{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T07:00:44Z","timestamp":1790406044345,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"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":["BJU International"],"abstract":"\n Objectives<\/jats:title>\n \n To evaluate how heterogeneity in response assessment protocols, including biopsy timing, complete response (CR) assessment, retreatment policies, and the handling of withdrawals, influences reported efficacy outcomes across single\u2010arm registrational trials of patients with bacillus Calmette Gu\u00e9rin unresponsive (BCG\u2010U) carcinoma\n in situ<\/jats:italic>\n (CIS).\n <\/jats:p>\n <\/jats:sec>\n \n Patients and Methods<\/jats:title>\n We reconstructed survival data from six registrational BCG\u2010U CIS trials and conducted simulation analyses to test how trial design affects efficacy estimates. Specifically, we: (i) reclassified patients who underwent re\u2010induction as non\u2010responders; (ii)\u00a0adjusted for false\u2010negative rates of cystoscopy\/cytology vs biopsy (as uniquely reported in the nadofaragene firadenovec trial, hence chosen as the analytical reference); (iii) harmonised CR assessment timing across trials. The exact binomial test was utilised for comparisons.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Re\u2010induction reclassification reduced the 12\u2010month\n CR<\/jats:styled-content>\n rate for nogapendekin alfa inbakicept (\n NAI<\/jats:styled-content>\n )\u2009+\u2009\n BCG<\/jats:styled-content>\n from 44% to 33% and for cretostimogene grenadenorepvec from 45% to 38%. After adjusting for an 11% false\u2010negative rate in trials lacking mandatory biopsies, the pembrolizumab 12\u2010month\n CR<\/jats:styled-content>\n rate declined to 17% (\n P<\/jats:italic>\n \u2009=\u20090.07), and\n NAI<\/jats:styled-content>\n , accounting for re\u2010induction reclassification, achieved a\n CR<\/jats:styled-content>\n rate of 29% (\n P<\/jats:italic>\n \u2009=\u20090.4).\n TAR<\/jats:styled-content>\n \u2010200 outperformed the analytical reference, with a 12\u2010month\n CR<\/jats:styled-content>\n rate of 45% under mandatory biopsy protocols (\n P<\/jats:italic>\n \u2009<\u20090.01).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Trial design artefacts significantly impact reported efficacy in BCG\u2010U CIS studies. Published CR rates are not directly comparable across agents. Future trials should standardise biopsy timing and clearly define retreatment policies to ensure meaningful cross\u2010study comparisons.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/bju.70463","type":"journal-article","created":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T06:50:33Z","timestamp":1790405433000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Trial design drives outcomes: harmonising efficacy across\n BCG<\/scp>\n \u2010unresponsive bladder carcinoma\n in\u00a0situ<\/i>\n trials"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6486-2169","authenticated-orcid":false,"given":"Daniele","family":"Robesti","sequence":"first","affiliation":[{"name":"Division of Experimental Oncology, Department of Urology, Urological Research Institute IRCCS Ospedale San Raffaele Milan Italy"},{"name":"Vita\u2010Salute San Raffaele University Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashish M.","family":"Kamat","sequence":"additional","affiliation":[{"name":"Department of Urology The University of Texas MD Anderson Cancer Center Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6004-2152","authenticated-orcid":false,"given":"Guillaume","family":"Ploussard","sequence":"additional","affiliation":[{"name":"Department of Urology Institut Universitaire du Cancer Toulouse\u2010Oncop\u00f4le Toulouse France"},{"name":"Department of Urology La Croix du Sud Hospital Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Contieri","sequence":"additional","affiliation":[{"name":"Department of Urology Istituto Nazionale Tumori di Napoli, IRCCS, Fondazione \u201cG. Pascale\u201d Napoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7872-2650","authenticated-orcid":false,"given":"Giuseppe","family":"Fallara","sequence":"additional","affiliation":[{"name":"Unit of Urology ASST Santi Paolo e Carlo Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Briganti","sequence":"additional","affiliation":[{"name":"Division of Experimental Oncology, Department of Urology, Urological Research Institute IRCCS Ospedale San Raffaele Milan Italy"},{"name":"Vita\u2010Salute San Raffaele University Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Montorsi","sequence":"additional","affiliation":[{"name":"Division of Experimental Oncology, Department of Urology, Urological Research Institute IRCCS Ospedale San Raffaele Milan Italy"},{"name":"Vita\u2010Salute San Raffaele University Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8839-8601","authenticated-orcid":false,"given":"Antoine G.","family":"van der Heijden","sequence":"additional","affiliation":[{"name":"Department of Urology Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2793-9459","authenticated-orcid":false,"given":"Bernard","family":"Malavaud","sequence":"additional","affiliation":[{"name":"Department of Urology Institut Universitaire du Cancer Toulouse\u2010Oncop\u00f4le Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamal","family":"Pohar","sequence":"additional","affiliation":[{"name":"Department of Urology University of Cincinnati College of Medicine Cincinnati OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5767-0548","authenticated-orcid":false,"given":"Neal","family":"Shore","sequence":"additional","affiliation":[{"name":"Department of Urology Carolina Urologic Research Center Myrtle Beach SC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8969-711X","authenticated-orcid":false,"given":"Colin P. N.","family":"Dinney","sequence":"additional","affiliation":[{"name":"Department of Urology University of Rochester Medical Center Rochester NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1272-7154","authenticated-orcid":false,"given":"Alberto","family":"Martini","sequence":"additional","affiliation":[{"name":"Department of Urology University of Cincinnati College of Medicine Cincinnati OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.euo.2020.02.006","article-title":"Evidence\u2010based assessment of current and emerging bladder\u2010sparing therapies for non\u2010muscle\u2010invasive bladder cancer after bacillus Calmette\u2010Guerin therapy: a systematic review and meta\u2010analysis","volume":"3","author":"Kamat AM","year":"2020","journal-title":"Eur 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trial designs for non\u2010muscle\u2010invasive bladder cancer: recommendations from the international bladder cancer group","volume":"34","author":"Kamat AM","year":"2016","journal-title":"J Clin Oncol"},{"key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/S1470-2045(21)00147-9","article-title":"Pembrolizumab monotherapy for the treatment of high\u2010risk non\u2010muscle\u2010invasive bladder cancer unresponsive to BCG (KEYNOTE\u2010057): an open\u2010label, single\u2010arm, multicentre, phase 2 study","volume":"22","author":"Balar AV","year":"2021","journal-title":"Lancet Oncol"},{"key":"e_1_2_10_7_1","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S1470-2045(20)30540-4","article-title":"Intravesical nadofaragene firadenovec gene therapy for BCG\u2010unresponsive non\u2010muscle\u2010invasive bladder cancer: a single\u2010arm, open\u2010label, repeat\u2010dose clinical trial","volume":"22","author":"Boorjian 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