with raised prostate-specific antigen. In this study we found that, on closer look, such false positive lesions have different features from cancerous ones. This means that doctors could potentially develop better tools to identify cancer on MRI and spare some patients from unnecessary biopsies.
BACKGROUND: False positive multiparametric magnetic resonance imaging (mpMRI) phenotypes prompt unnecessary biopsies. The Prostate MRI Imaging Study (PROMIS) provides a unique opportunity to explore such phenotypes in biopsy-naïve men with raised prostate-specific antigen (PSA) and suspected cancer. OBJECTIVE: To compare mpMRI lesions in men with/without significant cancer on transperineal mapping biopsy (TPM). DESIGN, SETTING, AND PARTICIPANTS: PROMIS participants (n=235) underwent mpMRI followed by a combined biopsy procedure at University College London Hospital, including 5-mm TPM as the reference standard. Patients were divided into four mutually exclusive groups according to TPM findings: (1) no cancer, (2) insignificant cancer, (3) definition 2 significant cancer (Gleason ≥3+4 of any length and/or maximum cancer core length ≥4mm of any grade), and (4) definition 1 significant cancer (Gleason ≥4+3 of any length and/or maximum cancer core length ≥6mm of any grade). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Index and/or additional lesions present in 178 participants were compared between TPM groups in terms of number, conspicuity, volume, location, and radiological characteristics. RESULTS AND LIMITATIONS: Most lesions were located in the peripheral zone. More men with significant cancer had two or more lesions than those without significant disease (67% vs 37%; p< 0.001). In the former group, index lesions were larger (mean volume 0.68 vs 0.50 ml; p< 0.001, Wilcoxon test), more conspicuous (Likert 4-5: 79% vs 22%; p< 0.001), and diffusion restricted (mean apparent diffusion coefficient [ADC]: 0.73 vs 0.86; p< 0.001, Wilcoxon test). In men with Likert 3 index lesions, log2PSA density and index lesion ADC were significant predictors of definition 1/2 disease in a logistic regression model (mean cross-validated area under the receiver-operator characteristic curve: 0.77 [95% confidence interval: 0.67-0.87]). CONCLUSIONS: Significant cancer-associated MRI lesions in biopsy-naïve men have clinical-radiological differences, with lesions seen in prostates without significant disease. MRI-calculated PSA density and ADC could predict significant cancer in those with indeterminate MRI phenotypes. PATIENT SUMMARY: Magnetic resonance imaging (MRI) lesions that mimic prostate cancer but are, in fact, benign prompt unnecessary biopsies in thousands of men with raised prostate-specific antigen. In this study we found that, on closer look, such false positive lesions have different features from cancerous ones. This means that doctors could potentially develop better tools to identify cancer on MRI and spare some patients from unnecessary biopsies.
Authors: Yi Zhao; Benjamin S Simpson; Naomi Morka; Alex Freeman; Alex Kirkham; Daniel Kelly; Hayley C Whitaker; Mark Emberton; Joseph M Norris Journal: Cancers (Basel) Date: 2022-07-19 Impact factor: 6.575