{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T22:05:35Z","timestamp":1772316335103,"version":"3.50.1"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T00:00:00Z","timestamp":1679875200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T00:00:00Z","timestamp":1679875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100016112","name":"Universit\u00e0 di Foggia","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100016112","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["World J Urol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>Radical cystectomy (RC) is the standard treatment for high-risk non muscle-invasive bladder cancer (NMIBC) failing first BCG treatment. A second BCG course is an option for those patients who refuse RC or are not eligible for it, but its success rate is quite low. Aim of the present study was to determine whether the addition of intravesical electromotive drug administration of mytomicin-C (EMDA-MMC) improved the efficacy of second BCG course.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Patients with high-risk NMIBC having failed first BCG treatment and having refused RC were offered a second BCG induction course either alone (group A) or combined with EMDA-MMC (group B). Recurrence-free survival (RFS), progression-free survival (PFS) and cancer-specific survival (CSS) were tested.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Of the 80 evaluable patients, 44 were in group A and 36 in group B; median follow-up was 38\u00a0months. RFS was significantly worse in group A whereas there was no difference in PFS and CSS between the two groups. Stratifying by disease stage, Ta patients receiving combined treatment had statistically better RFS and PFS survival than those receiving BCG only; this difference did not apply to T1 patients. Multivariable analysis confirmed that combined treatment was a significant predictor of recurrence and was close to predict progression. No tested variable was predictive of recurrence or progression in T1 tumours. Among those who underwent RC, CSS was 61.5% in those who had progression and 100% in those who remained with NMIBC.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Combined treatment improved RFS and PFS only in patients with Ta disease.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00345-023-04372-5","type":"journal-article","created":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T05:02:47Z","timestamp":1679893367000},"page":"1329-1335","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Conservative treatment for high-risk NMIBC failing BCG treatment: who benefits from adding electromotive drug administration (EMDA) of mitomycin C (MMC) to a second BCG induction cycle?"],"prefix":"10.1007","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7291-0316","authenticated-orcid":false,"given":"Gian Maria","family":"Busetto","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Finati","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Chirico","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Cinelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"D\u2019Altilia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ugo G.","family":"Falagario","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Sanguedolce","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Del Giudice","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ettore","family":"De Berardinis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Ferro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felice","family":"Crocetto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo","family":"Porreca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Di Gianfrancesco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beppe","family":"Calo\u2019","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vito","family":"Mancini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Bettocchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Carrieri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi","family":"Cormio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,3,27]]},"reference":[{"key":"4372_CR1","unstructured":"Babjuk M, Burger M, Comp\u00e9rat E, Gontero P, Mostafid AH, Palou J et al (2021) Guidelines on non-muscle invasive bladder cancer 2020, Update March 2021. https:\/\/uroweb.org\/guideline\/non-muscle-invasive-bladder-cancer\/"},{"issue":"1","key":"4372_CR2","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.eururo.2016.02.028","volume":"70","author":"PA Humphrey","year":"2016","unstructured":"Humphrey PA, Moch H, Cubilla AL, Ulbright TM, Reuter VE (2016) The 2016 WHO classification of tumours of the urinary system and male genital organs-part B: prostate and bladder tumours. Eur Urol 70(1):106\u2013119","journal-title":"Eur Urol"},{"issue":"4","key":"4372_CR3","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1016\/j.eururo.2017.12.018","volume":"73","author":"GP Paner","year":"2018","unstructured":"Paner GP, Stadler WM, Hansel DE, Montironi R, Lin DW, Amin MB (2018) Updates in the eighth edition of the tumor-node-metastasis staging classification for urologic cancers. Eur Urol 73(4):560\u2013569","journal-title":"Eur Urol"},{"issue":"4","key":"4372_CR4","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1016\/j.urology.2003.11.049","volume":"63","author":"A B\u00f6hle","year":"2004","unstructured":"B\u00f6hle A, Bock PR (2004) Intravesical bacille Calmette-Gu\u00e9rin versus mitomycin C in superficial bladder cancer: formal meta-analysis of comparative studies on tumor progression. Urology 63(4):682\u2013686","journal-title":"Urology"},{"issue":"3","key":"4372_CR5","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1016\/j.eururo.2012.10.039","volume":"63","author":"J Oddens","year":"2013","unstructured":"Oddens J, Brausi M, Sylvester R, Bono A, van de Beek C, van Andel G et al (2013) Final results of an EORTC-GU cancers group randomized study of maintenance bacillus Calmette-Gu\u00e9rin in intermediate- and high-risk Ta, T1 papillary carcinoma of the urinary bladder: one-third dose versus full dose and 1 year versus 3 years of maintenance. Eur Urol 63(3):462\u2013472","journal-title":"Eur Urol"},{"issue":"2","key":"4372_CR6","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.urolonc.2007.11.033","volume":"27","author":"SP Lerner","year":"2009","unstructured":"Lerner SP, Tangen CM, Sucharew H, Wood D, Crawford ED (2009) Failure to achieve a complete response to induction BCG therapy is associated with increased risk of disease worsening and death in patients with high risk non-muscle invasive bladder cancer. Urol Oncol 27(2):155\u2013159","journal-title":"Urol Oncol"},{"issue":"3","key":"4372_CR7","doi-asserted-by":"publisher","first-page":"108.e1\u20134","DOI":"10.1016\/j.urolonc.2014.02.020","volume":"33","author":"HW Herr","year":"2015","unstructured":"Herr HW, Milan TN, Dalbagni G (2015) BCG-refractory vs BCG-relapsing non-muscle-invasive bladder cancer: a prospective cohort outcomes study. Urol Oncol 33(3):108.e1\u20134","journal-title":"Urol Oncol"},{"issue":"1","key":"4372_CR8","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/S1470-2045(05)70472-1","volume":"7","author":"SM Di Stasi","year":"2006","unstructured":"Di Stasi SM, Giannantoni A, Giurioli A, Valenti M, Zampa G, Storti L et al (2006) Sequential BCG and electromotive mitomycin versus BCG alone for high-risk superficial bladder cancer: a randomised controlled trial. Lancet Oncol 7(1):43\u201351","journal-title":"Lancet Oncol"},{"issue":"1","key":"4372_CR9","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.1186\/s12885-018-5134-7","volume":"18","author":"M Racioppi","year":"2018","unstructured":"Racioppi M, Di Gianfrancesco L, Ragonese M, Palermo G, Sacco E, Bassi PF (2018) Electro motive drug administration (EMDA) of mitomycin C as first-line salvage therapy in high risk \u201cBCG failure\u201d non muscle invasive bladder cancer: 3 years follow-up outcomes. BMC Cancer 18(1):1224","journal-title":"BMC Cancer"},{"issue":"2","key":"4372_CR10","doi-asserted-by":"publisher","first-page":"e100","DOI":"10.1016\/j.clgc.2020.11.002","volume":"19","author":"L Di Gianfrancesco","year":"2021","unstructured":"Di Gianfrancesco L, Ragonese M, Palermo G, Sacco E, Bassi P, Racioppi M (2021) Second-line conservative device-assisted intravesical treatment in selected patients with recurrent high-risk non-muscle-invasive bladder cancer. Clin Genitourin Cancer 19(2):e100\u2013e119","journal-title":"Clin Genitourin Cancer"},{"issue":"10","key":"4372_CR11","doi-asserted-by":"publisher","first-page":"3815","DOI":"10.1007\/s00345-021-03690-w","volume":"39","author":"B Cal\u00f2","year":"2021","unstructured":"Cal\u00f2 B, Sanguedolce F, Falagario UG, Chirico M, Fortunato F, Carvalho-Diaz E et al (2021) Assessing treatment response after intravesical bacillus Calmette-Guerin induction cycle: are routine bladder biopsies necessary? World J Urol 39(10):3815\u20133821","journal-title":"World J Urol"},{"issue":"3","key":"4372_CR12","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1016\/j.juro.2011.04.073","volume":"186","author":"HM Rosevear","year":"2011","unstructured":"Rosevear HM, Lightfoot AJ, Birusingh KK, Maym\u00ed JL, Nepple KG, O\u2019Donnell MA et al (2011) Factors affecting response to bacillus Calmette-Guerin plus interferon for urothelial carcinoma in situ. J Urol 186(3):817\u2013823","journal-title":"J Urol"},{"issue":"3","key":"4372_CR13","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1111\/bju.13088","volume":"117","author":"PA Cockerill","year":"2016","unstructured":"Cockerill PA, Knoedler JJ, Frank I, Tarrell R, Karnes RJ (2016) Intravesical gemcitabine in combination with mitomycin C as salvage treatment in recurrent non-muscle-invasive bladder cancer. BJU Int 117(3):456\u2013462","journal-title":"BJU Int"},{"issue":"8","key":"4372_CR14","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1111\/j.1464-410X.2009.08543.x","volume":"104","author":"L Barlow","year":"2009","unstructured":"Barlow L, McKiernan J, Sawczuk I, Benson M (2009) A single-institution experience with induction and maintenance intravesical docetaxel in the management of non-muscle-invasive bladder cancer refractory to bacille Calmette-Gu\u00e9rin therapy. BJU Int 104(8):1098\u20131102","journal-title":"BJU Int"},{"issue":"3","key":"4372_CR15","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1016\/S0022-5347(05)67799-3","volume":"163","author":"G Steinberg","year":"2000","unstructured":"Steinberg G, Bahnson R, Brosman S, Middleton R, Wajsman Z, Wehle M (2000) Efficacy and safety of valrubicin for the treatment of Bacillus Calmette-Guerin refractory carcinoma in situ of the bladder. The Valrubicin Study Group. J Urol 163(3):761\u2013767","journal-title":"J Urol"},{"issue":"7","key":"4372_CR16","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1016\/S1470-2045(21)00147-9","volume":"22","author":"AV Balar","year":"2021","unstructured":"Balar AV, Kamat AM, Kulkarni GS, Uchio EM, Boormans JL, Roumigui\u00e9 M et al (2021) Pembrolizumab monotherapy for the treatment of high-risk non-muscle-invasive bladder cancer unresponsive to BCG (KEYNOTE-057): an open-label, single-arm, multicentre, phase 2 study. Lancet Oncol 22(7):919\u2013930","journal-title":"Lancet Oncol"},{"issue":"1","key":"4372_CR17","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/S1470-2045(20)30540-4","volume":"22","author":"SA Boorjian","year":"2021","unstructured":"Boorjian SA, Alemozaffar M, Konety BR, Shore ND, Gomella LG, Kamat AM et al (2021) Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial. Lancet Oncol 22(1):107\u2013117","journal-title":"Lancet Oncol"},{"issue":"1","key":"4372_CR18","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.eururo.2018.09.005","volume":"75","author":"WS Tan","year":"2019","unstructured":"Tan WS, Panchal A, Buckley L, Devall AJ, Loubi\u00e8re LS, Am P et al (2019) Radiofrequency-induced thermo-chemotherapy effect versus a second course of bacillus calmette-gu\u00e9rin or institutional standard in patients with recurrence of non-muscle-invasive bladder cancer following induction or maintenance Bacillus Calmette-Gu\u00e9rin Therapy (HYMN): a phase III, open-label, randomised controlled trial. Eur Urol 75(1):63\u201371","journal-title":"Eur Urol"},{"issue":"11","key":"4372_CR19","doi-asserted-by":"publisher","first-page":"8509","DOI":"10.1016\/j.urolonc.2020.06.031","volume":"38","author":"T Juvet","year":"2020","unstructured":"Juvet T, Mari A, Lajkosz K, Wallis C, Kuk C, Erlich A et al (2020) Sequential administration of Bacillus Calmette-Guerin (BCG) and electromotive drug administration (EMDA) of mitomycin C (MMC) for the treatment of high-grade nonmuscle invasive bladder cancer after BCG failure. Urol Oncol 38(11):8509\u201385015","journal-title":"Urol Oncol"},{"issue":"15","key":"4372_CR20","doi-asserted-by":"publisher","first-page":"25433","DOI":"10.18632\/oncotarget.15989","volume":"8","author":"L Cormio","year":"2017","unstructured":"Cormio L, Sanguedolce F, Cormio A, Massenio P, Pedicillo MC, Cagiano S et al (2017) Human epidermal growth factor receptor 2 expression is more important than Bacillus Calmette Guerin treatment in predicting the outcome of T1G3 bladder cancer. Oncotarget 8(15):25433\u201325441","journal-title":"Oncotarget"},{"issue":"4","key":"4372_CR21","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1007\/s00432-018-2593-9","volume":"144","author":"F Sanguedolce","year":"2018","unstructured":"Sanguedolce F, Cormio A, Massenio P, Pedicillo MC, Cagiano S, Fortunato F et al (2018) Altered expression of HER-2 and the mismatch repair genes MLH1 and MSH2 predicts the outcome of T1 high-grade bladder cancer. J Cancer Res Clin Oncol 144(4):637\u2013644","journal-title":"J Cancer Res Clin Oncol"},{"key":"4372_CR22","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2022.103577","volume":"170","author":"F Crocetto","year":"2022","unstructured":"Crocetto F, Barone B, Ferro M, Busetto GM, La Civita E, Buonerba C et al (2022) Liquid biopsy in bladder cancer: state of the art and future perspectives. Crit Rev Oncol Hematol 170:103577","journal-title":"Crit Rev Oncol Hematol"},{"issue":"5","key":"4372_CR23","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1634\/theoncologist.2018-0784","volume":"24","author":"C Nicolazzo","year":"2019","unstructured":"Nicolazzo C, Busetto GM, Gradilone A, Sperduti I, Del Giudice F, Loreni F et al (2019) Circulating tumor cells identify patients with super-high-risk non-muscle-invasive bladder cancer: updated outcome analysis of a prospective single-center trial. Oncologist 24(5):612\u2013616","journal-title":"Oncologist"}],"container-title":["World Journal of Urology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00345-023-04372-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00345-023-04372-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00345-023-04372-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T11:05:52Z","timestamp":1684235152000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00345-023-04372-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,27]]},"references-count":23,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["4372"],"URL":"https:\/\/doi.org\/10.1007\/s00345-023-04372-5","relation":{},"ISSN":["1433-8726"],"issn-type":[{"value":"1433-8726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,27]]},"assertion":[{"value":"16 January 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 March 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 March 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Authors have no potential conflict of interest to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Ethical Committee of Policlinico Riuniti of Foggia on 15th of March 2022 (Approval Code 31\/CE\/2022). All patients signed an informed consent for the procedure.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Human and animal rights"}}]}}