Allen, C

Ball, R

Emberton, M

Freeman, A

Giganti, F

Haider, A

Kirkham, A

Moore, CM

Orczyk, C

Punwani, S

Stavrinides, V

Whitaker, H

English

UCL Discovery

Author's Accepted ManuscriptRe: Does the Visibility of Grade Group 1 Prostate Cancer on Baseline Multiparametric Magnetic Resonance Imaging Impact Clinical Outcomes?Stavrinides V, Giganti F, Punwani S, Allen C, Kirkham A, Freeman A, Ball R, Haider A, Whitaker H, Orczyk C, Emberton M,  Moore CMDOI: 10.1097/JU.0000000000001295Reference: JU-20-1604To appear in: The Journal of UrologyAccepted Date: 15 July 2020Please cite this article as: Stavrinides V, Giganti F, Punwani S, Allen C, Kirkham A, Freeman A, Ball R, Haider A, Whitaker H, Orczyk C, Emberton M,  Moore CM, Re: Does the Visibility of Grade Group 1 Prostate Cancer on Baseline Multiparametric Magnetic Resonance Imaging Impact Clinical Outcomes?, The Journal of Urology® (2019), doi: 10.1097/JU.0000000000001295.DISCLAIMER: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our subscribers we are providing this early version of the article. The paper will be copy edited and typeset, and proof will be reviewed before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers thatapply to The Journal pertain.Copyright © 2020 American Urological Association Education and Research, Inc. Unauthorized reproduction of this article is prohibited.The Journal of Urology Publish Ahead of PrintDOI: 10.1097/JU.0000000000001295    Letter to the editor  Re: Does the Visibility of Grade Group 1 Prostate Cancer on Baseline Multiparametric Magnetic Resonance Imaging Impact Clinical Outcomes? Deniffel D, Salinas E, Ientilucci M, Evans AJ, Fleshner N, Ghai S, Hamilton R, Roberts A, Toi A, van der Kwast T, Zlotta A, Finelli A, Haider MA, Perlis N. DOI: 10.1097/JU.0000000000001157  Vasilis Stavrinides1,2,3, Francesco Giganti1,4, Shonit Punwani1,4, Clare Allen4, Alex Kirkham4, Alex Freeman5, Rhys Ball5, Aiman Haider5, Hayley Whitaker1, Clement Orczyk1,2, Mark Emberton1,2, Caroline M Moore1,2.  1 Division of Surgery and Interventional Science, University College London, London, UK 2 Department of Urology, University College London Hospital NHS Foundation Trust, London, UK 3 The Alan Turing Institute, London, UK 4 Department of Radiology, University College London Hospital NHS Foundation Trust, London, UK 5 Department of Pathology, University College London Hospital NHS Foundation Trust, London, UK   Corresponding author:  Vasilis Stavrinides v.stavrinides@ucl.ac.uk Division of Surgery and Interventional Science University College London Charles Bell House 43-45 Foley Street, W1T 7TS, London UK   Word count: 492 Copyright © 2020 American Urological Association Education and Research, Inc. Unauthorized reproduction of this article is prohibited.ACCEPTED UNEDITED MANUSCRIPT We would like to congratulate Deniffel and colleagues for their excellent study, which provides further evidence that the clinical trajectory of actively surveyed, magnetic resonance imaging (MRI)-visible prostate cancer is distinct from that of non-visible disease. We could not help but noting that the first key finding of the study, i.e. that the hazard of treatment almost doubles in men with equivocal (HR 2.02; 95%CI: 1.11-3.68) or positive (HR 1.93; 95%CI: 1.21-3.09) baseline MRI, is remarkably similar to results from the University College London Hospital active surveillance (AS) cohort (Stavrinides et al., 2020):1 in separate analyses not included in our original report, the HR for treatment in men with Likert 4-5 disease was 1.93 (95% CI: 1.44-2.59) after adjusting for Gleason grade, whereas other baseline predictors such as age or prostate specific antigen were either far less important or insignificant. Interestingly, although deeming Prostate Imaging-Reporting And Data System/Likert 4-5 as visible disease is appropriate for the detection of high-grade cancer, Deniffel and colleagues report that treatment-free survival is associated with baseline MRI even when this is indeterminate.  This dependence on baseline MRI visibility persisted in the absence of upgrading on follow up biopsies, despite that the hazard of upgrading was double in men with a positive baseline MRI compared to those with a negative one (HR 2.03, 95%CI: 1.06-3.86). This implies that once a cancer has been designated as MRI-visible, its clinical fate in an imaging-based AS pathway is likely to be early treatment, without upgrading events necessarily driving this tendency. This is reminiscent of the study by Eineluoto and colleagues, where progression on serial MRI was associated with protocol-based treatment change but not necessarily with upgrading, despite that baseline MRI was associated with both (Eineluoto et al., 2017).2   Whatever the clinical course during AS, the hazard of upgrading on radical prostatectomy (RP) in the Toronto report quadrupled in those with a positive baseline MRI (HR 4.45, 95% CI: 1.19-18.37). Many authors have previously reported that MRI-conspicuous Gleason Grade Group 1 (i.e. Gleason score = 6) cancers are associated with adverse features at surgery in surveillance candidates (Zhai et al., 2018),3 but observing the same association at AS exit is a very exciting finding.   Copyright © 2020 American Urological Association Education and Research, Inc. Unauthorized reproduction of this article is prohibited.ACCEPTED UNEDITED MANUSCRIPTHowever, we should not be hasty to infer that the natural evolution of MRI lesions is the main driving force behind these results. In imaging-based AS cohorts without prescriptive monitoring protocols, ascertainment bias arising from the tendency to closely monitor visible lesions could be a factor at play. This practice is justified because the more conspicuous lesions appear to progress more over time (Ghavimi et al., 2018; Giganti et al., 2018),4,5 but we should not treat the clinical trajectory of MRI-surveyed prostate cancer and its natural history as identical. However, MRI-based pathways, on the whole, seem to improve AS candidate selection (Klotz et al., 2020),6 making it more likely that biopsy upgrades or adverse RP pathology at the end of AS reflect true oncological progression. We undoubtedly have made huge strides in the last decade, but new, well-designed studies and sophisticated methodologies for analysing longitudinal data are necessary to begin addressing these exciting questions.   Disclosures:   VS is supported by an MRC Clinical Research Training Fellowship (MR/S005897/1), the Mason Medical Research Foundation (PN: 558866) and acknowledges support from The Alan Turing Institute under the EPSRC grant EP/N510129/1, as well as previous support from EACR (EACR Travel Fellowship) and UCL (Bogue Fellowship). Francesco Giganti is funded by the UCL Graduate Research Scholarship and the Brahm PhD scholarship in memory of Chris Adams. Mark Emberton receives research support from the United Kingdom’s National Institute of Health Research (NIHR) UCLH/UCL Biomedical Research Centre. He was awarded NIHR Senior Investigator in 2013. Caroline Moore acknowledges funding from the NIHR, the MRC, CRUK, Movember, PCUK and the EAU Research Foundation.  References:  1. Stavrinides, V., Giganti, F., Trock, B., Punwani, S., Allen, C., Kirkham, A., Freeman, A., Haider, A., Ball, R., McCartan, N., Whitaker, H., Orczyk, C., Emberton, M., Moore, C.M., 2020. Five-year Outcomes of Magnetic Resonance Imaging–based Active Surveillance for Prostate Cancer: A Large Cohort Study. Eur. Urol. https://doi.org/10.1016/j.eururo.2020.03.035 Copyright © 2020 American Urological Association Education and Research, Inc. Unauthorized reproduction of this article is prohibited.ACCEPTED UNEDITED MANUSCRIPT2. Eineluoto, J.T., Järvinen, P., Kenttämies, A., Kilpeläinen, T.P., Vasarainen, H., Sandeman, K., Erickson, A., Mirtti, T., Rannikko, A., 2017. Repeat multiparametric MRI in prostate cancer patients on active surveillance. PloS One 12, e0189272. https://doi.org/10.1371/journal.pone.0189272 3. Zhai, L., Fan, Y., Meng, Y., Feng, X., Yu, W., Jin, J., 2018. The role of Prostate Imaging Reporting and Data System score in Gleason 3 + 3 active surveillance candidates enrollment: a diagnostic meta-analysis. Prostate Cancer Prostatic Dis. https://doi.org/10.1038/s41391-018-0111-4 4. Ghavimi, S., Abdi, H., Waterhouse, J., Savdie, R., Chang, S., Harris, A., Machan, L., Gleave, M., So, A., Goldenberg, L., Black, P.C., 2018. Natural history of prostatic lesions on serial multiparametric magnetic resonance imaging. Can. Urol. Assoc. J. 12. https://doi.org/10.5489/cuaj.4859 5. Giganti, F., Moore, C.M., Punwani, S., Allen, C., Emberton, M., Kirkham, A., 2018. The natural history of prostate cancer on MRI: lessons from an active surveillance cohort. Prostate Cancer Prostatic Dis. 21, 556–563. https://doi.org/10.1038/s41391-018-0058-5 6. Klotz, L., Pond, G., Loblaw, A., Sugar, L., Moussa, M., Berman, D., Van der Kwast, T., Vesprini, D., Milot, L., Kebabdjian, M., Fleshner, N., Ghai, S., Chin, J., Haider, M., 2020. Randomized Study of Systematic Biopsy Versus Magnetic Resonance Imaging and Targeted and Systematic Biopsy in Men on Active Surveillance (ASIST): 2-year Postbiopsy Follow-up. Eur. Urol. 77, 311–317. https://doi.org/10.1016/j.eururo.2019.10.007   Copyright © 2020 American Urological Association Education and Research, Inc. Unauthorized reproduction of this article is prohibited.ACCEPTED UNEDITED MANUSCRIPT

Re: Does the Visibility of Grade Group 1 Prostate Cancer on Baseline Multiparametric Magnetic Resonance Imaging Impact Clinical Outcomes?

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Re: Does the Visibility of Grade Group 1 Prostate Cancer on Baseline Multiparametric Magnetic Resonance Imaging Impact Clinical Outcomes?

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