Skip to content
2000
Volume 26, Issue 13
  • ISSN: 1389-4501
  • E-ISSN: 1873-5592

Abstract

Numerous bladder-related diseases, including urinary blockages, interstitial cystitis, overactive bladder syndrome, cancer, and infections of the urinary tract, can affect bladder function. The human urinary bladder's distinct anatomy successfully prevents any hazardous material from entering circulation. The pathogenesis was assessed according to the extent of invasion in the bladder wall tissue obtained through Transurethral Resection of Bladder Tumor (TURBT) and classified as Muscle-Invasive and Non-Muscle Invasive Bladder Cancer (MBIC and NMIBC). Intravesical Drug Delivery (IDD) has recently gained attention for treating bladder disorders. IDD refers to the insertion of a drug directly into the bladder using a catheter. Intravesical administration of immunotherapy or chemotherapy has been demonstrated to reduce recurrence rates and inhibit disease progression. In addition, several other systems, including recombinant BCG, gene therapy, vectors, and Antibody-Drug Conjugates (ADCs), are now used. Moreover, the novel intravesical formulations of distinct chemotherapeutic agents, including gemcitabine, Doxorubicin (DOX), and Mitomycin C (MMC), are used in bladder-related problems. Novel intravesical drugs, polymeric hydrogels, dendrimers, hydrogels, mucoadhesives, nanocarriers, and intravesical devices have been discussed. Aside from chemotherapy and immunotherapy, devices such as GemRIS, device-assisted hyperthermic intravesical chemotherapy, and photodynamic therapy are utilized.

Loading

Article metrics loading...

/content/journals/cdt/10.2174/0113894501384020250804093144
2025-08-06
2026-01-26
Loading full text...

Full text loading...

References

  1. LealJ. Luengo-FernandezR. SullivanR. WitjesJ.A. Economic burden of bladder cancer across the European union.Eur. Urol.201669343844710.1016/j.eururo.2015.10.02426508308
    [Google Scholar]
  2. RovnerE.S. WeinA.J. Once-daily, extended-release formulations of antimuscarinic agents in the treatment of overactive bladder: A review.Eur. Urol.200241161410.1016/S0302‑2838(01)00009‑411999467
    [Google Scholar]
  3. de BruijnE.A. SleeboomH.P. van HelsdingenP.J.R.O. van OosteromA.T. TjadenU.R. MaesR.A.A. Pharmacodynamics and pharmacokinetics of intravesical mitomycin C upon different dwelling times.Int. J. Cancer199251335936410.1002/ijc.29105103051592527
    [Google Scholar]
  4. TyagiP. WuP.C. ChancellorM. YoshimuraN. HuangL. Recent advances in intravesical drug/gene delivery.Mol. Pharm.20063436937910.1021/mp060001j16889430
    [Google Scholar]
  5. LewisS.A. Everything you wanted to know about the bladder epithelium but were afraid to ask.Am. J. Physiol. Renal Physiol.20002786F867F87410.1152/ajprenal.2000.278.6.F86710836974
    [Google Scholar]
  6. PoggiM.M. JohnstoneP.A.S. ConnerR.J. Glycosaminoglycan content of human bladders.Urol. Oncol.20005523423710.1016/S1078‑1439(00)00074‑010973714
    [Google Scholar]
  7. SvensonS. Dendrimers as versatile platform in drug delivery applications.Eur. J. Pharm. Biopharm.200971344546210.1016/j.ejpb.2008.09.02318976707
    [Google Scholar]
  8. IrwinD.E. KoppZ.S. AgatepB. MilsomI. AbramsP. Worldwide prevalence estimates of lower urinary tract symptoms, overactive bladder, urinary incontinence and bladder outlet obstruction.BJU Int.201110871132113810.1111/j.1464‑410X.2010.09993.x21231991
    [Google Scholar]
  9. YamadaY. SatoY. NakamuraT. HarashimaH. Evolution of drug delivery system from viewpoint of controlled intracellular trafficking and selective tissue targeting toward future nanomedicine.J. Control. Release202032753354510.1016/j.jconrel.2020.09.00732916227
    [Google Scholar]
  10. ColombelM. SolowayM. AkazaH. BöhleA. PalouJ. BuckleyR. LammD. BrausiM. WitjesJ.A. PersadR. Epidemiology, staging, grading, and risk stratification of bladder cancer.Eur. Urol. Suppl.200871061862610.1016/j.eursup.2008.08.002
    [Google Scholar]
  11. LiuC.W. WuY.T. LinK.J. YuT.J. KuoY.L. ChangL.C. A hydrogel-based epirubicin delivery system for intravesical chemotherapy.Molecules201621671210.3390/molecules2106071227258243
    [Google Scholar]
  12. ParkinJ SheaC SantGR Intravesical dimethyl sulfoxide (DMSO) for interstitial cystitis—A practical approach.Urology1997495A Suppl10510710.1016/s0090‑4295(97)00181‑79146010
    [Google Scholar]
  13. ZargarH. AningJ. IschiaJ. SoA. BlackP. Optimizing intravesical mitomycin C therapy in non-muscle-invasive bladder cancer.Nat. Rev. Urol.201411422023010.1038/nrurol.2014.5224619373
    [Google Scholar]
  14. KuoH.C. LiuH.T. ChuangY.C. BirderL.A. ChancellorM.B. Pilot study of liposome-encapsulated onabotulinumtoxina for patients with overactive bladder: A single-center study.Eur. Urol.20146561117112410.1016/j.eururo.2014.01.03624555904
    [Google Scholar]
  15. RajaganapathyB.R. JayabalanN. TyagiP. KaufmanJ. ChancellorM.B. Advances in therapeutic development for radiation cystitis.Low. Urin. Tract Symptoms20146111010.1111/luts.1204526663493
    [Google Scholar]
  16. TyagiP. KashyapM.P. KawamoritaN. YoshizawaT. ChancellorM. YoshimuraN. Intravesical liposome and antisense treatment for detrusor overactivity and interstitial cystitis/painful bladder syndrome.ISRN Pharmacol.2014201411210.1155/2014/60165324527221
    [Google Scholar]
  17. HolzbeierleinJ.M. BixlerB.R. BuckleyD.I. ChangS.S. HolmesR. JamesA.C. KirkbyE. McKiernanJ.M. SchuckmanA.K. Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO Guideline: 2024 amendment.J. Urol.2024211453353810.1097/JU.000000000000384638265030
    [Google Scholar]
  18. QuF. DarjiS. ThompsonD.H. Recent advances in drug delivery strategies for high-risk BCG-unresponsive non-muscle invasive bladder cancer: A brief review from 2018 to 2024.Pharmaceutics2024169115410.3390/pharmaceutics1609115439339191
    [Google Scholar]
  19. DyrskjøtL. HanselD.E. EfstathiouJ.A. KnowlesM.A. GalskyM.D. TeohJ. TheodorescuD. Bladder cancer.Nat. Rev. Dis. Primers2023915810.1038/s41572‑023‑00468‑937884563
    [Google Scholar]
  20. ChangS.S. BoorjianS.A. ChouR. ClarkP.E. DaneshmandS. KonetyB.R. PruthiR. QualeD.Z. RitchC.R. SeigneJ.D. SkinnerE.C. SmithN.D. McKiernanJ.M. Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO guideline.J. Urol.201619641021102910.1016/j.juro.2016.06.04927317986
    [Google Scholar]
  21. FlaigT.W. SpiessP.E. AbernM. AgarwalN. BangsR. BoorjianS.A. BuyyounouskiM.K. ChanK. ChangS. FriedlanderT. GreenbergR.E. GuruK.A. HerrH.W. Hoffman-CensitsJ. KishanA. KunduS. LeleS.M. MamtaniR. MargulisV. MianO.Y. MichalskiJ. MontgomeryJ.S. NandagopalL. PagliaroL.C. ParikhM. PattersonA. PlimackE.R. PoharK.S. PrestonM.A. RichardsK. SextonW.J. Siefker-RadtkeA.O. TollefsonM. TwardJ. WrightJ.L. DwyerM.A. CassaraC.J. GurskiL.A. NCCN Guidelines® Insights: Bladder Cancer, Version 2.2022.J. Natl. Compr. Canc. Netw.202220886687810.6004/jnccn.2022.004135948037
    [Google Scholar]
  22. PackiamV.T. WerntzR.P. SteinbergG.D. Current clinical trials in non-muscle-invasive bladder cancer: Heightened need in an era of chronic BCG shortage.Curr. Urol. Rep.201920128410.1007/s11934‑019‑0952‑y31781942
    [Google Scholar]
  23. PatelS.G. CohenA. WeinerA.B. SteinbergG.D. Intravesical therapy for bladder cancer.Expert Opin. Pharmacother.201516688990110.1517/14656566.2015.102465625773220
    [Google Scholar]
  24. ShinJ. ParkJ. KimS. LeeJ. ChoiW. KimH. Strategies for overcoming immune evasion in bladder cancer.Int. J. Mol. Sci.2024256310510.3390/ijms2506310538542078
    [Google Scholar]
  25. BabjukM. BurgerM. CapounO. CohenD. CompératE.M. Dominguez EscrigJ.L. GonteroP. LiedbergF. Masson-LecomteA. MostafidA.H. PalouJ. van RhijnB.W.G. RouprêtM. ShariatS.F. SeisenT. SoukupV. SylvesterR.J. European association of urology guidelines on non–muscle-invasive bladder cancer (Ta, T1, and Carcinoma in situ).Eur. Urol.2022811759410.1016/j.eururo.2021.08.01034511303
    [Google Scholar]
  26. AudisioA. ButtiglieroC. DelcuratoloM.D. ParlagrecoE. AudisioM. UngaroA. Di StefanoR.F. Di PrimaL. TurcoF. TucciM. New perspectives in the medical treatment of non-muscle-invasive bladder cancer: Immune checkpoint inhibitors and beyond.Cells202211335710.3390/cells1103035735159167
    [Google Scholar]
  27. ChoiH. JeongS. SimóC. BakeneckerA. LiopJ. LeeH.S. KimT.Y. KwakC. KohG.Y. SánchezS. HahnS.K. Urease-powered nanomotor containing STING agonist for bladder cancer immunotherapy.Nat. Commun.2024151993410.1038/s41467‑024‑54293‑z39548120
    [Google Scholar]
  28. FragkoulisC. GlykasI. BamiasA. StathourosG. PapadopoulosG. NtoumasK. Novel treatments in BCG failure. Where do we stand today?Arch. Esp. Urol.202174768169134472437
    [Google Scholar]
  29. TorchilinV.P. Drug targeting.Eur. J. Pharm. Sci.200011Suppl. 2S81S9110.1016/S0928‑0987(00)00166‑411033430
    [Google Scholar]
  30. JiangS. Redelman-SidiG. BCG in bladder cancer immunotherapy.Cancers20221413307310.3390/cancers1413307335804844
    [Google Scholar]
  31. TempoJ. BoltonD. O’CallaghanM. 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.202323119410.1186/s12894‑023‑01352‑037996890
    [Google Scholar]
  32. Abou ChakraM. LuoY. DuquesneI. A O’DonnellM. Update on the mechanism of action of intravesical BCG therapy to treat non-muscle-invasive bladder cancer.Front. Biosci.202429829510.31083/j.fbl290829539206898
    [Google Scholar]
  33. YuD.S. WuC.L. PingS.Y. KengC. ShenK.H. Bacille Calmette-Guerin can induce cellular apoptosis of urothelial cancer directly through toll-like receptor 7 activation.Kaohsiung J. Med. Sci.201531839139710.1016/j.kjms.2015.05.00526228277
    [Google Scholar]
  34. MiyakawaJ. YamadaY. HakozakiY. MakinoK. KameiJ. TaguchiS. KawaiT. AkiyamaY. YamadaD. KumeH. Comparison of PDD-TURBT alone versus white light TURBT plus intravesical BCG therapy: A propensity-score matching study.Photodiagn. Photodyn. Ther.20244810425410.1016/j.pdpdt.2024.10425438901718
    [Google Scholar]
  35. GallegosH. RojasP.A. SepúlvedaF. ZúñigaÁ. San FranciscoI.F. Protective role of intravesical BCG in COVID-19 severity.BMC Urol.20212115010.1186/s12894‑021‑00823‑633785004
    [Google Scholar]
  36. van PuffelenJ.H. NovakovicB. van EmstL. KooperD. ZuiverloonT.C.M. OldenhofU.T.H. WitjesJ.A. GaleslootT.E. VrielingA. AbenK.K.H. KiemeneyL.A.L.M. OosterwijkE. NeteaM.G. BoormansJ.L. van der HeijdenA.G. JoostenL.A.B. VermeulenS.H. Intravesical BCG in patients with non-muscle invasive bladder cancer induces trained immunity and decreases respiratory infections.J. Immunother. Cancer202311100551810.1136/jitc‑2022‑00551836693678
    [Google Scholar]
  37. ZengS. XingS. ZhangY. WangH. LiuQ. Nano-Bacillus Calmette-Guérin immunotherapies for improved bladder cancer treatment.J. Zhejiang Univ. Sci. B202425755756710.1631/jzus.B230039239011676
    [Google Scholar]
  38. GonzalezO.Y. MusherD.M. BrarI. FurgesonS. BoktourM.R. SeptimusE.J. HamillR.J. GravissE.A. Spectrum of bacille Calmette-Guérin (BCG) infection after intravesical BCG immunotherapy.Clin. Infect. Dis.200336214014810.1086/34490812522745
    [Google Scholar]
  39. KochG.E. SmelserW.W. ChangS.S. Side effects of intravesical bcg and chemotherapy for bladder cancer: What they are and how to manage them.Urology2021149112010.1016/j.urology.2020.10.03933181123
    [Google Scholar]
  40. Gual FrauJ. PalouJ. RodríguezO. ParadaR. BredaA. VillavicencioH. Failure of Bacillus Calmette-Guérin therapy in non-muscle-invasive bladder cancer: Definition and treatment options.Arch. Esp. Urol.201669742343327617552
    [Google Scholar]
  41. PengY. SongY. QinC. DuY. XuT. Safety profiles of intravesical Bacillus Calmette-Guerin in bladder cancer.Hum. Vaccin. Immunother.2024201242552910.1080/21645515.2024.242552939539079
    [Google Scholar]
  42. ZhangL. GuF.X. ChanJ.M. WangA.Z. LangerR.S. FarokhzadO.C. Nanoparticles in medicine: Therapeutic applications and developments.Clin. Pharmacol. Ther.200883576176910.1038/sj.clpt.610040017957183
    [Google Scholar]
  43. KatesM. MatosoA. ChoiW. BarasA.S. DanielsM.J. LombardoK. BrantA. MikkilineniN. McConkeyD.J. KamatA.M. SvatekR.S. PortenS.P. MeeksJ.J. LernerS.P. DinneyC.P. BlackP.C. McKiernanJ.M. AndersonC. DrakeC.G. BivalacquaT.J. Adaptive immune resistance to intravesical BCG in non–muscle invasive bladder cancer: Implications for prospective BCG-unresponsive trials.Clin. Cancer Res.202026488289110.1158/1078‑0432.CCR‑19‑192031712383
    [Google Scholar]
  44. HannounehZ.A. HijaziA. AlsaleemA.A. HamiS. KheyrbekN. TanousF. KhaddourK. AbbasA. AlshehabiZ. Novel immunotherapeutic options for BCG-unresponsive high-risk non-muscle-invasive bladder cancer.Cancer Med.20231224219442196810.1002/cam4.676838037752
    [Google Scholar]
  45. ErdoğarN. IskitA.B. EroğluH. SargonM.F. MunganN. BilensoyE. Antitumor efficacy of bacillus calmette-guerin loaded cationic nanoparticles for intravesical immunotherapy of bladder tumor induced rat model.J. Nanosci. Nanotechnol.20151512101561016410.1166/jnn.2015.1169026682462
    [Google Scholar]
  46. ZhangD. SunP. LiP. XueA. ZhangX. ZhangH. JinX. A magnetic chitosan hydrogel for sustained and prolonged delivery of Bacillus Calmette–Guérin in the treatment of bladder cancer.Biomaterials20133438102581026610.1016/j.biomaterials.2013.09.02724070571
    [Google Scholar]
  47. YoshinoT. MiyazakiJ. KojimaT. KandoriS. ShigaM. KawaharaT. KimuraT. NakaT. KiyoharaH. WatanabeM. YamasakiS. AkazaH. YanoI. NishiyamaH. Cationized liposomal keto-mycolic acids isolated from Mycobacterium bovis bacillus Calmette-Guérin induce antitumor immunity in a syngeneic murine bladder cancer model.PLoS One2019141020919610.1371/journal.pone.020919630608942
    [Google Scholar]
  48. WhangY.M. YoonD.H. HwangG.Y. YoonH. ParkS.I. ChoiY.W. ChangI.H. Liposome-encapsulated bacillus calmette–guérin cell wall skeleton enhances antitumor efficiency for bladder cancer in vitro and in vivo via induction of AMP-activated protein kinase.Cancers20201212367910.3390/cancers1212367933302414
    [Google Scholar]
  49. NakamuraT. FukiageM. HiguchiM. NakayaA. YanoI. MiyazakiJ. NishiyamaH. AkazaH. ItoT. HosokawaH. NakayamaT. HarashimaH. Nanoparticulation of BCG-CWS for application to bladder cancer therapy.J. Control. Release2014176445310.1016/j.jconrel.2013.12.02724389133
    [Google Scholar]
  50. YoonH.Y. YangH.M. KimC.H. GooY.T. HwangG.Y. ChangI.H. WhangY.M. ChoiY.W. Enhanced intracellular delivery of BCG cell wall skeleton into bladder cancer cells using liposomes functionalized with folic acid and Pep-1 peptide.Pharmaceutics2019111265210.3390/pharmaceutics1112065231817179
    [Google Scholar]
  51. MasudaH. NakamuraT. NomaY. HarashimaH. Application of BCG-CWS as a systemic adjuvant by using nanoparticulation technology.Mol. Pharm.201815125762577110.1021/acs.molpharmaceut.8b0091930380885
    [Google Scholar]
  52. MiyazakiJ. NishiyamaH. YanoI. NakayaA. KohamaH. KawaiK. JorakuA. NakamuraT. HarashimaH. AkazaH. The therapeutic effects of R8-liposome-BCG-CWS on BBN-induced rat urinary bladder carcinoma.Anticancer Res.20113162065207121737624
    [Google Scholar]
  53. RentschC.A. BosshardP. MayorG. RiekenM. PüschelH. WirthG. CathomasR. ParzmairG.P. GrodeL. EiseleB. SharmaH. GuptaM. GairolaS. ShaligramU. GoldenbergerD. SpertiniF. AudranR. EnoiuM. BerardiS. HayozS. WickiA. Results of the phase I open label clinical trial SAKK 06/14 assessing safety of intravesical instillation of VPM1002BC, a recombinant mycobacterium Bacillus Calmette Guérin (BCG), in patients with non-muscle invasive bladder cancer and previous failure of conventional BCG therapy.OncoImmunology202091174898110.1080/2162402X.2020.174898132363120
    [Google Scholar]
  54. RentschC.A. ThalmannG.N. LuccaI. KwiatkowskiM. WirthG.J. StrebelR.T. EngelerD. PedrazziniA. HüttenbrinkC. Schultze-SeemannW. TorpaiR. BubendorfL. WickiA. RothB. BosshardP. PüschelH. BollD.T. HefermehlL. RoghmannF. GierthM. RibiK. SchäferS. HayozS. A phase 1/2 single-arm clinical trial of recombinant Bacillus Calmette-Guérin (BCG) VPM1002BC immunotherapy in non–muscle-invasive bladder cancer recurrence after conventional BCG Therapy: SAKK 06/14.Eur. Urol. Oncol.20225219520210.1016/j.euo.2021.12.00635012889
    [Google Scholar]
  55. UmP.K. PraharajM. LombardoK.A. YoshidaT. MatosoA. BarasA.S. Improved bladder cancer antitumor efficacy with a recombinant BCG that releases a STING agonist.bioRxiv20232023.12.15.571740
    [Google Scholar]
  56. FDA D.I.S.C.O. Burst Edition: FDA approval of Adstiladrin (nadofaragene firadenovec-vncg) for patients with high-risk Bacillus Calmette-Guérin unresponsive non-muscle invasive bladder cancer with carcinoma in situ with or without papillary tumors.2024Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-disco-burst-edition-fda-approval-adstiladrin-nadofaragene-firadenovec-vncg-patients-high-risk
  57. BoorjianS.A. AlemozaffarM. KonetyB.R. ShoreN.D. GomellaL.G. KamatA.M. BivalacquaT.J. MontgomeryJ.S. LernerS.P. BusbyJ.E. PochM. CrispenP.L. SteinbergG.D. SchuckmanA.K. DownsT.M. SvatekR.S. MashniJ.Jr LaneB.R. GuzzoT.J. BratslavskyG. KarshL.I. WoodsM.E. BrownG. CanterD. LucheyA. LotanY. KrupskiT. InmanB.A. WilliamsM.B. CooksonM.S. KeeganK.A. AndrioleG.L.Jr SankinA.I. BoydA. O’DonnellM.A. SawutzD. PhilipsonR. CollR. NarayanV.M. TreasureF.P. Yla-HerttualaS. ParkerN.R. DinneyC.P.N. Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: A single-arm, open-label, repeat-dose clinical trial.Lancet Oncol.202122110711710.1016/S1470‑2045(20)30540‑433253641
    [Google Scholar]
  58. PapageorgiouA. DinneyC.P.N. McConkeyD.J. Interferon-alpha induces TRAIL expression and cell death via an IRF-1-dependent mechanism in human bladder cancer cells.Cancer Biol. Ther.20076687287910.4161/cbt.6.6.408817617740
    [Google Scholar]
  59. PapageorgiouA. LashingerL. MillikanR. GrossmanH.B. BenedictW. DinneyC.P.N. McConkeyD.J. Role of tumor necrosis factor-related apoptosis-inducing ligand in interferon-induced apoptosis in human bladder cancer cells.Cancer Res.200464248973897910.1158/0008‑5472.CAN‑04‑190915604261
    [Google Scholar]
  60. DinneyC.P. BielenbergD.R. PerrotteP. ReichR. EveB.Y. BucanaC.D. FidlerI.J. Inhibition of basic fibroblast growth factor expression, angiogenesis, and growth of human bladder carcinoma in mice by systemic interferon-alpha administration.Cancer Res.19985848088149485039
    [Google Scholar]
  61. SlatonJ.W. PerrotteP. InoueK. DinneyC.P. FidlerI.J. Interferon-alpha-mediated down-regulation of angiogenesis-related genes and therapy of bladder cancer are dependent on optimization of biological dose and schedule.Clin. Cancer Res.19995102726273410537335
    [Google Scholar]
  62. GreenJ.L. OsterhoutR.E. KlovaA.L. MerkwirthC. McDonnellS.R.P. ZavarehR.B. FuchsB.C. KamalA. JakobsenJ.S. Molecular characterization of type I IFN-induced cytotoxicity in bladder cancer cells reveals biomarkers of resistance.Mol. Ther. Oncolytics20212354755910.1016/j.omto.2021.11.00634938855
    [Google Scholar]
  63. MedranoR.F.V. HungerA. MendonçaS.A. BarbutoJ.A.M. StraussB.E. Immunomodulatory and antitumor effects of type I interferons and their application in cancer therapy.Oncotarget2017841712497128410.18632/oncotarget.1953129050360
    [Google Scholar]
  64. BenedictW.F. TaoZ. KimC.S. ZhangX. ZhouJ.H. AdamL. McConkeyD.J. PapageorgiouA. MunsellM. PhilopenaJ. EnglerH. DemersW. ManevalD.C. DinneyC.P.N. ConnorR.J. Intravesical Ad-IFNalpha causes marked regression of human bladder cancer growing orthotopically in nude mice and overcomes resistance to IFN-alpha protein.Mol. Ther.200410352553210.1016/j.ymthe.2004.05.02715336652
    [Google Scholar]
  65. ConnorR.J. AndersonJ.M. MachemerT. ManevalD.C. EnglerH. Sustained intravesical interferon protein exposure is achieved using an adenoviral-mediated gene delivery system: A study in rats evaluating dosing regimens.Urology200566122422910.1016/j.urology.2005.02.01515992886
    [Google Scholar]
  66. YamashitaM. RosserC.J. ZhouJ.H. ZhangX.Q. ConnorR.J. EnglerH. ManevalD.C. KarashimaT. CzerniakB.A. DinneyC.P.N. BenedictW.F. Syn3 provides high levels of intravesical adenoviral-mediated gene transfer for gene therapy of genetically altered urothelium and superficial bladder cancer.Cancer Gene Ther.20029868769110.1038/sj.cgt.770048812136430
    [Google Scholar]
  67. DinneyC.P.N. FisherM.B. NavaiN. O’DonnellM.A. CutlerD. AbrahamA. YoungS. HutchinsB. CaceresM. KishnaniN. SodeG. CullenC. ZhangG. GrossmanH.B. KamatA.M. GonzalesM. KincaidM. AinslieN. ManevalD.C. WszolekM.F. BenedictW.F. Phase I trial of intravesical recombinant adenovirus mediated interferon-α2b formulated in Syn3 for Bacillus Calmette-Guérin failures in nonmuscle invasive bladder cancer.J. Urol.2013190385085610.1016/j.juro.2013.03.03023507396
    [Google Scholar]
  68. NavaiN. BenedictW.F. ZhangG. AbrahamA. AinslieN. ShahJ.B. GrossmanH.B. KamatA.M. DinneyC.P.N. Phase 1b trial to evaluate tissue response to a second dose of intravesical recombinant adenoviral interferon α2b formulated in syn3 for failures of bacillus Calmette–Guerin (BCG) therapy in nonmuscle invasive bladder cancer.Ann. Surg. Oncol.201623124110411410.1245/s10434‑016‑5300‑627387678
    [Google Scholar]
  69. GiguèreC.M. BaumanN.M. SatoY. BurkeD.K. GreinwaldJ.H. PranskyS. KelleyP. GeorgesonK. SmithR.J.H. Treatment of lymphangiomas with OK-432 (Picibanil) sclerotherapy: A prospective multi-institutional trial.Arch. Otolaryngol. Head Neck Surg.2002128101137114410.1001/archotol.128.10.113712365884
    [Google Scholar]
  70. RyomaY. MoriyaY. OkamotoM. KanayaI. SaitoM. SatoM. Biological effect of OK-432 (picibanil) and possible application to dendritic cell therapy.Anticancer Res.2004245C3295330115515424
    [Google Scholar]
  71. U.S. Food and Drug Administration.2024Available from: https://www.fda.gov/
  72. Gomes-GiacoiaE. MiyakeM. GoodisonS. SriharanA. ZhangG. YouL. EganJ.O. RhodeP.R. ParkerA.S. ChaiK.X. WongH.C. RosserC.J. Intravesical ALT-803 and BCG treatment reduces tumor burden in a carcinogen induced bladder cancer rat model; a role for cytokine production and NK cell expansion.PLoS One2014969670510.1371/journal.pone.009670524896845
    [Google Scholar]
  73. RizviN.A. HellmannM.D. SnyderA. KvistborgP. MakarovV. HavelJ.J. LeeW. YuanJ. WongP. HoT.S. MillerM.L. RekhtmanN. MoreiraA.L. IbrahimF. BruggemanC. GasmiB. ZappasodiR. MaedaY. SanderC. GaronE.B. MerghoubT. WolchokJ.D. SchumacherT.N. ChanT.A. Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer.Science2015348623012412810.1126/science.aaa134825765070
    [Google Scholar]
  74. FinnO.J. Cancer Immunology.N. Engl. J. Med.2008358252704271510.1056/NEJMra07273918565863
    [Google Scholar]
  75. ChamieK ChangSS KramolowskyE GonzalgoML AgarwalPK BassettJC IL-15 superagonist NAI in BCG-unresponsive non-muscle-invasive bladder cancer.NEJM Evid202321EVIDoa220016710.1056/EVIDoa220016738320011
    [Google Scholar]
  76. FDA approves nogapendekin alfa inbakicept-pmln for BCG-unresponsive non-muscle invasive bladder cancer.2024Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nogapendekin-alfa-inbakicept-pmln-bcg-unresponsive-non-muscle-invasive-bladder-cancer
  77. JenkinsR.W. BarbieD.A. FlahertyK.T. Mechanisms of resistance to immune checkpoint inhibitors.Br. J. Cancer2018118191610.1038/bjc.2017.43429319049
    [Google Scholar]
  78. Pembrolizumab (Keytruda): Advanced or Metastatic Urothelial Carcinoma.2019Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/pembrolizumab-keytruda-advanced-or-metastatic-urothelial-carcinoma
  79. FDA approves pembrolizumab for BCG-unresponsive, high-risk non-muscle invasive bladder cancer.2024Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-bcg-unresponsive-high-risk-non-muscle-invasive-bladder-cancer
  80. MeghaniK. FrydenlundN. YuY. ChoyB. MeeksJ.J. Spatial comparison of molecular features associated with resistance to pembrolizumab in BCG unresponsive bladder cancer.J. Immunother. Cancer202412400857110.1136/jitc‑2023‑00857138631711
    [Google Scholar]
  81. MeghaniK. CooleyL.F. ChoyB. KocherginskyM. SwaminathanS. MunirS.S. First in human intravesical delivery of pembrolizumab identifies immune activation in BCG-unresponsive bladder cancer.Eur. Urol.202282660261010.1016/j.eururo.2022.08.00436008193
    [Google Scholar]
  82. WoodcockV.K. ChenJ.L. PurshouseK. ButcherC. CollinsL. HaddonC. VerrallG. ElhusseinL. RobertsC. TarltonA. ReiM. NapolitaniG. SalioM. MiddletonM.R. CerundoloV. CrewJ. ProtheroeA.S. PemBla: A Phase 1 study of intravesical pembrolizumab in recurrent non-muscle-invasive bladder cancer.BJUI Compass20234332233010.1002/bco2.22037025470
    [Google Scholar]
  83. BlackP.C. TangenC. SinghP. McConkeyD.J. LuciaS. LowranceW.T. Phase II trial of atezolizumab in BCG-unresponsive non-muscle invasive bladder cancer: SWOG S1605 (NCT #02844816).J Clin Oncol2020385022502210.1200/JCO.2020.38.15_suppl.5022
    [Google Scholar]
  84. RoupretM. NeuzilletY. BertautA. PignotG. HouedeN. ChampiatS. Nénan-Le FicherS. ChaussonM. LoriotY. ALBAN: An open label, randomized, phase III trial, evaluating efficacy of atezolizumab in addition to one year BCG (bacillus Calmette-Guerin) bladder instillation in BCG-naive patients with high-risk nonmuscle invasive bladder cancer (AFU-GETUG 37).J. Clin. Oncol.20193715_supplSuppl.TPS4589TPS458910.1200/JCO.2019.37.15_suppl.TPS4589
    [Google Scholar]
  85. LidagosterS. Ben-DavidR. De LeonB. SfakianosJ.P. BCG and alternative therapies to BCG therapy for non-muscle-invasive bladder cancer.Curr. Oncol.20243121063107810.3390/curroncol3102007938392073
    [Google Scholar]
  86. GrandiP. DarilekA. MoscuA. PradhanA. LiR. Intravesical infusion of oncolytic virus CG0070 in the treatment of bladder cancer.Methods Mol. Biol.2023268430331710.1007/978‑1‑0716‑3291‑8_1937410243
    [Google Scholar]
  87. MorizawaY. MiyakeM. ShimadaK. HoriS. TatsumiY. NakaiY. TanakaN. FujiiT. FujimotoK. Colony-stimulating factors detected in tumor cells and voided urine are potential prognostic markers for patients with muscle-invasive bladder cancer undergoing radical cystectomy.Res. Rep. Urol.20181010311110.2147/RRU.S16649730288389
    [Google Scholar]
  88. RameshN. GeY. EnnistD.L. ZhuM. MinaM. GaneshS. ReddyP.S. YuD.C. CG0070, a conditionally replicating granulocyte macrophage colony-stimulating factor--armed oncolytic adenovirus for the treatment of bladder cancer.Clin. Cancer Res.200612130531310.1158/1078‑0432.CCR‑05‑105916397056
    [Google Scholar]
  89. BurkeJ.M. LammD.L. MengM.V. NemunaitisJ.J. StephensonJ.J. ArseneauJ.C. AimiJ. LernerS. YeungA.W. KazarianT. MaslyarD.J. McKiernanJ.M. A first in human phase 1 study of CG0070, a GM-CSF expressing oncolytic adenovirus, for the treatment of nonmuscle invasive bladder cancer.J. Urol.201218862391239710.1016/j.juro.2012.07.09723088985
    [Google Scholar]
  90. PackiamV.T. LammD.L. BarocasD.A. TrainerA. FandB. DavisR.L.III ClarkW. KroegerM. DumbadzeI. ChamieK. KaderA.K. CurranD. GutheilJ. KuanA. YeungA.W. SteinbergG.D. An open label, single-arm, phase II multicenter study of the safety and efficacy of CG0070 oncolytic vector regimen in patients with BCG-unresponsive non–muscle-invasive bladder cancer: Interim results.Urol. Oncol.2018361044044710.1016/j.urolonc.2017.07.00528755959
    [Google Scholar]
  91. LiR. SteinbergG.D. UchioE.M. CORE1: Phase 2, single-arm study of CG0070 combined with pembrolizumab in patients with nonmuscle-invasive bladder cancer (NMIBC) unresponsive to bacillus Calmette-Guerin (BCG).J Clin Oncol2022404597459710.1200/JCO.2022.40.16_suppl.4597
    [Google Scholar]
  92. ZhangJ.H. StarrS.L. ChamieK. Novel delivery mechanisms for existing systemic agents and emerging therapies in bladder cancer.Bladder Cancer20239210912310.3233/BLC‑22011438993290
    [Google Scholar]
  93. UchioE.M. LammD.L. ShoreN.D. KamatA.M. TysonM. TranB. AndersonP. GrandiP. BurkeJ.M. A phase 3, single-arm study of CG0070 in subjects with nonmuscle invasive bladder cancer (NMIBC) unresponsive to Bacillus Calmette-Guerin (BCG).J. Clin. Oncol.2022406_supplTPS598TPS59810.1200/JCO.2022.40.6_suppl.TPS598
    [Google Scholar]
  94. GoldbergI.P. LichtbrounB. SingerE.A. GhodoussipourS. Pharmacologic therapies for non-muscle invasive bladder cancer: Current and future treatments.Arch. Pharmacol. Ther.202241132236051251
    [Google Scholar]
  95. ChangE. WeinstockC. ZhangL. CharlabR. DorffS.E. GongY. HsuV. LiF. RicksT.K. SongP. TangS. WaldronP.E. YuJ. ZahalkaE. GoldbergK.B. PazdurR. TheoretM.R. IbrahimA. BeaverJ.A. FDA approval summary: Enfortumab vedotin for locally advanced or metastatic urothelial carcinoma.Clin. Cancer Res.202127492292710.1158/1078‑0432.CCR‑20‑227532962979
    [Google Scholar]
  96. KamatA.M. LotanY. RoupretM. SteinbergG.D. InmanB.A. PowlesT. RedortaJ.P. PortenS.P. KulkarniG.S. UchioE.M. GorlaS.R. HaasG.P. YuY. ChiaY.L. BirrenkottM. KatesM.R. A first-in-human trial of intravesical enfortumab vedotin (EV), an antibody-drug conjugate (ADC), in patients with non-muscle invasive bladder cancer (NMIBC): Interim results of a phase 1 study (EV-104).J. Clin. Oncol.20234116_suppl4596459610.1200/JCO.2023.41.16_suppl.4596
    [Google Scholar]
  97. KowalskiM. GuindonJ. BrazasL. MooreC. EntwistleJ. CizeauJ. JewettM.A.S. MacDonaldG.C. A phase II study of oportuzumab monatox: An immunotoxin therapy for patients with noninvasive urothelial carcinoma in situ previously treated with bacillus Calmette-Guérin.J. Urol.201218851712171810.1016/j.juro.2012.07.02022998907
    [Google Scholar]
  98. O’DonnellM. ShoreN. KeaneT. JewettM. DicksteinR. WolkF. DillonR.L. CizeauJ. KassoufW. Mp16-03 phase 3 study of vicineum in bcg-unresponsive non-muscle invasive bladder cancer: 24-month results.J. Urol.2021206Suppl. 329610.1097/JU.0000000000002001.03
    [Google Scholar]
  99. Rivera-MarquezG. WalterB. DolanR. BelfieldS. MerinoM. GurramS. MP16-20: Final results of a phase I, single-arm clinical trial of the combination of durvalumab and vicineum in BCG unresponsive, high-risk non-muscle-invasive bladder cancer patients (NCT03258593).J Urol20242115Se24810.1097/01.JU.0001008640.01272.9d.20
    [Google Scholar]
  100. BroderickJ.M. FDA does not approve Vicineum for bladder cancer.2021Available from: https://www.urologytimes.com/view/fda-does-not-approve-vicineum-for-bladder-cancer
  101. CamargoJ.A. PassosG.R. FerrariK.L. BillisA. SaadM.J.A. ReisL.O. Intravesical immunomodulatory imiquimod enhances bacillus calmette-guérin downregulation of nonmuscle-invasive bladder cancer.Clin. Genitourin. Cancer2018163e587e59310.1016/j.clgc.2017.10.01929174504
    [Google Scholar]
  102. ArendsT.J.H. LammersR.J.M. FalkeJ. van der HeijdenA.G. RustighiniI. PozziR. RavicM. EisenhardtA. VergunstH. WitjesJ.A. Pharmacokinetic, pharmacodynamic, and activity evaluation of TMX-101 in a multicenter phase 1 study in patients with papillary non-muscle-invasive bladder cancer.Clin. Genitourin. Cancer2015133204209.e210.1016/j.clgc.2014.12.01025660383
    [Google Scholar]
  103. DoninN.M. ChamieK. LenisA.T. PantuckA.J. ReddyM. KivlinD. HolldackJ. PozziR. HakimG. KarshL.I. LammD.L. BelkoffL.H. BelldegrunA.S. HoldenS. ShoreN. A phase 2 study of TMX-101, intravesical imiquimod, for the treatment of carcinoma in situ bladder cancer.Urol. Oncol.201735239.e139.e710.1016/j.urolonc.2016.09.00628341495
    [Google Scholar]
  104. FalkeJ. Hulsbergen-van de KaaC.A. MajR. OosterwijkE. WitjesJ.A. A placebo-controlled efficacy study of the intravesical immunomodulators TMX-101 and TMX-202 in an orthotopic bladder cancer rat model.World J. Urol.201836111719172510.1007/s00345‑018‑2334‑329767328
    [Google Scholar]
  105. PortalD.E. WeissR.E. WojtowiczM. MansourA. MonkenC. MehnertJ.M. AisnerJ.A. KaneM. NishiokaJ. AisnerS. PetersS. SteinM.N. KimI.Y. MayerT.M. ShihW. GulleyJ. StreicherH. SingerE.A. LattimeE.C. Phase I neoadjuvant study of intravesical recombinant fowlpox-GM-CSF (rF-GM-CSF) or fowlpox-TRICOM (rF-TRICOM) in patients with bladder carcinoma.Cancer Gene Ther.202027643844710.1038/s41417‑019‑0112‑z31222182
    [Google Scholar]
  106. BandariJ. ZummoJ. BelaniK. BrownE. MetcalfM. NanayakkaraN. Phase 1a/b safety study of intravesical instillation of TARA-002 in adults with high-grade non-muscle invasive bladder cancer (ADVANCED-1).J. Clin. Oncol.20224016_supplSuppl.TPS4620TPS462010.1200/JCO.2022.40.16_suppl.TPS4620
    [Google Scholar]
  107. BandariJ. JayramG. TabayoyongW. MessingE. ShahP.H. ShoreN.D. BandariJ. ZummoJ. SunW. BelaniK. BrownE. MetcalfM.K. NanayakkaraN. Advanced-1: Phase 1a dose-finding, open-label study to evaluate safety and toxicity of intravesical instillation of TARA-002 in adults with high-grade non-muscle invasive bladder cancer.Urol. Oncol.202442S6110.1016/j.urolonc.2024.01.179
    [Google Scholar]
  108. KalotaS. JoshiS. BuiM. DicksteinR. LiuJ.J. LotanY. P2-08: LEGEND: A phase 1/2 study of EG-70 (detalimogene voraplasmid), a novel, non-viral intravesical gene therapy for patients with BCG-unresponsive non-muscle invasive bladder cancer with carcinoma in situ (CIS).J Urol20242115S2e510.1097/01.JU.0001015816.87470.c9
    [Google Scholar]
  109. BornM. PahnerI. Ahnert-HilgerG. JönsT. The maintenance of the permeability barrier of bladder facet cells requires a continuous fusion of discoid vesicles with the apical plasma membrane.Eur. J. Cell Biol.200382734335010.1078/0171‑9335‑0032612924629
    [Google Scholar]
  110. ChehroudiA.C. BlackP.C. Emerging intravesical therapies for the management of bacillus Calmette–Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer: Charting a path forward.Can. Urol. Assoc. J.202014620421310.5489/cuaj.610131977307
    [Google Scholar]
  111. PortenS. LeapmanM. GreeneK. Intravesical chemotherapy in non-muscle-invasive bladder cancer.Indian J. Urol.201531429730310.4103/0970‑1591.16644626604440
    [Google Scholar]
  112. DeCastroG.J. SuiW. PakJ.S. LeeS.M. HolderD. KatesM.M. VirkR.K. DrakeC.G. AndersonC.B. JamesB. Abate-ShenC.T. McKiernanJ.M. A phase I Trial of intravesical cabazitaxel, gemcitabine and cisplatin for the treatment of nonmuscle invasive bacillus calmette-guérin unresponsive or recurrent/relapsing urothelial carcinoma of the bladder.J. Urol.2020204224725310.1097/JU.000000000000091932118506
    [Google Scholar]
  113. MoussaM. Abou ChakraM. ShoreN.D. PapatsorisA. FarahatY. O’DonnellM.A. Patterns of treatment of high-risk BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) patients among Arab urologists.Arch. Ital. Urol. Androl.20249611224410.4081/aiua.2024.1224438502039
    [Google Scholar]
  114. PazM.M. ZhangX. LuJ. HolmgrenA. A new mechanism of action for the anticancer drug mitomycin C: Mechanism-based inhibition of thioredoxin reductase.Chem. Res. Toxicol.20122571502151110.1021/tx300206522694104
    [Google Scholar]
  115. HayneD. StocklerM. McCombieS.P. ChalasaniV. LongA. MartinA. SenguptaS. DavisI.D. BCG+MMC trial: Adding mitomycin C to BCG as adjuvant intravesical therapy for high-risk, non-muscle-invasive bladder cancer: A randomised phase III trial (ANZUP 1301).BMC Cancer201515143210.1186/s12885‑015‑1431‑626014129
    [Google Scholar]
  116. GrimbergD.C. DudinecJ. ShahA. InmanB.A. Clinical trial of high dose hyperthermic intravesical mitomycin C for intermediate and high-risk non–muscle invasive bladder cancer during BCG shortage.Urol. Oncol.2021398498.e13498.e2010.1016/j.urolonc.2020.12.02533485761
    [Google Scholar]
  117. HendricksenK. Device-assisted intravesical therapy for non-muscle invasive bladder cancer.Transl. Androl. Urol.2019819410010.21037/tau.2018.09.0930976573
    [Google Scholar]
  118. van den TempelN. NaipalK.A.T. RaamsA. van GentD.C. FranckenaM. BoormansJ.L. KanaarR. ex-vivo assays to predict enhanced chemosensitization by hyperthermia in urothelial cancer of the bladder.PLoS One20181312020910110.1371/journal.pone.020910130550547
    [Google Scholar]
  119. ColomboR. LevA. Da PozzoL.F. FreschiM. GallusG. RigattiP. A new approach using local combined microwave hyperthermia and chemotherapy in superficial transitional bladder carcinoma treatment.J. Urol.19951533S95996310.1016/S0022‑5347(01)67613‑47853583
    [Google Scholar]
  120. LeeH.W. LeeH.H. ParkE.Y. ParkW.S. KimS.H. JoungJ.Y. ChungJ. SeoH.K. Clinical efficacy of neoadjuvant intravesical mitomycin-c therapy immediately before transurethral resection of bladder tumor in patients with nonmuscle-invasive bladder cancer: Preliminary results of a prospective, randomized phase II study.J. Urol.2023209113113910.1097/JU.000000000000300236250938
    [Google Scholar]
  121. KleinmannN. MatinS.F. PierorazioP.M. GoreJ.L. ShabsighA. HuB. ChamieK. GodoyG. HuboskyS. RiveraM. O’DonnellM. QuekM. RamanJ.D. KnoedlerJ.J. ScherrD. SternJ. WeightC. WeizerA. WoodsM. KaimakliotisH. SmithA.B. LinehanJ. ColemanJ. HumphreysM.R. PakR. LifshitzD. VerniM. AdibiM. AminM.B. SeltzerE. KleinI. KonortyM. Strauss-AyaliD. HakimG. SchoenbergM. LernerS.P. Primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel (OLYMPUS): An open-label, single-arm, phase 3 trial.Lancet Oncol.202021677678510.1016/S1470‑2045(20)30147‑932631491
    [Google Scholar]
  122. PrasadS.M. HuangW.C. ShoreN.D. HuB. BjurlinM. BrownG. GenovP. ShishkovD. KhuskivadzeA. GanevT. MarchevD. OrlovI. KopyltsovE. ZubarevV. NosovA. KomlevD. BurgerB. RajuS. MeadsA. SchoenbergM. Treatment of low-grade intermediate-risk nonmuscle-invasive bladder cancer With UGN-102 ± transurethral resection of bladder tumor compared to transurethral resection of bladder tumor monotherapy: A randomized, controlled, phase 3 trial (ATLAS).J. Urol.2023210461962910.1097/JU.000000000000364537548555
    [Google Scholar]
  123. GiannantoniA. Di StasiS.M. ChancellorM.B. CostantiniE. PorenaM. New frontiers in intravesical therapies and drug delivery.Eur. Urol.20065061183119310.1016/j.eururo.2006.08.02516963179
    [Google Scholar]
  124. DecaesteckerK. LumenN. Van CampC. OosterlinckW. Single ablative intravesical electromotive mitomycin C administration for small non-muscle-invasive bladder cancer: A prospective study.Acta Clin. Belg.20187351410.1080/17843286.2018.144070629451102
    [Google Scholar]
  125. EkinR.G. AkarkenI. CakmakO. TarhanH. CelikO. IlbeyY.O. DivrikR.T. ZorluF. Results of intravesical chemo-hyperthermia in high-risk non-muscle invasive bladder cancer.Asian Pac. J. Cancer Prev.20151683241324510.7314/APJCP.2015.16.8.324125921126
    [Google Scholar]
  126. LiuK. ZhuJ. SongY.X. WangX. ZhouK.C. LuY. LiuX.Q. Thermal intravesical chemotherapy reduce recurrence rate for non-muscle invasive bladder cancer patients: A meta-analysis.Front. Oncol.2020102910.3389/fonc.2020.0002932117709
    [Google Scholar]
  127. PijpersO.M. HendricksenK. MostafidH. de JongF.C. RosierM. MayorN. de JongJ.J. BoormansJ.L. Long-term efficacy of hyperthermic intravesical chemotherapy for BCG-unresponsive non-muscle invasive bladder cancer.Urol. Oncol.202240262.e1362.e2010.1016/j.urolonc.2021.07.01934470725
    [Google Scholar]
  128. MagalhãesJ.C. SousaM. BastoR. FragaT. GomesI. FernandesC. MarianoM. PauloJ. MadeiraP. SousaG. Adjuvant hyperthermic intravesical chemotherapy in intermediate- and high-risk non-muscle invasive bladder cancer.Cureus20231594567210.7759/cureus.4567237745737
    [Google Scholar]
  129. ScosyrevE. Neoadjuvant gemcitabine and cisplatin chemotherapy for locally advanced urothelial cancer of the bladder.Cancer20121181728110.1002/cncr.2623821720989
    [Google Scholar]
  130. von der MaaseH. HansenS.W. RobertsJ.T. DogliottiL. OliverT. MooreM.J. BodrogiI. AlbersP. KnuthA. LippertC.M. KerbratP. Sanchez RoviraP. WersallP. CleallS.P. RoychowdhuryD.F. TomlinI. Visseren-GrulC.M. ConteP.F. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: Results of a large, randomized, multinational, multicenter, phase III study.J. Clin. Oncol.200018173068307710.1200/JCO.2000.18.17.306811001674
    [Google Scholar]
  131. LuJ.L. XiaQ.D. LiuC.Q. SunJ.X. YangY.Y. HuH.L. WangS.G. Efficacy and toxicity in scheduled intravesical gemcitabine versus Bacille Calmette-Guérin for Ta and T1 bladder cancer: A systematic review and meta-analysis.Transl. Cancer Res.20211062849285810.21037/tcr‑21‑29135116595
    [Google Scholar]
  132. MessingE.M. TangenC.M. LernerS.P. SahasrabudheD.M. KoppieT.M. WoodD.P.Jr MackP.C. SvatekR.S. EvansC.P. HafezK.S. CulkinD.J. BrandT.C. KarshL.I. HolzbeierleinJ.M. WilsonS.S. WuG. PletsM. VogelzangN.J. ThompsonI.M.Jr Effect of intravesical instillation of gemcitabine vs saline immediately following resection of suspected low-grade non–muscle-invasive bladder cancer on tumor recurrence.JAMA2018319181880188810.1001/jama.2018.465729801011
    [Google Scholar]
  133. ChenT.Y. TsaiM.J. ChangL.C. WuP.C. Co-Delivery of cisplatin and gemcitabine via viscous nanoemulsion for potential synergistic intravesical chemotherapy.Pharmaceutics2020121094910.3390/pharmaceutics1210094933036448
    [Google Scholar]
  134. Abou ChakraM PackiamVT McElreeIM MottSL O’DonnellMA The efficacy of sequential intravesical gemcitabine and docetaxel versus BCG for the treatment of European Association of Urology very-high risk non-muscle invasive bladder cancer.Urol Oncol2025436390.e13390.e2210.1016/j.urolonc.2024.10.01239592360
    [Google Scholar]
  135. HurleR. CasaleP. MorenghiE. SaitaA. BuffiN. LughezzaniG. ColomboP. ContieriR. FregoN. GuazzoniG. LazzeriM. Intravesical gemcitabine as bladder-preserving treatment for BCG unresponsive non-muscle-invasive bladder cancer. Results from a single-arm, open-label study.BJUI Compass20201412613210.1002/bco2.2835474942
    [Google Scholar]
  136. MirzaeeE. NovinK. FadaviP. SoltaniS. Kafash NayeriR. AmanollahiA. ArefpourA.M. Intravesical gemcitabine for non-muscle invasive bladder cancer after bacillus calmette-guerin treatment failure: A prospective study.Asian Pac. J. Cancer Prev.20242593173317710.31557/APJCP.2024.25.9.317339342596
    [Google Scholar]
  137. ZhengB. ZhangH. WangJ. QinX. XuW. WangH. LiuZ. LiuY. MouY. LaiW.F. ShenY. ZhangD. ZhangP. A mucoadhesive-to-penetrating nanomotors-in-hydrogel system for urothelium-oriented intravesical drug delivery.J. Nanobiotechnology202422156010.1186/s12951‑024‑02816‑739272197
    [Google Scholar]
  138. BakulaM. HudolinT. KnezevicN. ZimakZ. AndelicJ. JuricI. GamulinM. GnjidicM. KastelanZ. Intravesical gemcitabine and docetaxel therapy for BCG-Naïve patients: A promising approach to non-muscle invasive bladder cancer.Life202414778910.3390/life1407078939063544
    [Google Scholar]
  139. GrimbergD.C. ShahA. InmanB.A. Overview of Taris GemRIS, a novel drug delivery system for bladder cancer.Eur. Urol. Focus20206462062210.1016/j.euf.2019.09.00631561993
    [Google Scholar]
  140. DaneshmandS. BrummelhuisI.S.G. PoharK.S. SteinbergG.D. AronM. CutieC.J. KeeganK.A. MaffeoJ.C. ReynoldsD.L. RayboldB. ChauA. WitjesJ.A. The safety, tolerability, and efficacy of a neoadjuvant gemcitabine intravesical drug delivery system (TAR-200) in muscle-invasive bladder cancer patients: A phase I trial.Urol. Oncol.2022407344.e1344.e910.1016/j.urolonc.2022.02.00935431132
    [Google Scholar]
  141. TysonM.D. MorrisD. PalouJ. RodriguezO. MirM.C. DicksteinR.J. Guerrero-RamosF. ScarpatoK.R. HafronJ.M. MessingE.M. CutieC.J. MaffeoJ.C. RayboldB. ChauA. StrombergK.A. KeeganK.A. Safety, tolerability, and preliminary efficacy of TAR-200 in patients with muscle-invasive bladder cancer who refused or were unfit for curative-intent therapy: A phase 1 study.J. Urol.2023209589090010.1097/JU.000000000000319537026631
    [Google Scholar]
  142. P van ValenbergF.J. van der HeijdenA.G. CutieC.J. BhanvadiaS. KeeganK.A. HamprasS. SweitiH. MaffeoJ.C. JinS. ChauA. ReynoldsD.L. IarossiC. KelleyA. LiX. StrombergK.A. Michiel SedelaarJ.P. SteenbruggenJ.J.O. SomfordD.M. Alfred WitjesJ. The safety, tolerability, and preliminary efficacy of a gemcitabine-releasing intravesical system (TAR-200) in American urological association-defined intermediate-risk non-muscle-invasive bladder cancer patients: A phase 1b study.Eur. Urol. Open Sci.20246281510.1016/j.euros.2024.01.01338585206
    [Google Scholar]
  143. HeijdenM.S.V.D. CutieC. HamprasS. IndoriaC. StewartR. AcharyaM. SunRISe-1: Phase 2b study of TAR-200 plus cetrelimab, TAR-200 alone, or cetrelimab alone in participants with high-risk nonmuscle-invasive bladder cancer unresponsive to Bacillus Calmette-Guérin who are ineligible for or decline radical cystectomy.J Clin Oncol202240TPS593TPS59310.1200/JCO.2022.40.6_suppl.TPS593
    [Google Scholar]
  144. VilasecaA. JayramG. RaventosC. ShoreN.D. ZainfeldD. KangT.W. KuJ.H. MeeksJ. Rodríguez FabaÓ. RoghmannF. DaneshmandS. BeeharryN. CostC. KalotaA. LauringJ. PetersonM. QuirozM. StoneN. ZhuW. Guerrero-RamosF. LBA104 First safety and efficacy results of the TAR-210 erdafitinib (erda) intravesical delivery system in patients (pts) with non–muscle-invasive bladder cancer (NMIBC) with select FGFR alterations (alt).Ann. Oncol.202334S134310.1016/j.annonc.2023.10.110
    [Google Scholar]
  145. HarrisJ. SunRISe-2 trial explores TAR-200/Cetrelimab for treatment of MIBC.2021Available from: https://www.targetedonc.com/view/sunrise-2-trial-explores-tar-200-cetrelimab-for-treatment-of-mibc
  146. LeeJ. ChoiM.K. SongI.S. Recent advances in doxorubicin formulation to enhance pharmacokinetics and tumor targeting.Pharmaceuticals202316680210.3390/ph1606080237375753
    [Google Scholar]
  147. JaiswalM.K. PradhanL. VasavadaS. DeM. SarmaH.D. PrakashA. BahadurD. DravidV.P. Magneto-thermally responsive hydrogels for bladder cancer treatment: Therapeutic efficacy and in vivo biodistribution.Colloids Surf. B Biointerfaces201513662563310.1016/j.colsurfb.2015.09.05826477008
    [Google Scholar]
  148. GuhaSarkarS. MoreP. BanerjeeR. Urothelium-adherent, ion-triggered liposome-in-gel system as a platform for intravesical drug delivery.J. Control. Release201724514715610.1016/j.jconrel.2016.11.03127913307
    [Google Scholar]
  149. LiT.J. HuangC.C. RuanP.W. ChuangK.Y. HuangK.J. ShiehD.B. YehC.S. in vivo anti-cancer efficacy of magnetite nanocrystal - based system using locoregional hyperthermia combined with 5-fluorouracil chemotherapy.Biomaterials201334327873788310.1016/j.biomaterials.2013.07.01223876757
    [Google Scholar]
  150. SarfrazM. QamarS. RehmanM.U. TahirM.A. IjazM. AhsanA. AsimM.H. NazirI. Nano-formulation based intravesical drug delivery systems: An overview of versatile approaches to improve urinary bladder diseases.Pharmaceutics2022149190910.3390/pharmaceutics1409190936145657
    [Google Scholar]
  151. LuoL. JinX. ZhangP. ChengH. LiY. DuT. ZouB. GouM. Efficient intravesical therapy of bladder cancer with cationic doxorubicin nanoassemblies.Int. J. Nanomedicine2016114535454410.2147/IJN.S10399427660445
    [Google Scholar]
  152. QiuX. CaoK. LinT. ChenW. YuanA. WuJ. HuY. GuoH. Drug delivery system based on dendritic nanoparticles for enhancement of intravesical instillation.Int. J. Nanomedicine2017127365737410.2147/IJN.S14011129066888
    [Google Scholar]
  153. WangJ. YangP. HouD. YanY. YueK. ZhongW. XiaoT. WuX. WangZ. WuP. WangL. WangH. XuW. Bacteria-inspired transformable nanoparticle targets and covers residual tumor against bladder cancer recurrence.Nano Today20224510155110.1016/j.nantod.2022.101551
    [Google Scholar]
  154. AliM.S. MetwallyA.A. FahmyR.H. OsmanR. Chitosan-coated nanodiamonds: Mucoadhesive platform for intravesical delivery of doxorubicin.Carbohydr. Polym.202024511652810.1016/j.carbpol.2020.11652832718632
    [Google Scholar]
  155. SiddiquiM.R. GrantC. SanfordT. AgarwalP.K. Current clinical trials in non–muscle invasive bladder cancer.Urol. Oncol.201735851652710.1016/j.urolonc.2017.06.04328778250
    [Google Scholar]
  156. BlancJ. RuggieroJ. LuccaI. ArnoldN. KissB. RothB. Hyperthermic intravesical chemotherapy (HIVEC) using epirubicin in an optimized setting in patients with NMIBC recurrence after failed BCG therapy.Cancers2024167139810.3390/cancers1607139838611077
    [Google Scholar]
  157. JiaoB. LiuK. GongH. DingZ. XuX. RenJ. ZhangG. YuQ. GanZ. Bladder cancer selective chemotherapy with potent NQO1 substrate co-loaded prodrug nanoparticles.J. Control. Release202234763264810.1016/j.jconrel.2022.05.03135618186
    [Google Scholar]
  158. JiangS.C. LiaoY.G. LuoJ. HuD. WangY.D. HeK. Comparison of intravesical chemotherapy regimens after radical nephroureterectomy for upper tract urothelial carcinoma and analysis of risk factors for postoperative recurrence.Eur. Rev. Med. Pharmacol. Sci.20242862387239510.26355/eurrev_202403_3574538567601
    [Google Scholar]
  159. DaryantoB. PurnomoA. SeputraK. BudayaT. Comparison between intravesical chemotherapy Epirubicin and Mitomycin-C after TURB vs TURB alone with recurrence rate of non-muscle invasive bladder cancer: Meta-analysis.Med. Arh.202276319820110.5455/medarh.2022.76.198‑20136200115
    [Google Scholar]
  160. HuoF. ZhangY. LiY. BuH. ZhangY. LiW. GuoY. WangL. JiaR. HuangT. ZhangW. LiP. DingL. YanC. Mannose-targeting concanavalin A−Epirubicin conjugate for targeted intravesical chemotherapy of bladder cancer.Chem. Asian J.2022171620220034210.1002/asia.20220034235713953
    [Google Scholar]
  161. WangY. ZhangY. LiP.C. GuoJ. HuoF. YangJ. JiaR. WangJ. HuangQ. TheodorescuD. YuH. YanC. Development of novel aptamer-based targeted chemotherapy for bladder cancer.Cancer Res.20228261128113910.1158/0008‑5472.CAN‑21‑269135064018
    [Google Scholar]
  162. ElkashefA. BarakatN. KhaterS.M. AwadallaA. BelalF. El-AssmyA.M. SheirK.Z. ShokeirA.A. Effect of low-energy shock wave therapy on intravesical epirubicin delivery in a rat model of bladder cancer.BJU Int.20211271808910.1111/bju.1517332654305
    [Google Scholar]
  163. SuoN. WangM. JinY. DingJ. GaoX. SunX. ZhangH. CuiM. ZhengJ. LiN. JinX. JiangS. Magnetic multiwalled carbon nanotubes with controlled release of epirubicin: An intravesical instillation system for bladder cancer.Int. J. Nanomedicine2019141241125410.2147/IJN.S18968830863057
    [Google Scholar]
  164. HajianR. HossainiP. MehrayinZ. WoiP.M. ShamsN. DNA-binding studies of valrubicin as a chemotherapy drug using spectroscopy and electrochemical techniques.J. Pharm. Anal.20177317618010.1016/j.jpha.2017.01.00329404035
    [Google Scholar]
  165. IsraelM. ModestE.J. FreiE.III N-trifluoroacetyladriamycin-14-valerate, an analog with greater experimental antitumor activity and less toxicity than adriamycin.Cancer Res.1975355136513681054622
    [Google Scholar]
  166. Álvarez-MaestroM. Guerrero-RamosF. Rodríguez-FabaO. Domínguez-EscrigJ.L. Fernández-GómezJ.M. Current treatments for BCG failure in non-muscle invasive bladder cancer (NMIBC).Actas Urol. Esp.20214529310210.1016/j.acuroe.2020.08.01133012593
    [Google Scholar]
  167. McElreeI.M. PackiamV.T. SteinbergR.L. MottS.L. GellhausP.T. NeppleK.G. O’DonnellM.A. Sequential intravesical valrubicin and docetaxel for the salvage treatment of non–muscle-invasive bladder cancer.J. Urol.2022208596997710.1097/JU.000000000000284835830552
    [Google Scholar]
  168. GalskyM.D. The role of taxanes in the management of bladder cancer.Oncologist2005101079279810.1634/theoncologist.10‑10‑79216314289
    [Google Scholar]
  169. MaruS. AbeT. ShinoharaN. SazawaA. MaruyamaS. HarabayashiT. SuzukiS. NonomuraK. Influence of baseline renal function and dose reduction of nephrotoxic chemotherapeutic agents on the outcome of metastatic urothelial carcinoma: A retrospective study.Int. J. Urol.201219211011610.1111/j.1442‑2042.2011.02913.x22126100
    [Google Scholar]
  170. TosiA. ParisattoB. GaffoE. BortoluzziS. RosatoA. A paclitaxel-hyaluronan conjugate (ONCOFID-P-B™) in patients with BCG-unresponsive carcinoma in situ of the bladder: A dynamic assessment of the tumor microenvironment.J. Exp. Clin. Cancer Res.202443110910.1186/s13046‑024‑03028‑538600583
    [Google Scholar]
  171. McKiernanJ.M. HolderD.D. GhandourR.A. BarlowL.J. AhnJ.J. KatesM. BadalatoG.M. RoychoudhuryA. DecastroG.J. BensonM.C. Phase II trial of intravesical nanoparticle albumin bound paclitaxel for the treatment of nonmuscle invasive urothelial carcinoma of the bladder after bacillus Calmette-Guérin treatment failure.J. Urol.201419261633163810.1016/j.juro.2014.06.08424996128
    [Google Scholar]
  172. TamuraK. KikuchiE. KonnoT. IshiharaK. MatsumotoK. MiyajimaA. OyaM. Therapeutic effect of intravesical administration of paclitaxel solubilized with poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) in an orthotopic bladder cancer model.BMC Cancer201515131710.1186/s12885‑015‑1338‑225928041
    [Google Scholar]
  173. ForetzM. GuigasB. BertrandL. PollakM. ViolletB. Metformin: From mechanisms of action to therapies.Cell Metab.201420695396610.1016/j.cmet.2014.09.01825456737
    [Google Scholar]
  174. ZhangX. HuX. XieY. XieL. ChenX. PengM. LiD. DengJ. XiaoD. YangX. Metformin-loaded chitosan hydrogels suppress bladder tumor growth in an orthotopic mouse model via intravesical administration.Molecules20232818672010.3390/molecules2818672037764495
    [Google Scholar]
  175. ZhaoW WangL ZhangM LiuZ WuC PanX Photodynamic therapy for cancer: Mechanisms, photosensitizers, nanocarriers, and clinical studies.MedComm20245760310.1002/mco2.60338911063
    [Google Scholar]
  176. KulkarniG.S. LilgeL. NesbittM. Dumoulin-WhiteR.J. MandelA. JewettM.A.S. A phase 1b clinical study of intravesical photodynamic therapy in patients with bacillus calmette-guérin–unresponsive non–muscle-invasive bladder cancer.Eur. Urol. Open Sci.20224110511110.1016/j.euros.2022.04.01535813250
    [Google Scholar]
  177. Ishay-RonenD. DiepenbruckM. KalathurR.K.R. SugiyamaN. TiedeS. IvanekR. BantugG. MoriniM.F. WangJ. HessC. ChristoforiG. Gain fat—lose metastasis: Converting invasive breast cancer cells into adipocytes inhibits cancer metastasis.Cancer Cell20193511732.e610.1016/j.ccell.2018.12.00230645973
    [Google Scholar]
  178. PlumberS.A. TateT. Al-AhmadieH. ChenX. ChoiW. BasarM. LuC. VinyA. BatourinaE. LiJ. GretarssonK. AlijaB. MolotkovA. WiessnerG. LeeB.H.L. McKiernanJ. McConkeyD.J. DinneyC. CzerniakB. MendelsohnC.L. Rosiglitazone and trametinib exhibit potent anti-tumor activity in a mouse model of muscle invasive bladder cancer.Nat. Commun.2024151653810.1038/s41467‑024‑50678‑239095358
    [Google Scholar]
  179. HuW. Harnessing natural pollen as sustained-release, mucoadhesive, and biosafe drug microcapsules for intravesical instillation in bladder cancer treatment.Small2024e240635110.1002/smll.20240635139654339
    [Google Scholar]
  180. ChenQ. SunL. ChenZ.J. Regulation and function of the cGAS–STING pathway of cytosolic DNA sensing.Nat. Immunol.201617101142114910.1038/ni.355827648547
    [Google Scholar]
  181. DecoutA. KatzJ.D. VenkatramanS. AblasserA. The cGAS–STING pathway as a therapeutic target in inflammatory diseases.Nat. Rev. Immunol.202121954856910.1038/s41577‑021‑00524‑z33833439
    [Google Scholar]
  182. MeeskeA.J. JiaN. CasselA.K. KozlovaA. LiaoJ. WiedmannM. PatelD.J. MarraffiniL.A. A phage-encoded anti-CRISPR enables complete evasion of type VI-A CRISPR-Cas immunity.Science20203696499545910.1126/science.abb615132467331
    [Google Scholar]
  183. LiangM. WangY. LiuL. DengD. YanZ. FengL. KongC. LiC. LiY. LiG. Synergistic intravesical instillation for bladder cancer: CRISPR-Cas13a and fenbendazole combination therapy.J. Exp. Clin. Cancer Res.202443122310.1186/s13046‑024‑03146‑039128990
    [Google Scholar]
/content/journals/cdt/10.2174/0113894501384020250804093144
Loading
/content/journals/cdt/10.2174/0113894501384020250804093144
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test