{"entity":{"id":"muscle-invasive-bladder-cancer","kind":"cancer","name":"Muscle-invasive and advanced bladder cancer","aka":["MIBC","Invasive urothelial carcinoma","Metastatic urothelial carcinoma"],"tldr":"Once bladder cancer has grown into the muscle it needs more than scraping out: chemotherapy then removal of the bladder, or chemoradiation to keep it. For cancer that has spread, the antibody-drug conjugate enfortumab vedotin with pembrolizumab has replaced platinum chemotherapy as the first treatment.","summary":"Muscle-invasive urothelial carcinoma is treated with cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy and urinary diversion, or by trimodality bladder preservation (maximal resection plus chemoradiation) in suitable patients. Perioperative immunotherapy has entered practice: adjuvant nivolumab after cystectomy (CheckMate 274) and durvalumab with neoadjuvant chemotherapy and after surgery (NIAGARA), which improved overall survival. For metastatic disease, enfortumab vedotin with pembrolizumab nearly doubled survival compared with platinum chemotherapy (EV-302) and became the standard first-line treatment in 2023; erdafitinib is used for FGFR3-altered tumours, and platinum chemotherapy followed by avelumab maintenance remains an option. Molecular subtypes (luminal, basal) and circulating tumour DNA are being used to select who needs adjuvant treatment.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Bladder_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Bladder_cancer"}],"tags":["subtype-page"],"related":["non-muscle-invasive-bladder-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-niagara-nejm-2024","paper-ev-302-nejm-2024","paper-swog-8710-neoadjuvant-mvac-nejm-2003","paper-javelin-bladder-100-nejm-2020"],"journals":[],"dependsOn":[],"notes":[],"group":"genitourinary","burden":"About a quarter of bladder cancers at diagnosis plus those that progress from superficial disease; half of patients with muscle invasion die of it within five years despite surgery, and metastatic disease had a median survival near a year until antibody-drug conjugates and immunotherapy changed it.","subtypes":["Muscle-invasive, organ-confined (T2)","Locally advanced (T3 to T4, node-positive)","Metastatic urothelial carcinoma","FGFR3-altered urothelial carcinoma","Variant histologies (squamous, small cell, plasmacytoid, micropapillary)"],"biomarkers":["Cisplatin eligibility (kidney function, hearing, performance status)","PD-L1 expression (selects immunotherapy in some settings)","FGFR3 mutations and fusions (erdafitinib)","Nectin-4 expression (near universal; enfortumab vedotin target)","Circulating tumour DNA after cystectomy (adjuvant selection)"],"standardOfCare":[{"setting":"Muscle-invasive, cisplatin-eligible","approach":"Neoadjuvant cisplatin-based chemotherapy (dose-dense MVAC or gemcitabine-cisplatin) with durvalumab (NIAGARA), then radical cystectomy with lymph node dissection and adjuvant durvalumab; adjuvant nivolumab for high-risk residual disease (CheckMate 274).","refs":["cisplatin","gemcitabine","durvalumab","niagara","cystectomy","nivolumab","checkmate-274"]},{"setting":"Bladder preservation","approach":"Maximal transurethral resection followed by chemoradiation, with salvage cystectomy for recurrence, in patients with unifocal tumours and no carcinoma in situ or in those unfit for surgery.","refs":["imrt-igrt","radiosensitisers","cisplatin"]},{"setting":"Metastatic, first line","approach":"Enfortumab vedotin plus pembrolizumab (EV-302); gemcitabine-platinum followed by avelumab maintenance where the combination is unavailable.","refs":["enfortumab-vedotin","pembrolizumab","ev-302"]},{"setting":"Later lines","approach":"Erdafitinib for FGFR3 alterations; platinum chemotherapy or enfortumab vedotin if not given first line; clinical trials.","refs":["erdafitinib","fgfr3-receptor","enfortumab-vedotin"]}],"stateOfArt":["EV-302 was the first trial in forty years to beat platinum chemotherapy first line, and it did so by a wide margin.","Perioperative immunotherapy now improves survival around cystectomy, and circulating tumour DNA promises to select who needs it.","Bladder preservation with chemoradiation gives survival similar to cystectomy in selected patients and is under-used."],"history":[{"year":1985,"title":"MVAC chemotherapy established for advanced disease","refs":["cisplatin"]},{"year":2003,"title":"Neoadjuvant MVAC improves survival before cystectomy (SWOG 8710)","refs":["cisplatin"]},{"year":2016,"title":"Atezolizumab: first immunotherapy approval in bladder cancer","refs":[]},{"year":2019,"title":"Erdafitinib: first targeted drug for FGFR3-altered urothelial cancer","refs":["erdafitinib"]},{"year":2021,"title":"Adjuvant nivolumab (CheckMate 274)","refs":["checkmate-274"]},{"year":2023,"title":"EV-302: enfortumab vedotin plus pembrolizumab replaces platinum first line","refs":["ev-302"]},{"year":2024,"title":"NIAGARA: perioperative durvalumab improves survival","refs":["niagara"]}],"pipeline":["durvalumab","erdafitinib","enfortumab-vedotin"],"openProblems":["Cisplatin-ineligible patients still have fewer options.","Choosing between cystectomy and bladder preservation lacks randomised evidence.","Variant histologies are excluded from most trials.","Cost and access to antibody-drug conjugates."],"parent":"urothelial"},"route":"/cancers/muscle-invasive-bladder-cancer/","neighbours":{"cancer":[{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"non-muscle-invasive-bladder-cancer","kind":"cancer","name":"Non-muscle-invasive bladder cancer","route":"/cancers/non-muscle-invasive-bladder-cancer/"}],"paper":[{"id":"paper-ev-302-nejm-2024","kind":"paper","name":"EV-302: enfortumab vedotin plus pembrolizumab replaces chemotherapy as first treatment for advanced bladder cancer","route":"/key-papers/paper-ev-302-nejm-2024/"},{"id":"paper-javelin-bladder-100-nejm-2020","kind":"paper","name":"JAVELIN Bladder 100: avelumab maintenance after first-line platinum chemotherapy in advanced urothelial cancer","route":"/key-papers/paper-javelin-bladder-100-nejm-2020/"},{"id":"paper-niagara-nejm-2024","kind":"paper","name":"NIAGARA: durvalumab before and after cystectomy for muscle-invasive bladder cancer","route":"/key-papers/paper-niagara-nejm-2024/"},{"id":"paper-swog-8710-neoadjuvant-mvac-nejm-2003","kind":"paper","name":"SWOG 8710: neoadjuvant MVAC chemotherapy before cystectomy for muscle-invasive bladder cancer","route":"/key-papers/paper-swog-8710-neoadjuvant-mvac-nejm-2003/"}],"drug":[{"id":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"},{"id":"enfortumab-vedotin","kind":"drug","name":"Enfortumab vedotin","route":"/drugs/enfortumab-vedotin/"},{"id":"erdafitinib","kind":"drug","name":"Erdafitinib","route":"/drugs/erdafitinib/"},{"id":"gemcitabine","kind":"drug","name":"Gemcitabine","route":"/drugs/gemcitabine/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"trial":[{"id":"nct06823427","kind":"trial","name":"9MW2821 + Toripalimab vs 9MW2821 for 1st Line Locally Advanced or Metastatic Urothelial Carcinoma","route":"/trials/nct06823427/"},{"id":"nct06079112","kind":"trial","name":"9MW2821 Combined With Toripalimab Injection in Subjects With Local Advanced or Metastatic Urothelial Cancer","route":"/trials/nct06079112/"},{"id":"nct06592326","kind":"trial","name":"9MW2821 in Combination With Toripalimab vs Standard Chemotherapy in Locally Advanced or Metastatic Urothelial Cancer","route":"/trials/nct06592326/"},{"id":"nct06305767","kind":"trial","name":"A Clinical Study of Intismeran Autogene (V940) Treatment and Pembrolizumab in People With Bladder Cancer (V940-005/INTerpath-005)","route":"/trials/nct06305767/"},{"id":"nct07419295","kind":"trial","name":"A Clinical Trial of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) to Treat Urothelial Cancer (MK-2870-031)","route":"/trials/nct07419295/"},{"id":"nct06857175","kind":"trial","name":"A Study Comparing BL-B01D1 With Chemotherapy of Physician's Choice in Patients With Recurrent or Metastatic Urothelial Carcinoma(PANKU-Bladder01)","route":"/trials/nct06857175/"},{"id":"nct05645692","kind":"trial","name":"A Study Evaluating Different Immunotherapies (LAG-3 and PD-1 With or Without TIGIT, Compared to PD-L1 Alone) in Participants With Untreated Locally Advanced Metastatic Urothelial Cancer","route":"/trials/nct05645692/"},{"id":"nct06405425","kind":"trial","name":"A Study of BL-B01D1 + PD-1 in Patients With Locally Advanced or Metastatic Urothelial Carcinoma","route":"/trials/nct06405425/"},{"id":"nct04879329","kind":"trial","name":"A Study of Disitamab Vedotin Alone or With Pembrolizumab in Urothelial Cancer That Expresses HER2","route":"/trials/nct04879329/"},{"id":"nct03459846","kind":"trial","name":"A Study of Durvalumab Alone and Durvalumab+Olaparib in Advanced, Platinum-Ineligible Bladder Cancer (BAYOU)","route":"/trials/nct03459846/"},{"id":"nct05845814","kind":"trial","name":"A Study of Efficacy and Safety of Pembrolizumab Plus Enfortumab Vedotin (EV) +/- Investigational Agents in First-Line Metastatic Urothelial Carcinoma (mUC) (MK-3475-04B/KEYMAKER-U04)","route":"/trials/nct05845814/"},{"id":"nct06483334","kind":"trial","name":"A Study of Efficacy and Safety of Sacituzumab Tirumotecan (MK-2870) Plus Enfortumab Vedotin (EV) With and Without Pembrolizumab in Advanced Urothelial Carcinoma (MK-3475-04C/KEYMAKER-U04)","route":"/trials/nct06483334/"},{"id":"nct03473743","kind":"trial","name":"A Study of Erdafitinib in 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of TAR-200 in Combination With Cetrelimab Versus Concurrent Chemoradiotherapy in Participants With Muscle-invasive Bladder Cancer (MIBC) of the Bladder","route":"/trials/nct04658862/"},{"id":"nct05327530","kind":"trial","name":"A Study of the Safety and Efficacy of Various Combinations of Avelumab as Therapy in Locally Advanced or Metastatic Urothelial Carcinoma (JAVELIN Bladder Medley)","route":"/trials/nct05327530/"},{"id":"nct07218380","kind":"trial","name":"A Study of Vepugratinib (LY3866288) in Participants With Cancer in the Urinary Tract","route":"/trials/nct07218380/"},{"id":"nct06196736","kind":"trial","name":"A Study to Evaluate 9MW2821 Versus Chemotherapy in Subjects With Previously Treated Locally Advanced or Metastatic Urothelial Cancer","route":"/trials/nct06196736/"},{"id":"nct07475806","kind":"trial","name":"A Study to Find Out if Enfortumab Vedotin Given With Pembrolizumab Helps People With Muscle-invasive Bladder Cancer Keep Their 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(MK-3475-992/KEYNOTE-992)","route":"/trials/nct04241185/"},{"id":"nct07566156","kind":"trial","name":"Enfortumab Vedotin in Combination With Pembrolizumab vs. Concurrent Chemoradiotherapy (cCRT) in People With Muscle Invasive Bladder Cancer (EV-309)","route":"/trials/nct07566156/"},{"id":"ev-302","kind":"trial","name":"EV-302 / KEYNOTE-A39","route":"/trials/ev-302/"},{"id":"nct07232602","kind":"trial","name":"KEYMAKER-U04 Substudy 04D: A Clinical Study of New Treatments Given With Enfortumab Vedotin and Pembrolizumab in People With Urothelial Cancer (MK-3475-04D/KEYMAKER-U04)","route":"/trials/nct07232602/"},{"id":"niagara","kind":"trial","name":"NIAGARA","route":"/trials/niagara/"},{"id":"nct06960577","kind":"trial","name":"Perioperative Durvalumab With Neoadjuvant ddMVAC or Gemcitabine/Cisplatin in Patients With Muscle-invasive Bladder Cancer (NIAGARA-2)","route":"/trials/nct06960577/"},{"id":"nct07106762","kind":"trial","name":"Phase 2/3 Trial of Izalontamab Brengitecan vs 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Events and Change in Disease Activity When Intravenously (IV) Infused Livmoniplimab is Used in Combination With IV Infused Budigalimab in Adult Participants With Urothelial Carcinoma (UC)","route":"/trials/nct06632951/"},{"id":"nct07421700","kind":"trial","name":"Symbiotic-GU-06: A Study to Learn About PF-08634404 Alone or In Combination With Enfortumab Vedotin in Urothelial Cancer","route":"/trials/nct07421700/"},{"id":"nct04960709","kind":"trial","name":"Treatment Combination of Durvalumab, Tremelimumab and Enfortumab Vedotin or Durvalumab and Enfortumab Vedotin in Patients With Muscle Invasive Bladder Cancer Ineligible to Cisplatin or Who Refuse Cisplatin","route":"/trials/nct04960709/"}],"term":[{"id":"cystectomy","kind":"term","name":"Radical cystectomy","route":"/terms/cystectomy/"}],"technology":[{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"radiosensitisers","kind":"technology","name":"Radiosensitisers","route":"/technologies/radiosensitisers/"},{"id":"ring-gantry-linac","kind":"technology","name":"Ring-gantry linacs (Halcyon, Ethos)","route":"/technologies/ring-gantry-linac/"},{"id":"surgical-robot-platforms","kind":"technology","name":"Surgical robots: da Vinci, Hugo, Versius and single-port systems","route":"/technologies/surgical-robot-platforms/"},{"id":"urine-bladder-cancer-tests","kind":"technology","name":"Urine tests for bladder cancer (cytology, FISH, RNA and methylation)","route":"/technologies/urine-bladder-cancer-tests/"}],"target":[{"id":"fgfr3-receptor","kind":"target","name":"FGFR3","route":"/targets/fgfr3-receptor/"}]}}