{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T14:55:40Z","timestamp":1768402540535,"version":"3.49.0"},"reference-count":71,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,1,22]],"date-time":"2019-01-22T00:00:00Z","timestamp":1548115200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bjui-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJU International"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This narrative review describes current guidelines for treating NMIBC, provides an overview of the principle behind immune checkpoint inhibition, and summarizes current evidence for checkpoint inhibitors in urothelial malignancy. Further, we discuss potential strategies for immune checkpoint inhibition in the management of NMIBC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Adjuvant intravesical BCG immunotherapy has been the mainstay of treatment for high\u2010risk non\u2010muscle\u2010invasive bladder cancer (NMIBC) for decades but is associated with both a significant side effect profile and failure rate. Recently, a substantial body of trial data has been published demonstrating the successful use of systemic immunotherapy in the treatment of advanced urothelial malignancy and, in particular, a class of drugs known as \u2018immune checkpoint inhibitors\u2019. This has led to the approval of a number of these drugs by the UK National Institute of Health and Care Excellence and the US Food and Drug Administration, and ongoing trials are examining use in the management of NMIBC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To identify relevant published data, using the PubMed\/ Medline search engine, an online search of the Pubmed\/ Medline archives was conducted using the terms bladder cancer' in combination with \u2018checkpoint inhibitors\u2019, and limited to articles in English published between 1966 and September 2017.To identify ongoing trials of interest but not yet published, a further search of the clinical trials.gov search engine was conducted using the term \u2018non\u2010muscle\u2010invasive bladder cancer\u2019.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>There has been little advance in available adjuvant therapy for NMIBC treated with TURBT. Current intravesical therapies are associated with a high recurrence rate and significant side effect profile. The impending publication of the wealth of ongoing trials, both into the delivery and efficacy of checkpoint inhibition will direct the future treatment of NMIBC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bju.14643","type":"journal-article","created":{"date-parts":[[2018,12,8]],"date-time":"2018-12-08T01:14:41Z","timestamp":1544231681000},"page":"947-958","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Urothelial cancer: a narrative review of the role of novel immunotherapeutic agents with particular reference to the management of non\u2010muscle\u2010invasive disease"],"prefix":"10.1111","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8978-2966","authenticated-orcid":false,"given":"Emma","family":"Doyle","sequence":"first","affiliation":[{"name":"Department of Oncology Oxford Cancer and Haematology Centre Oxford University Hospitals NHS Foundation Trust Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy","family":"Crew","sequence":"additional","affiliation":[{"name":"Department of Urology Oxford Cancer and Haematology Centre Oxford University Hospitals NHS Foundation Trust Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugh","family":"Mostafid","sequence":"additional","affiliation":[{"name":"Department of Urology Royal Surrey County Hospital Foundation Trust Guildford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Tuthill","sequence":"additional","affiliation":[{"name":"Department of Oncology Oxford Cancer and Haematology Centre Oxford University Hospitals NHS Foundation Trust Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Cerundolo","sequence":"additional","affiliation":[{"name":"MRC Human Immunology Unit Radcliffe Department of Medicine Weatherall Institute of Molecular Medicine Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Winald","family":"Gerristen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Radboud University Medical Centre Nijmegan The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Protheroe","sequence":"additional","affiliation":[{"name":"Department of Oncology Oxford Cancer and Haematology Centre Oxford University Hospitals NHS Foundation Trust Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,1,22]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"Cancer Research UK.Bladder cancer statistics. Available at:http:\/\/www.cancerresearchuk.org\/health-professional\/cancer-statistics\/statistics-by-cancer-type\/bladder-cancer. Accessed June 2017."},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2012.07.033"},{"key":"e_1_2_8_4_1","first-page":"1","article-title":"Prognostic Performance and reproducibility of the 1973 and 2004\/2016 World Health Organisation Grading Classification Systems in Non\u2010muscle\u2010invasive Bladder Cancer: a European Association of Urology Non Muscle invasive bladder cancer guidelines panel systematic review","volume":"7346","author":"Soukup V","year":"2017","journal-title":"Eur Urol"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2016.05.041"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eursup.2008.07.009"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2011.07.076"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2012.08.061"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2016.06.049"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bju.13102"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2005.12.031"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijcp.12075"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3233\/BLC-150034"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2007.08.122"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)58737-6"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2008.11.124"},{"key":"e_1_2_8_17_1","first-page":"137","article-title":"Pre\u2010existing BCG\u2010specific T cells improve intravesical immunotherapy for bladder cancer","volume":"4","author":"Biot C","year":"2012","journal-title":"Sci Transi Med"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)64273-5"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2006.01.017"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)64043-8"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.3233\/BLC-150015"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3233\/BLC-159002"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.3233\/BLC-160053"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)07422-4"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-017-0271-0"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2010.07.537"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euf.2017.06.004"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2014.01.001"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.39.2936"},{"key":"e_1_2_8_30_1","first-page":"115","article-title":"Intravesical prevention of recurrence of superficial urinary bladder cancer with BCG and KLH: a prospective randomised study","volume":"30","author":"Kalbe T","year":"1991","journal-title":"Urologe"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2017.07.024"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1514296"},{"key":"e_1_2_8_33_1","first-page":"793","article-title":"Tumor\u2010associated B7\u2010H1 promotes T cell apoptosis: a potential mechanism of immune invasion","volume":"9","author":"Dong H","year":"2012","journal-title":"Nat Med"},{"key":"e_1_2_8_34_1","doi-asserted-by":"crossref","first-page":"e0130142","DOI":"10.1371\/journal.pone.0130142","article-title":"Differential activity of Nivolumab, Pembrolizumab and MPDL3280A according to the tumor expression of programmed Death\u2010Ligand\u20101 (PD\u2010L1): sensitivity analysis of trials in melanoma, lung and Genitourinary cancers","volume":"10","author":"Carbognin L","year":"2016","journal-title":"PLoS ONE"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-017-0299-1"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)00561-4"},{"key":"e_1_2_8_37_1","first-page":"748","article-title":"Atezolizumab versus chemotherapy in patients with platinum\u2010treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open\u2010label, phase 3 randomised controlled trial","volume":"10122","author":"Powles T","year":"2017","journal-title":"Lancet"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)32455-2"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30065-7"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1613683"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.35.6_suppl.284"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.2411"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.71.6795"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.59.4358"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-016-0191-4"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2017.12.007"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2018.06.002"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-0077-T"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3817"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12965"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.22"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.04.038"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euf.2015.09.007"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13904"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2017.05.032"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2016.10.017"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2017.07.010"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00307-1"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1003466"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1200694"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2015.11.016"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.53.0105"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.27969"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1505197"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx286"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504030"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.2217\/imt.15.87"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1302369"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2000.18.2.363"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2018.36.6_suppl.414"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.56.2736"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)01281-7"}],"container-title":["BJU International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbju.14643","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bjui-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bju.14643","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T11:31:41Z","timestamp":1761737501000},"score":1,"resource":{"primary":{"URL":"https:\/\/bjui-journals.onlinelibrary.wiley.com\/doi\/10.1111\/bju.14643"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,22]]},"references-count":71,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,6]]}},"alternative-id":["10.1111\/bju.14643"],"URL":"https:\/\/doi.org\/10.1111\/bju.14643","archive":["Portico"],"relation":{},"ISSN":["1464-4096","1464-410X"],"issn-type":[{"value":"1464-4096","type":"print"},{"value":"1464-410X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,22]]},"assertion":[{"value":"2019-01-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}