{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:22:21Z","timestamp":1791516141394,"version":"4.3.4"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":71,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-026-55917-8","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T08:23:10Z","timestamp":1780388590000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A machine-learning approach to predict additional treatment after Bacillus Calmette-Gu\u00e9rin induction in non-muscle-invasive bladder cancer"],"prefix":"10.1038","volume":"16","author":[{"given":"Philippe","family":"Pinton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruna","family":"Kawano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Patschan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjun","family":"Ravi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Nakano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Auvaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apurba","family":"Mukherjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"55917_CR1","unstructured":"World Health Organization. International Agency for Research on Cancer. Cancer data visualization., https:\/\/gco.iarc.fr\/today\/en\/dataviz\/bars?mode=cancer&key=total&cancers=30&group_populations=1&populations=900 (accessed 10 Feb 2026)."},{"key":"55917_CR2","doi-asserted-by":"publisher","first-page":"04109","DOI":"10.7189\/jogh.13.04109","volume":"13","author":"Y Zhang","year":"2023","unstructured":"Zhang, Y. et al. The global landscape of bladder cancer incidence and mortality in 2020 and projections to 2040. J. Glob. Health. 13, 04109. https:\/\/doi.org\/10.7189\/jogh.13.04109 (2023).","journal-title":"J. Glob. Health"},{"key":"55917_CR3","first-page":"43","volume":"22","author":"RS Matulewicz","year":"2020","unstructured":"Matulewicz, R. S. & Steinberg, G. D. Non-muscle-invasive bladder cancer: Overview and contemporary treatment landscape of neoadjuvant chemoablative therapies. Rev. Urol. 22, 43\u201351 (2020).","journal-title":"Rev. Urol."},{"key":"55917_CR4","doi-asserted-by":"publisher","first-page":"e471942","DOI":"10.1200\/edbk-25-471942","volume":"45","author":"M Filon","year":"2025","unstructured":"Filon, M. & Schmidt, B. New treatment options for non-muscle-invasive bladder cancer. Am. Soc. Clin. Oncol. Educ. Book. 45, e471942. https:\/\/doi.org\/10.1200\/edbk-25-471942 (2025).","journal-title":"Am. Soc. Clin. Oncol. Educ. Book."},{"key":"55917_CR5","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1007\/s11912-022-01350-9","volume":"25","author":"HA Al","year":"2023","unstructured":"Al, H. A., Awamlh, B. & Chang, S. S. Novel therapies for high-risk non-muscle invasive bladder cancer. Curr. Oncol. Rep. 25, 83\u201391. https:\/\/doi.org\/10.1007\/s11912-022-01350-9 (2023).","journal-title":"Curr. Oncol. Rep."},{"key":"55917_CR6","doi-asserted-by":"publisher","first-page":"3056","DOI":"10.21037\/tau.2019.09.38","volume":"9","author":"LHC Kim","year":"2020","unstructured":"Kim, L. H. C. & Patel, M. I. Transurethral resection of bladder tumour (TURBT). Transl. Androl. Urol. 9, 3056\u20133072. https:\/\/doi.org\/10.21037\/tau.2019.09.38 (2020).","journal-title":"Transl. Androl. Urol."},{"key":"55917_CR7","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1159\/000533410","volume":"102","author":"H Li","year":"2024","unstructured":"Li, H. et al. Analysis of risk factors for recurrence after transurethral resection of bladder tumor in patients with non-muscle invasive bladder cancer: 2-Year follow-up outcomes. Oncology 102, 337\u2013342. https:\/\/doi.org\/10.1159\/000533410 (2024).","journal-title":"Oncology"},{"issue":"17","key":"55917_CR8","doi-asserted-by":"publisher","first-page":"1890","DOI":"10.1200\/JCO.21.02554","volume":"40","author":"AV Balar","year":"2022","unstructured":"Balar, A. V. et al. Pembrolizumab monotherapy for high-risk BCG-unresponsive non-muscle-invasive bladder cancer: updated results from the phase 2 KEYNOTE-057 study. J. Clin. Oncol. 40 (17), 1890\u20131898. https:\/\/doi.org\/10.1200\/JCO.21.02554 (2022).","journal-title":"J. Clin. Oncol."},{"issue":"3","key":"55917_CR9","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/S1470-2045(23)00645-9","volume":"25","author":"K Chamie","year":"2024","unstructured":"Chamie, K. et al. N-803 plus BCG for BCG-unresponsive non-muscle-invasive bladder cancer (QUILT-3.032): results from a phase 2\/3 multicentre study. Lancet Oncol. 25 (3), 301\u2013312. https:\/\/doi.org\/10.1016\/S1470-2045(23)00645-9 (2024).","journal-title":"Lancet Oncol."},{"key":"55917_CR10","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.clim.2014.10.005","volume":"155","author":"J Kleinnijenhuis","year":"2014","unstructured":"Kleinnijenhuis, J. et al. BCG-induced trained immunity in NK cells: Role for non-specific protection to infection. Clin. Immunol. 155, 213\u2013219. https:\/\/doi.org\/10.1016\/j.clim.2014.10.005 (2014).","journal-title":"Clin. Immunol."},{"key":"55917_CR11","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1093\/intimm\/dxn073","volume":"20","author":"E Marcenaro","year":"2008","unstructured":"Marcenaro, E., Ferranti, B., Falco, M., Moretta, L. & Moretta, A. Human NK cells directly recognize Mycobacterium bovis via TLR2 and acquire the ability to kill monocyte-derived DC. Int. Immunol. 20, 1155\u20131167. https:\/\/doi.org\/10.1093\/intimm\/dxn073 (2008).","journal-title":"Int. Immunol."},{"key":"55917_CR12","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1016\/s0022-5347(17)49104-x","volume":"133","author":"JB deKernion","year":"1985","unstructured":"deKernion, J. B., Huang, M. Y., Lindner, A., Smith, R. B. & Kaufman, J. J. The management of superficial bladder tumors and carcinoma in situ with intravesical bacillus Calmette-Guerin. J. Urol. 133, 598\u2013601. https:\/\/doi.org\/10.1016\/s0022-5347(17)49104-x (1985).","journal-title":"J. Urol."},{"key":"55917_CR13","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1186\/s12885-021-07966-7","volume":"21","author":"M Miyake","year":"2021","unstructured":"Miyake, M. et al. Non-maintenance intravesical Bacillus Calmette-Gu\u00e9rin induction therapy with eight doses in patients with high- or highest-risk non-muscle invasive bladder cancer: a retrospective non-randomized comparative study. BMC Cancer. 21, 266. https:\/\/doi.org\/10.1186\/s12885-021-07966-7 (2021).","journal-title":"BMC Cancer"},{"key":"55917_CR14","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1111\/iju.14281","volume":"27","author":"H Matsumoto","year":"2020","unstructured":"Matsumoto, H. et al. Clinical practice guidelines for bladder cancer 2019 update by the Japanese Urological Association: Summary of the revision. Int. J. Urol. 27, 702\u2013709. https:\/\/doi.org\/10.1111\/iju.14281 (2020).","journal-title":"Int. J. Urol."},{"key":"55917_CR15","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1097\/ju.0000000000003846","volume":"211","author":"JM Holzbeierlein","year":"2024","unstructured":"Holzbeierlein, J. M. et al. Diagnosis and treatment of non-muscle invasive bladder cancer: AUA\/SUO guideline: 2024 Amendment. J. Urol. 211, 533\u2013538. https:\/\/doi.org\/10.1097\/ju.0000000000003846 (2024).","journal-title":"J. Urol."},{"key":"55917_CR16","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1016\/S0022-5347(05)67707-5","volume":"163","author":"DL Lamm","year":"2000","unstructured":"Lamm, D. L. et al. Maintenance bacillus Calmette-Guerin immunotherapy for recurrent TA, T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized Southwest Oncology Group Study. J. Urol. 163, 1124\u20131129 (2000).","journal-title":"J. Urol."},{"key":"55917_CR17","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1093\/jjco\/hyt086","volume":"43","author":"J Miyazaki","year":"2013","unstructured":"Miyazaki, J. et al. Adverse reactions related to treatment compliance during BCG maintenance therapy for non-muscle-invasive bladder cancer. Jpn. J. Clin. Oncol. 43, 827\u2013834. https:\/\/doi.org\/10.1093\/jjco\/hyt086 (2013).","journal-title":"Jpn. J. Clin. Oncol."},{"key":"55917_CR18","doi-asserted-by":"publisher","first-page":"199","DOI":"10.5489\/cuaj.1196","volume":"3","author":"AR Zlotta","year":"2009","unstructured":"Zlotta, A. R., Fleshner, N. E. & Jewett, M. A. The management of BCG failure in non-muscle-invasive bladder cancer: an update. Can. Urol. Assoc. J. 3, 199\u2013205. https:\/\/doi.org\/10.5489\/cuaj.1196 (2009).","journal-title":"Can. Urol. Assoc. J."},{"issue":"5","key":"55917_CR19","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1016\/j.euo.2025.03.007","volume":"8","author":"M Longoni","year":"2025","unstructured":"Longoni, M. et al. Oncological outcomes in Bacillus Calmette-Gu\u00e9rin\u2013na\u00efve high-risk non\u2013muscle-invasive bladder cancer patients: A systematic review on current treatment strategies and future perspectives. Eur. Urol. Oncol. 8 (5), 1375\u20131392 (2025).","journal-title":"Eur. Urol. Oncol."},{"key":"55917_CR20","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1186\/s12894-023-01352-0","volume":"23","author":"J Tempo","year":"2023","unstructured":"Tempo, J., Bolton, D. & O\u2019Callaghan, M. Seminal papers in urology: maintenance Bacillus Calmette-Guerin (BCG) immunotherapy for recurrent Ta, T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized southwest oncology group study (SWOG-8507). BMC Urol. 23, 194. https:\/\/doi.org\/10.1186\/s12894-023-01352-0 (2023).","journal-title":"BMC Urol."},{"issue":"6","key":"55917_CR21","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.urolonc.2023.04.003","volume":"41","author":"T Kawada","year":"2023","unstructured":"Kawada, T. et al. The efficacy and safety outcomes of lower-dose BCG compared to intravesical chemotherapy in non\u2013muscle-invasive bladder cancer: A network meta-analysis. Urol. Oncol. 41 (6), 261\u2013273. https:\/\/doi.org\/10.1016\/j.urolonc.2023.04.003 (2023).","journal-title":"Urol. Oncol."},{"key":"55917_CR22","doi-asserted-by":"publisher","unstructured":"Sylvester, R. J. et al. Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur. Urol. 49, 466\u2013465. https:\/\/doi.org\/10.1016\/j.eururo.2005.12.031 (2006). (discussion 475\u2013467).","DOI":"10.1016\/j.eururo.2005.12.031"},{"key":"55917_CR23","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. et al. 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. Eur. Urol. 69, 60\u201369. https:\/\/doi.org\/10.1016\/j.eururo.2015.06.045 (2016).","journal-title":"Eur. Urol."},{"key":"55917_CR24","doi-asserted-by":"publisher","first-page":"2195","DOI":"10.1016\/j.juro.2009.07.016","volume":"182","author":"J Fernandez-Gomez","year":"2009","unstructured":"Fernandez-Gomez, J. et al. Predicting nonmuscle invasive bladder cancer recurrence and progression in patients treated with bacillus Calmette-Guerin: the CUETO scoring model. J. Urol. 182, 2195\u20132203. https:\/\/doi.org\/10.1016\/j.juro.2009.07.016 (2009).","journal-title":"J. Urol."},{"key":"55917_CR25","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1038\/s41597-021-00915-w","volume":"8","author":"D Vrabac","year":"2021","unstructured":"Vrabac, D. et al. DLBCL-Morph: Morphological features computed using deep learning for an annotated digital DLBCL image set. Sci. Data. 8, 135. https:\/\/doi.org\/10.1038\/s41597-021-00915-w (2021).","journal-title":"Sci. Data"},{"key":"55917_CR26","doi-asserted-by":"publisher","first-page":"101013","DOI":"10.1016\/j.xcrm.2023.101013","volume":"4","author":"V Nimgaonkar","year":"2023","unstructured":"Nimgaonkar, V. et al. Development of an artificial intelligence-derived histologic signature associated with adjuvant gemcitabine treatment outcomes in pancreatic cancer. Cell. Rep. Med. 4, 101013. https:\/\/doi.org\/10.1016\/j.xcrm.2023.101013 (2023).","journal-title":"Cell. Rep. Med."},{"key":"55917_CR27","unstructured":"MDV. Medical DataVision. https:\/\/en.mdv.co.jp\/ (accessed June 2025)."},{"key":"55917_CR28","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1093\/jjco\/hyae050","volume":"54","author":"S Okawa","year":"2024","unstructured":"Okawa, S. & Gatellier, L. Projection of the number of new cases of bladder cancer in the world. Jpn. J. Clin. Oncol. 54, 609\u2013610. https:\/\/doi.org\/10.1093\/jjco\/hyae050 (2024).","journal-title":"Jpn. J. Clin. Oncol."},{"key":"55917_CR29","unstructured":"MIMS Hong Kong. Immunobladder: Full Prescribing information., https:\/\/www.mims.com\/hongkong\/drug\/info\/immunobladder\/dosage. Accessed on June 2025."},{"key":"55917_CR30","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1159\/000527718","volume":"107","author":"T Tachibana","year":"2023","unstructured":"Tachibana, T. et al. Efficacy of intravesical instillation therapy with low-dose Tokyo-172 Bacillus Calmette-Gu\u00e9rin to prevent recurrence of non-muscle-invasive bladder cancer and treat carcinoma in situ: A multi-institutional retrospective study. Urol. Int. 107, 230\u2013238. https:\/\/doi.org\/10.1159\/000527718 (2023).","journal-title":"Urol. Int."},{"key":"55917_CR31","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1111\/iju.14933","volume":"29","author":"M Miyake","year":"2022","unstructured":"Miyake, M. et al. Real-world treatment patterns and clinical outcomes of Japanese patients with non-muscle invasive bladder cancer receiving intravesical bacillus Calmette-Gu\u00e9rin treatment. Int. J. Urol. 29, 1120\u20131129. https:\/\/doi.org\/10.1111\/iju.14933 (2022).","journal-title":"Int. J. Urol."},{"key":"55917_CR32","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.eururo.2021.08.010","volume":"81","author":"M Babjuk","year":"2022","unstructured":"Babjuk, M. et al. European association of urology guidelines on non-muscle-invasive bladder cancer (Ta, T1, and carcinoma in situ). Eur. Urol. 81, 75\u201394. https:\/\/doi.org\/10.1016\/j.eururo.2021.08.010 (2022).","journal-title":"Eur. Urol."},{"key":"55917_CR33","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1515\/almed-2021-0047","volume":"2","author":"AR Guerra Ruiz","year":"2021","unstructured":"Guerra Ruiz, A. R. et al. Measurement and clinical usefulness of bilirubin in liver disease. Adv. Lab. Med. 2, 352\u2013372. https:\/\/doi.org\/10.1515\/almed-2021-0047 (2021).","journal-title":"Adv. Lab. Med."},{"key":"55917_CR34","doi-asserted-by":"publisher","first-page":"020501","DOI":"10.11613\/bm.2025.020501","volume":"35","author":"I \u010cepelak","year":"2025","unstructured":"\u010cepelak, I., Dodig, S. & Pavi\u0107, I. Bilirubin\u2014new insights into an old molecule. Biochem. Med. (Zagreb). 35, 020501. https:\/\/doi.org\/10.11613\/bm.2025.020501 (2025).","journal-title":"Biochem. Med. (Zagreb)"},{"key":"55917_CR35","doi-asserted-by":"publisher","unstructured":"Ravindranathan, D., Master, V. A. & Bilen, M. A. Inflammatory markers in cancer immunotherapy. Biology (Basel). 10 https:\/\/doi.org\/10.3390\/biology10040325 (2021).","DOI":"10.3390\/biology10040325"},{"key":"55917_CR36","doi-asserted-by":"publisher","unstructured":"Thompson, L. E. & Joy, M. S. Endogenous markers of kidney function and renal drug clearance processes of filtration, secretion, and reabsorption. Curr. Opin. Toxicol. 31 https:\/\/doi.org\/10.1016\/j.cotox.2022.03.005 (2022).","DOI":"10.1016\/j.cotox.2022.03.005"},{"key":"55917_CR37","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/s41585-024-00914-7","volume":"22","author":"M Olislagers","year":"2025","unstructured":"Olislagers, M. et al. Molecular biomarkers of progression in non-muscle-invasive bladder cancer\u2014beyond conventional risk stratification. Nat. Rev. Urol. 22, 75\u201391. https:\/\/doi.org\/10.1038\/s41585-024-00914-7 (2025).","journal-title":"Nat. Rev. Urol."},{"key":"55917_CR38","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1038\/s41698-024-00725-4","volume":"8","author":"QD Xia","year":"2024","unstructured":"Xia, Q. D. et al. The role of TERT C228T and KDM6A alterations and TME in NMIBC treated with BCG. NPJ Precis. Oncol. 8, 216. https:\/\/doi.org\/10.1038\/s41698-024-00725-4 (2024).","journal-title":"NPJ Precis. Oncol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-55917-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-55917-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-55917-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T13:04:46Z","timestamp":1786539886000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-55917-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,2]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["55917"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-55917-8","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,2]]},"assertion":[{"value":"18 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All authors except H.K. and P.A. are employees of Ferring Pharmaceuticals or were at the time of the study. P.P. is CEO and shareholder of Shiroito Co. Ltd, is a member of PharmaBiome Board of Directors and owns stocks in Takeda Pharmaceutical Co., Ltd. H. K. serves as a consultant for Ferring Pharmaceuticals and receives consulting fees. A.N. is a shareholder of GlaxoSmithKline. P.A. is an employee of Medical Data Vision Co., Ltd.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"25051"}}