{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:20:19Z","timestamp":1786123219252,"version":"build-2736575974"},"reference-count":21,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The prognostic significance of non-muscle-invasive bladder cancer (NMIBC) recurrence after a prolonged disease-free interval following intravesical Bacillus Calmette\u2013Gu\u00e9rin (BCG) therapy remains unclear. This multicenter study evaluated the impact of late recurrence after BCG therapy on oncological outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective multicenter study used the Japan Urological Oncology Group database. Among 3226 patients treated with intravesical BCG for NMIBC, 238 with non-muscle-invasive intravesical recurrence \u22651\u00a0year after initial BCG therapy were analyzed, after excluding those with muscle-invasive recurrence at first recurrence. Patients were stratified by time to recurrence: 1\u20132\u00a0years and\u00a0\u2265\u00a02\u00a0years. Progression-free survival (PFS) and cancer-specific survival (CSS) were assessed using Kaplan\u2013Meier and Cox proportional hazards analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>During a median follow-up of 72.7\u00a0months, the 5-year PFS and CSS rates were 90.8% and 91.5%, respectively. PFS did not differ significantly between the 1\u20132-year and\u00a0\u2265\u00a02-year recurrence groups (log-rank p\u00a0=\u00a00.300). In contrast, recurrence \u22652\u00a0years was associated with significantly worse CSS than recurrence at 1\u20132\u00a0years (log-rank P\u00a0=\u00a0.018) and was a significant predictor of worse CSS in univariate analysis (hazard ratio, 8.06; 95% confidence interval, 1.02\u201362.6; P\u00a0=\u00a0.047). Repeat BCG therapy did not significantly improve PFS or CSS in patients with recurrence \u22652\u00a0years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>NMIBC recurrence occurring \u22652\u00a0years after initial BCG therapy may be associated with poorer cancer-specific survival despite similar progression-free survival. Late recurrence should not automatically be considered a favorable prognostic subgroup, and careful surveillance and risk stratification are warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jjco\/hyag124","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T11:19:25Z","timestamp":1785151165000},"source":"Crossref","is-referenced-by-count":0,"title":["Prognostic significance of non\u2013muscle-invasive late recurrence after intravesical bacillus Calmette\u2013Gu\u00e9rin therapy in bladder cancer: a multicenter, retrospective real-world study (the Japan Urological Oncology Group)"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5079-2171","authenticated-orcid":false,"given":"Yoshinori","family":"Ikehata","sequence":"first","affiliation":[{"name":"Department of Urology, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naotaka","family":"Nishiyama","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9503-7356","authenticated-orcid":false,"given":"Makito","family":"Miyake","sequence":"additional","affiliation":[{"name":"Department of Urology, Nara Medical University, 840 Shijocho, Kashihara, Nara, 634-8521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobutaka","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Department of Urology, Nara Medical University, 840 Shijocho, Kashihara, Nara, 634-8521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kita","family":"Yuki","sequence":"additional","affiliation":[{"name":"Department of Urology, Kyoto University Graduate School of Medicine , Yoshidakonoecho, Sakyo-ku, Kyoto, Kyoto , 606-8501,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soichiro","family":"Shimura","sequence":"additional","affiliation":[{"name":"Department of Urology, Kitasato University School of Medicine , 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa ,","place":["252-0373, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuta","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Urology, Kyoto Prefectural University of Medicine , 465 Kajii\u2011cho, Kamigyo\u2011ku, Kyoto, 602\u20110841 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1570-6340","authenticated-orcid":false,"given":"Takashi","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Urology, Graduate School of Medical Sciences, Kyushu University , 3\u20111\u20111 Maidashi, Higashi\u2011ku, Fukuoka 812\u20118582,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2300-8446","authenticated-orcid":false,"given":"Shugo","family":"Yajima","sequence":"additional","affiliation":[{"name":"Department of Urology, National Cancer Center Hospital East , 6\u20115\u20111 Kashiwanoha, Kashiwa, Chiba 277\u20118577,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyuki","family":"Nagumo","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, University of Tsukuba , 1\u20111\u20111 Tennodai, Tsukuba, Ibaraki 305\u20118577,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichi","family":"Morizane","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery, Faculty of Medicine, Tottori University , 86 Nishimachi, Yonago, Tottori 683\u20118503,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuma","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Urology, Tohoku University , 2\u20111 Seiryo\u2011cho, Aoba\u2011ku, Sendai 980\u20118575,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Fujii","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, University of Miyazaki , 5200 Kihara, Kiyotake\u2011cho, Miyazaki, Miyazaki 889\u20111692 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8902-7853","authenticated-orcid":false,"given":"Tomokazu","family":"Sazuka","sequence":"additional","affiliation":[{"name":"Department of Urology, Chiba University Graduate School of Medicine , 1\u20118\u20111 Inohana, Chuo\u2011ku, Chiba, Chiba 260\u20118670,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0026-4079","authenticated-orcid":false,"given":"Shingo","family":"Hatakeyama","sequence":"additional","affiliation":[{"name":"Department of Urology, Hirosaki University Graduate School of Medicine , 5 Zaifu\u2011cho, Hirosaki, Aomori 036\u20118562 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3031-7258","authenticated-orcid":false,"given":"Katsuyoshi","family":"Hashine","sequence":"additional","affiliation":[{"name":"Department of Urology, National Hospital Organization Shikoku Cancer Center , 160 Kou Minami\u2011Umemoto\u2011cho, Matsuyama, Ehime 791\u20110280 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Yamagishi","sequence":"additional","affiliation":[{"name":"Department of Urology, Yamagata University Faculty of Medicine , 2\u20112\u20112 Iida\u2011Nishi, Yamagata 990\u20119585 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikiya","family":"Taoka","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, Kagawa University , 1750\u20111 Ikedo, Miki\u2011cho, Kida\u2011gun, Kagawa 761\u20110793 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyuki","family":"Matsui","sequence":"additional","affiliation":[{"name":"Department of Urology, National Cancer Center Hospital , 5\u20111\u20111 Tsukiji, Chuo\u2011ku, Tokyo 104\u20110045 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyohide","family":"Fujimoto","sequence":"additional","affiliation":[{"name":"Department of Urology, Nara Medical University, 840 Shijocho, Kashihara, Nara, 634-8521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Nishiyama","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, University of Tsukuba , 1\u20111\u20111 Tennodai, Tsukuba, Ibaraki 305\u20118577,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiichiro","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Urology, The Jikei University School of Medicine , 3\u201119\u201118 Nishi\u2011Shimbashi, Minato\u2011ku, Tokyo 105\u20118471 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5673-1553","authenticated-orcid":false,"given":"Takahiro","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Urology, The Jikei University School of Medicine , 3\u201119\u201118 Nishi\u2011Shimbashi, Minato\u2011ku, Tokyo 105\u20118471 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kitamura","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, University of Toyama , 2630 Sugitani, Toyama, Toyama, 930-0194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Japanese Urological Oncology Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"2026080709472276600_ref1","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.eururo.2012.07.033","article-title":"Epidemiology and risk factors of urothelial bladder cancer","volume":"63","author":"Burger","year":"2013","journal-title":"Eur Urol"},{"key":"2026080709472276600_ref2","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1016\/j.eururo.2024.10.012","article-title":"Bladder cancer incidence and mortality: global overview and recent trends","volume":"87","author":"Filho","year":"2025","journal-title":"Eur Urol"},{"key":"2026080709472276600_ref3","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1016\/S0022-5347(05)67707-5","article-title":"Maintenance bacillus Calmette\u2013Gu\u00e9rin immunotherapy for recurrent Ta, T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized southwest oncology group study","volume":"163","author":"Lamm","year":"2000","journal-title":"J Urol"},{"key":"2026080709472276600_ref4","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1016\/S0302-2838(02)00079-8","article-title":"Bacillus Calmette\u2013Gu\u00e9rin versus chemotherapy for the intravesical treatment of patients with carcinoma in situ of the bladder: a meta-analysis of randomized trials","volume":"41","author":"Sylvester","year":"2002","journal-title":"Eur Urol"},{"key":"2026080709472276600_ref5","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1016\/j.eururo.2014.05.038","article-title":"Expert consensus document: consensus statement on best practice management regarding the use of intravesical immunotherapy with BCG for bladder cancer","volume":"66","author":"Kamat","year":"2014","journal-title":"Eur Urol"},{"key":"2026080709472276600_ref6","volume-title":"EAU guidelines on non\u2013muscle-invasive bladder cancer (TaT1 and CIS)","author":"European Association of Urology","year":"2025"},{"key":"2026080709472276600_ref7","volume-title":"Plymouth meeting","author":"Thomas W Flaig. National Comprehensive Cancer Network","year":"2025"},{"key":"2026080709472276600_ref8","doi-asserted-by":"publisher","first-page":"1935","DOI":"10.1200\/JCO.2015.64.4070","article-title":"Definitions, end points, and clinical trial designs for non\u2013muscle-invasive bladder cancer: recommendations from the international bladder cancer group","volume":"34","author":"Kamat","year":"2016","journal-title":"J Clin Oncol"},{"key":"2026080709472276600_ref9","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.eururo.2021.08.010","article-title":"EAU guidelines on non\u2013muscle-invasive urothelial carcinoma of the bladder: update 2022","volume":"81","author":"Babjuk","year":"2022","journal-title":"Eur Urol"},{"key":"2026080709472276600_ref10","doi-asserted-by":"publisher","first-page":"6547","DOI":"10.21037\/tcr-20-1514","article-title":"Role of immunotherapy in BCG-unresponsive non-muscle-invasive bladder cancer","volume":"9","author":"Suh","year":"2020","journal-title":"Transl Cancer Res"},{"key":"2026080709472276600_ref11","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.clgc.2024.08.015","article-title":"Real-world treatment patterns and clinical outcomes of patients with BCG-unresponsive high-risk non\u2013muscle-invasive bladder cancer","volume":"23","author":"Kulkarni","year":"2025","journal-title":"Clin Genitourin Cancer"},{"key":"2026080709472276600_ref12","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1186\/s12885-021-07966-7","article-title":"Non-maintenance intravesical bacillus Calmette\u2013Gu\u00e9rin induction therapy with eight doses in patients with high- or highest-risk non-muscle invasive bladder cancer: a retrospective non-randomized comparative study","volume":"21","author":"Miyake","year":"2021","journal-title":"BMC Cancer"},{"key":"2026080709472276600_ref13","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1038\/nrurol.2014.15","article-title":"The mechanism of action of BCG therapy for bladder cancer\u2014a current perspective","volume":"11","author":"Redelman-Sidi","year":"2014","journal-title":"Nat Rev Urol"},{"key":"2026080709472276600_ref14","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1126\/science.1203486","article-title":"Cancer immunoediting: integrating immunity\u2019s roles in cancer suppression and promotion","volume":"331","author":"Schreiber","year":"2011","journal-title":"Science"},{"key":"2026080709472276600_ref15","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1038\/ni1102-991","article-title":"Cancer immunoediting: from immunosurveillance to tumor escape","volume":"3","author":"Dunn","year":"2002","journal-title":"Nat Immunol"},{"key":"2026080709472276600_ref16","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1038\/s41392-025-02371-z","article-title":"Immunosenescence: signaling pathways, diseases and therapeutic targets","volume":"10","author":"Fu","year":"2025","journal-title":"Signal Transduct Target Ther"},{"key":"2026080709472276600_ref17","doi-asserted-by":"publisher","first-page":"306.e1","DOI":"10.1016\/j.urolonc.2018.02.005","article-title":"Does switching the bacillus Calmette-Gu\u00e9rin strain affect clinical outcome in patients with recurrent non\u2013muscle-invasive bladder cancer after initial bacillus Calmette-Gu\u00e9rin therapy?","volume":"36","author":"Niwa","year":"2018","journal-title":"Urol Oncol"},{"key":"2026080709472276600_ref18","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.eururo.2021.12.005","article-title":"Clinical trial design for patients with bacillus Calmette-Gu\u00e9rin\u2013exposed high-risk non\u2013muscle-invasive bladder cancer: recommendations from the international bladder cancer group","volume":"82","author":"Bivalacqua","year":"2022","journal-title":"Eur Urol"},{"key":"2026080709472276600_ref19","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1016\/S0090-4295(99)00591-9","article-title":"Long-term results of intravesical bacillus Calmette-Gu\u00e9rin therapy for stage T1 superficial bladder cancer","volume":"55","author":"Brake","year":"2000","journal-title":"Urology"},{"key":"2026080709472276600_ref20","doi-asserted-by":"publisher","first-page":"215","DOI":"10.3233\/BLC-150039","article-title":"Bacillus Calmette-Gu\u00e9rin (BCG) treatment failures with non\u2013muscle-invasive bladder cancer: a data-driven definition for BCG-unresponsive disease","volume":"2","author":"Steinberg","year":"2016","journal-title":"Bladder Cancer"},{"key":"2026080709472276600_ref21","doi-asserted-by":"publisher","first-page":"e71243","DOI":"10.1002\/cam4.71243","article-title":"Mechanisms, clinical trials, and new treatments for BCG-unresponsive in nonmuscle invasive bladder cancer","volume":"14","author":"Huang","year":"2025","journal-title":"Cancer Med"}],"container-title":["Japanese Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jjco\/advance-article-pdf\/doi\/10.1093\/jjco\/hyag124\/70530047\/hyag124.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jjco\/advance-article-pdf\/doi\/10.1093\/jjco\/hyag124\/70530047\/hyag124.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T13:47:28Z","timestamp":1786110448000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jjco\/advance-article\/doi\/10.1093\/jjco\/hyag124\/8754026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,7]]},"references-count":21,"URL":"https:\/\/doi.org\/10.1093\/jjco\/hyag124","relation":{},"ISSN":["1465-3621"],"issn-type":[{"value":"1465-3621","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,7]]},"article-number":"hyag124"}}