{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T12:13:06Z","timestamp":1785931986142,"version":"3.56.0"},"reference-count":18,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bjui-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJUI Compass"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study aims to validate the diagnostic accuracy of a novel urine\u2010based DNA methylation test in patients with suspected upper tract urothelial carcinoma (UTUC) on CT urography and to assess its potential to eliminate the need for diagnostic ureterorenoscopy (URS) in selected patients, expedite treatment and identify high\u2010grade tumours suitable for neoadjuvant chemotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>We prospectively collected urine samples from 46 consecutive patients with suspected UTUC in computed tomography and analysed them using the Bladder CARE\u2122 methylation test. Test performance was evaluated against final pathology from URS biopsies and\/or surgical specimens. We performed Youden Index analysis to optimise diagnostic cut\u2010off values and assessed correlations between Bladder CARE Index (BCI) levels and tumour characteristics, particularly grade differentiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Using the manufacturer's cut\u2010off (BCI\u2009&gt;\u20092.5), the test demonstrated 95% sensitivity, 69% specificity, 70% positive predictive value and 95% negative predictive value (NPV), significantly outperforming cytology (11% sensitivity). An optimised, study\u2010derived cut\u2010off (4.35) further improved specificity to 92% with sensitivity and NPV remaining \u226595%. Importantly, a higher threshold (BCI\u2009&gt;\u200910) yielded 100% specificity and 100% PPV, although at the expense of sensitivity (65%). Median BCI values differed between high\u2010grade (38.6) and low\u2010grade tumours (9.45), suggesting utility for non\u2010invasive grade assessment. BCI also correlated with tumour size (\u03b2\u2009=\u200912\u2009mm per log10 increase,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u20090.08).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This novel urine\u2010based DNA methylation test offers high diagnostic accuracy for UTUC detection. However, clinical interpretation should be threshold dependent. While BCI values &gt;2.5 show high sensitivity, the PPV of 70% indicates a relevant proportion of false\u2010positive results, and diagnostic URS remains warranted in this range. In contrast, high positive values (BCI\u2009&gt;\u200910) demonstrated 100% specificity and PPV and could enable direct progression to definitive surgery without diagnostic URS, avoiding procedure\u2010related complications and expediting treatment. The correlation with tumour grade addresses a critical need for identifying candidates for neoadjuvant chemotherapy without invasive tissue diagnosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bco2.70195","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T13:12:33Z","timestamp":1773925953000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Validation of the diagnostic accuracy of a urine\u2010based DNA methylation marker test in patients with upper urinary tract lesions"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4073-5488","authenticated-orcid":false,"given":"Christian Daniel","family":"Fankhauser","sequence":"first","affiliation":[{"name":"Faculty of Health Sciences and Medicine University of Lucerne  Lucerne Switzerland"},{"name":"Clinic for Urology University Teaching and Research Hospital of the University of Lucerne  Lucerne Switzerland"},{"name":"University of Zurich  Zurich Switzerland"},{"name":"Clinic for Urology Kantonsspital Winterthur  Winterthur Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kilian","family":"R\u00f6thlin","sequence":"additional","affiliation":[{"name":"Clinic for Urology University Teaching and Research Hospital of the University of Lucerne  Lucerne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Baumeister","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences and Medicine University of Lucerne  Lucerne Switzerland"},{"name":"Clinic for Urology University Teaching and Research Hospital of the University of Lucerne  Lucerne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5110-4796","authenticated-orcid":false,"given":"Agostino","family":"Mattei","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences and Medicine University of Lucerne  Lucerne Switzerland"},{"name":"Clinic for Urology University Teaching and Research Hospital of the University of Lucerne  Lucerne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Piatti","sequence":"additional","affiliation":[{"name":"Zymo Research Corp  Irvine California USA"},{"name":"Pangea Laboratory LLC  Tustin California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yap Ching","family":"Chew","sequence":"additional","affiliation":[{"name":"Zymo Research Corp  Irvine California USA"},{"name":"Pangea Laboratory LLC  Tustin California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8250-4634","authenticated-orcid":false,"given":"Ernest","family":"Kaufmann","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences and Medicine University of Lucerne  Lucerne Switzerland"},{"name":"Clinic for Urology 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