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Patients were randomized 1:1 to receive intravesical BCG for 1\u00a0year (once weekly for 6\u00a0weeks plus subsequent maintenance) or HIVEC with 40\u00a0mg MMC, administered using the Combat BRS system\u00a0(once weekly instillations were given for 6\u00a0weeks, followed by once monthly instillation for 6\u00a0months). Total recirculating dwell time for HIVEC was 60\u00a0min at a target temperature of 43\u00b0\u2009\u00b1\u20090.5\u00a0\u00b0C. Primary endpoint was recurrence-free survival. Secondary endpoints were time to recurrence, progression-free survival, cancer-specific survival, and overall survival at 24\u00a0months. Adverse events were routinely assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fifty patients were enrolled. Mean age was 73.5\u00a0years. Median follow-up was 33.7\u00a0months. Recurrence-free survival at 24\u00a0months was 86.5% for HIVEC and 71.8% for BCG (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.184) in the intention-to-treat analysis and 95.0% for HIVEC and 75.1% for BCG (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.064) in the per protocol analysis. Time to recurrence was 21.5 and 16.1\u00a0months for HIVEC and BCG, respectively. Progression-free survival for HIVEC vs BCG was 95.7% vs 71.8% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.043) in the intention-to-treat analysis and 100% vs 75.1% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.018) in the per protocol analysis, respectively. Cancer-specific survival at 24\u00a0months was 100% for both groups and overall survival was 91.5% for HIVEC vs 81.8% for BCG.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>HIVEC provides comparable safety and efficacy to BCG and is a reasonable alternative during BCG shortages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>EudraCT 2016-001186-85. Date of registration: 17 March 2016.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00345-022-03928-1","type":"journal-article","created":{"date-parts":[[2022,8,13]],"date-time":"2022-08-13T07:02:42Z","timestamp":1660374162000},"page":"999-1004","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Recirculating hyperthermic intravesical chemotherapy with mitomycin C (HIVEC) versus BCG in high-risk non-muscle-invasive bladder cancer: results of the HIVEC-HR randomized clinical trial"],"prefix":"10.1007","volume":"40","clinical-trial-number":[{"clinical-trial-number":"2016-001186-85","registry":"10.18810\/euctr"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0767-3465","authenticated-orcid":false,"given":"F\u00e9lix","family":"Guerrero-Ramos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Gonz\u00e1lez-Padilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Gonz\u00e1lez-D\u00edaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"de la Rosa-Kehrmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Rodr\u00edguez-Antol\u00edn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brant A.","family":"Inman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Villacampa-Aub\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,17]]},"reference":[{"issue":"1","key":"3928_CR1","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.eururo.2015.06.045","volume":"69","author":"S Cambier","year":"2016","unstructured":"Cambier S, Sylvester RJ, Collette L et al (2016) EORTC Nomograms and risk groups for predicting recurrence, progression, and disease-specific and overall survival in non-muscle-invasive stage Ta-T1 urothelial bladder cancer patients treated with 1\u20133 years of maintenance bacillus Calmette-Gu\u00e9rin. 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Guerrero-Ramos and B. A. Inman have received consultancy honoraria from Combat Medical Ltd.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study was approved by the Spanish Agency for Medicines and Health Products (AEMPS) and local Ethics Committees.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"All patients signed an informed consent for the study, which was also approved by local Ethics Committees.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}}]}}