{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T01:15:32Z","timestamp":1788311732183,"version":"build-2803163510"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Trimodality therapy (TMT), including transurethral resection (TUR), chemotherapy (CT), and radiotherapy (RT), offers the bladder-preserving treatment option for patients with muscle-invasive bladder cancer (MIBC). TMT, once indicated, has demonstrated effective and favorable local tumor control in MIBC, with complete response rates ranging between 50% and 80%. However, residual tumor is identified on follow-up TUR in approximately 20\u201330% of patients, and tumor recurrence occurs in a similar proportion. In both situations, the prognosis becomes unfavorable. This manuscript reviews the current evidence regarding recurrence patterns after TMT, differentiating between non\u2013muscle-invasive (NMIBC) and muscle-invasive (MIBC) relapses. NMIBC recurrences after TMT are often manageable with conservative treatments like repeat TURBT and intravesical BCG, without negatively impacting survival. In contrast, MIBC recurrences typically require salvage cystectomy in fit patients, offering outcomes similar to primary surgery. For those unfit for or who continue to decline cystectomy, treatment remains uncertain due to the absence of clear guidelines, and systemic therapies used in metastatic urothelial carcinoma seem commonly applied by extrapolation.<\/jats:p>","DOI":"10.3389\/fonc.2025.1672431","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T04:16:57Z","timestamp":1759292217000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Management of bladder cancer recurrence following the trimodality therapy"],"prefix":"10.3389","volume":"15","author":[{"given":"Nahed","family":"Damaj","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabih","family":"Naim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Saad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarisse","family":"Kattan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Kattan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,1]]},"reference":[{"key":"B1","article-title":"Key statistics for bladder cancer","volume-title":"Bladder cancer in Lebanon: Incidence and Comparison to Regional and Western Countries","year":"2023"},{"key":"B2","doi-asserted-by":"publisher","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":"B3","first-page":"81","article-title":"International agency for research on cancer. 4th edition ed. Lyon, France: infiltrating urothelial carcinoma; (2016)","volume-title":"WHO classification of tumours of the urinary system and male genital organs","author":"Moch","year":""},{"key":"B4","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.eururo.2012.08.009","article-title":"ICUD-EAU international consultation on bladder cancer 2012: Radical cystectomy and bladder preservation for muscle-invasive urothelial carcinoma of the bladder","volume":"63","author":"Gakis","year":"2013","journal-title":"Eur Urol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2025.1543837","article-title":"The practical roadmap for peri-cystectomy approaches in muscle-invasive bladder cancer","volume":"15","author":"Kattan","year":"2025","journal-title":"Front Oncol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1016\/j.juro.2006.03.038","article-title":"Cystectomy for transitional cell carcinoma of the bladder: results of a surgery only series in the neobladder era","volume":"176","author":"Hautmann","year":"2006","journal-title":"J Urol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2011.1142","article-title":"Association between smoking and risk of bladder cancer among men and women","volume":"306","author":"Freedman","year":"2011","journal-title":"JAMA"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2004.05.074","article-title":"Phase I study of conformal radiotherapy with concurrent gemcitabine in locally advanced bladder cancer","volume":"61","author":"Sangar","year":"2005","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-4295(02)01650-3","article-title":"Selective bladder preservation by combined modality protocol treatment: long-term outcomes of 190 patients with invasive bladder cancer","volume":"60","author":"Shipley","year":"2002","journal-title":"Urology"},{"key":"B10","author":"Solakhan","year":"2021"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2017.08.106","article-title":"Incidence, clinicopathological risk factors, management and outcomes of nonmuscle invasive recurrence after complete response to trimodality therapy for muscle invasive bladder cancer","volume":"199","author":"Sanchez","year":"2018","journal-title":"J Urol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2018.07.058","article-title":"Long-term outcomes and patterns of failure following trimodality treatment with bladder preservation for invasive bladder cancer","volume":"124","author":"B\u00fcchser","year":"2019","journal-title":"Urology"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgo.2022.05.014","article-title":"Bladder preservation in older adults with muscle-invasive bladder cancer: a retrospective study with concurrent chemotherapy and twice-daily hypofractionated radiotherapy schedule","volume":"13","author":"Alati","year":"2022","journal-title":"J Geriatr Oncol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1080\/0284186x.2021.1915498","article-title":"Long-term outcomes after bladder-preserving tri-modality therapy for patients with muscle-invasive bladder cancer","volume":"60","author":"Fabiano","year":"2021","journal-title":"Acta Oncol (Stockholm Sweden)"},{"key":"B15","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1016\/j.urolonc.2021.05.008","article-title":"Characterization and management of NMIBC recurrences after TMT: a matched cohort analysis","volume":"39","author":"Ajib","year":"2021","journal-title":"Urol Oncol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e298","DOI":"10.1016\/j.juro.2015.02.1134","article-title":"Incidence and management of non-muscle invasive bladder cancer recurrences after complete response to combined-modality organ-preserving therapy for muscle invasive bladder cancer","volume":"193","author":"Sanchez","year":"2015","journal-title":"J Urol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/j.juro.2011.09.159","article-title":"Complications and long-term results of salvage cystectomy after failed bladder sparing therapy for muscle invasive bladder cancer","volume":"187","author":"Eswara","year":"2012","journal-title":"J Urol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1016\/j.eururo.2009.12.002","article-title":"Differential complication rates following radical cystectomy in the irradiated and nonirradiated pelvis","volume":"57","author":"Ramani","year":"2010","journal-title":"Eur Urol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1097\/JU.0000000000001696","article-title":"Complications and outcomes of salvage cystectomy after trimodality therapy","volume":"206","author":"Pieretti","year":"2021","journal-title":"J Urol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2002.11.027","article-title":"Combined-modality treatment and selective organ preservation in invasive bladder cancer: long-term results","volume":"20","author":"R\u00f6del","year":"2002","journal-title":"J Clin Oncol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1177\/1179064418761639","article-title":"The impact of radiation on the tumor microenvironment: effect of dose and fractionation schedules","volume":"11","author":"Arnold","year":"2018","journal-title":"Cancer Growth Metastasis"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-1758","article-title":"Molecular pathways: emerging pathways mediating growth, invasion, and metastasis of tumors progressing in an irradiated microenvironment","volume":"18","author":"Kuonen","year":"2012","journal-title":"Clin Cancer Res"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2012.11476.x","article-title":"Management of local recurrences in the irradiated bladder: a systematic review","author":"Sapre","year":"2012","journal-title":"BJU Int"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2025.1562260","article-title":"Advances in bladder preservation therapy for muscle-invasive bladder cancer","volume":"15","author":"Zhang","year":"2025","journal-title":"Front Oncol"},{"key":"B25","doi-asserted-by":"crossref","DOI":"10.1111\/j.1464-410X.2012.11476.x","article-title":"Management of local recurrences in the irradiated bladder: a systematic review","volume":"110","author":"Sapre","year":"2012","journal-title":"BJU International"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1672431\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T04:16:58Z","timestamp":1759292218000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1672431\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,1]]},"references-count":25,"alternative-id":["10.3389\/fonc.2025.1672431"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2025.1672431","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,1]]},"article-number":"1672431"}}