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Opening our eyes to multi-parametric MRI before prostate biopsyHashim U. Ahmed [1, 2], PhD, FRCS(Urol)Affiliations1. Division of Surgery, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, UK2. Imperial Urology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, UKAddress for correspondence:Hashim U. Ahmed, Professor and Chair of Urology, Room 5L28, 5th Floor, Laboratory Block, Division of Surgery and Cancer, Imperial College London, Fulham Palace Road, London, W6 8RF 7NN. E-mail: hashim.ahmed@imperial.ac.ukTel: +44 (0)20 3311 6611Key words: multi-parametric MRI, targeted biopsies, prostate cancer, PIRADS, PSA densityManuscript word count: 982There should be little doubt for the role of multi-parametric MRI (mpMRI) before a first prostate biopsy in those men who present with an elevated serum PSA. Whilst many are right to question the delivery of a high quality mpMRI across healthcare settings, such legitimate reservations about dissemination should not detract from the countless studies that now demonstrate mpMRI prior to a first [], or a second biopsy if men missed the better test first time round [], is clinically and cost-effective []. A pre-biopsy mpMRI can allow at least a quarter of men to consider avoiding an invasive test, reduces the detection of clinically insignificant prostate cancers and improves the detection of clinically significant cancers (by any definition of clinical significance one cares to use) []. In this month’s issue of European Urology, Venderink et al [] remind us that like any other radiological test, there are grey areas that make the test’s interpretation difficult. They have shown that calibrating the absolute level of PSA to the prostate’s volume can differentiate between those equivocal lesions scoring PIRADS 3 that warrant immediate biopsy and those that do not. In fact, in the current study in this issue of European Urology, we learn that using a PSA density of less than 0.12ng/ml/ml can allow a further quarter of men with equivocal scans to avoid a biopsy without missing any significant cancers. However, applying any PSA density threshold to those with PIRADS 4 or 5 lesions was not beneficial as between a quarter and one half of clinically significant prostate cancers in these men would be missed. The mpMRI score held primacy.Can this threshold be applied to men with PIRADS 1 or 2? From this study we do not know, since the group cogently argue that the false negatives from such low scores is clinically negligible and they therefore do not biopsy such men. This is a practice that many are increasingly adopting. Nonetheless, some have concerns about these missed cancers and we have to turn to another study that showed the negative predictive value of mpMRI for clinically significant prostate cancers can be improved from 92% to 98% when a PSA density of 0.15ng/ml/ml was used for mpMRI scores of 3 or less []. This compares much more favourably than the miss rate conferred by our currently applied TRUS biopsy test, in the million or so men who have a biopsy every year in Europe and another million in the USA. There should be little doubt about the triage characteristics of a high quality conducted and reported mpMRI, especially when combined with other factors such as PSA density. All centres should now be working on a clinical programme to reduce their use of TRUS biopsy.Of course, new questions start to emerge. Now that we can visualise the cancer in the majority of those that have one, what role do liquid biomarkers have []? Where exactly do these multiplex panels sit in the pathway? In the community or in secondary before mpMRI or after equivocal mpMRI results? Further, how much can we rely on existing validation studies that have been hindered by validation against TRUS-biopsy? If the histological verification test is almost no better than a toss of coin in sensitivity for detecting clinically significant cancer, it is dawning on many of us that decades of work on diagnosis and treatment, using risk stratification calculators based on a markedly inaccurate TRUS biopsy, might have less relevance now.With the recent change in the US Preventive Services Taskforce recommendations for PSA testing in the community from a ‘D’ (do not offer PSA testing) to ‘C’ (offer PSA testing following informed and shared decision making), the rates of PSA testing will likely rise again []. A community based clinical and liquid biomarker multiplex panel will be vital in acting to triage before referral into a secondary care system that might struggle to cope with mpMRI demand and capacity. Avoidance of an mpMRI might have to become the new challenge. AcknowledgementsThe author has received funding from The Wellcome Trust, NIHR-HTA, NIHR-i4i, Medical Research Council (UK), Prostate Cancer UK, Pelican Cancer Foundation and St Peters Trust. He also receives funding from Sophiris Biocorp Inc., Trod Medical and Sonacare Inc. for clinical trials. References ................
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