2024
DNA Damage Response Alterations Predict for Neoadjuvant Chemotherapy Sensitivity in Muscle-Invasive Bladder Cancer: A Correlative Analysis of the SWOG S1314 Trial
Iyer G, Tangen C, Sarfaty M, Regazzi A, Lee I, Fong M, Choi W, Dinney C, Flaig T, Thompson I, Lerner S, McConkey D, Rosenberg J. DNA Damage Response Alterations Predict for Neoadjuvant Chemotherapy Sensitivity in Muscle-Invasive Bladder Cancer: A Correlative Analysis of the SWOG S1314 Trial. JCO Precision Oncology 2024, 8: e2400287. PMID: 39499893, DOI: 10.1200/po.24.00287.Peer-Reviewed Original ResearchConceptsNeoadjuvant cisplatin-based chemotherapyMuscle-invasive bladder cancerProgression-free survivalDDR alterationsDNA damage response alterationPathological responseBladder cancerDNA damage responseAssociated with pathological responseNeoadjuvant chemotherapy sensitivityPretreatment tumor specimensPathological response rateCisplatin-based chemotherapyDNA damage response genesEstimates of hazard ratiosOverall survivalRadical cystectomyTumor specimensPerformance statusClinical stageChemotherapy sensitivityCox regressionHazard ratioNext-generation sequencingPatientsEligibility and Endpoints for Clinical Trials in Trimodality Therapy for Bladder Cancer
Singh P, Ballas L, Sonpavde G, Chen R, Bangs R, Bauman B, Nagar H, Delacroix S, Lerner S, Efstathiou J. Eligibility and Endpoints for Clinical Trials in Trimodality Therapy for Bladder Cancer. Bladder Cancer 2024, 10: 199-213. PMID: 39493817, PMCID: PMC11530036, DOI: 10.3233/blc-240036.Peer-Reviewed Original ResearchBladder cancer treatmentTransurethral resection of bladder tumorEastern Cooperative Oncology GroupTrimodality therapyLong-term outcomesClinical trialsCancer treatmentRadical cystectomySystemic therapyEligibility criteriaSecondary endpointsTrial eligibility criteriaBladder cancerMaximal transurethral resection of bladder tumorEndpoint definitionsAlternative to radical cystectomyResection of bladder tumorCo-primary end pointsConcurrent systemic therapyMaximal transurethral resectionPhase II/III clinical trialsLocalized bladder cancerEvent-free survivalCooperative Oncology GroupBladder cancer researchStandard or Extended Lymphadenectomy for Muscle-Invasive Bladder Cancer
Lerner S, Tangen C, Svatek R, Daneshmand S, Pohar K, Skinner E, Schuckman A, Sagalowsky A, Smith N, Kamat A, Kassouf W, Plets M, Bangs R, Koppie T, Alva A, La Rosa F, Pal S, Kibel A, Canter D, Thompson I. Standard or Extended Lymphadenectomy for Muscle-Invasive Bladder Cancer. New England Journal Of Medicine 2024, 391: 1206-1216. DOI: 10.1056/nejmoa2401497.Peer-Reviewed Original ResearchMitochondrial reprogramming by activating OXPHOS via glutamine metabolism in African American patients with bladder cancer
Reddy K, Piyarathna D, Park J, Putluri V, Amara C, Kamal A, Xu J, Kraushaar D, Huang S, Jung S, Eberlin L, Johnson J, Kittles R, Ballester L, Parsawar K, Siddiqui M, Gao J, Gramer A, Bollag R, Terris M, Lotan Y, Creighton C, Lerner S, Sreekumar A, Kaipparettu B, Putluri N. Mitochondrial reprogramming by activating OXPHOS via glutamine metabolism in African American patients with bladder cancer. JCI Insight 2024, 9: e172336. PMID: 39253977, PMCID: PMC11385078, DOI: 10.1172/jci.insight.172336.Peer-Reviewed Original ResearchConceptsBladder cancerOxidative phosphorylationComponents of complex IComplex IElevated mitochondrial oxidative phosphorylationComprehensive RNA-seqReduced basal respirationActive oxidative phosphorylationMitochondrial oxidative phosphorylationDecreased tumor growthTumor growth potentialIncreased disease progressionMitochondrial respiration rateAfrican American patientsRNA-seqRace-specific differencesMitochondrial reprogrammingEuropean AmericansMetabolic rewiringOXPHOS activityBasal respirationGlutamine metabolismGLS1 expressionPreclinical studiesATP productionLong‐term outcomes of bladder‐sparing therapy vs radical cystectomy in BCG‐unresponsive non‐muscle‐invasive bladder cancer
Taylor J, Kamat A, O'Donnell M, Annapureddy D, Howard J, Tan W, McElree I, Davaro F, Yim K, Harrington S, Dyer E, Black A, Kanabur P, Roumiguié M, Lerner S, Black P, Raman J, Preston M, Steinberg G, Huang W, Li R, Packiam V, Woldu S, Lotan Y. Long‐term outcomes of bladder‐sparing therapy vs radical cystectomy in BCG‐unresponsive non‐muscle‐invasive bladder cancer. BJU International 2024 PMID: 39183466, DOI: 10.1111/bju.16509.Peer-Reviewed Original ResearchNon-muscle-invasive bladder cancerBladder-sparing therapyUpfront RCRadical cystectomyCohort of patientsBladder cancerBCG-unresponsive NMIBCRetrospective cohort of patientsProgression to MIBCUpfront radical cystectomyCancer-specific survivalInstitutional review board approvalMetastasis-free survivalFood and Drug Administration criteriaRate of recurrenceReview board approvalLong-term outcomesStatistically significant differenceNodal diseaseRe-resectionSystemic immunotherapyIntravesical chemotherapyOncological outcomesOverall survivalOncological riskBladder-sparing Therapy for Bacillus Calmette-Guérin–unresponsive Non–muscle-invasive Bladder Cancer: International Bladder Cancer Group Recommendations for Optimal Sequencing and Patient Selection
Li R, Hensley P, Gupta S, Al-Ahmadie H, Babjuk M, Black P, Brausi M, Bree K, Fernández M, Guo C, Horowitz A, Lamm D, Lerner S, Lotan Y, Mariappan P, McConkey D, Mertens L, Mir C, Ross J, O'Donnell M, Palou J, Pohar K, Steinberg G, Soloway M, Spiess P, Svatek R, Tan W, Taoka R, Buckley R, Kamat A. Bladder-sparing Therapy for Bacillus Calmette-Guérin–unresponsive Non–muscle-invasive Bladder Cancer: International Bladder Cancer Group Recommendations for Optimal Sequencing and Patient Selection. European Urology 2024 PMID: 39183090, DOI: 10.1016/j.eururo.2024.08.001.Peer-Reviewed Original ResearchNon-muscle-invasive bladder cancerInternational Bladder Cancer GroupBladder-sparing treatmentCarcinoma in situNadofaragene firadenovecRadical cystectomyBladder cancerOptimal selection of patientsAbsence of randomized trialsBladder-sparing therapySingle-agent chemotherapyBladder cancer groupSelection of patientsDevelopment of agentsPatient selectionSystemic toxicityCancer groupUnapproved agentsClinical trial participationPatient characteristicsRandomized trialsMitomycin CTumor attributesConsensus recommendationsCancer expertsCorrelative Analysis of ATM, RB1, ERCC2, and FANCC Mutations and Pathologic Complete Response After Neoadjuvant Chemotherapy in Patients with Muscle-invasive Bladder Cancer: Results from the SWOG S1314 Trial
Plimack E, Tangen C, Plets M, Kokate R, Xiu J, Nabhan C, Ross E, Grundy E, Choi W, Dinney C, Lee I, Fong M, Lucia M, Daneshmand S, Theodorescu D, Goldkorn A, Lerner S, Flaig T, McConkey D. Correlative Analysis of ATM, RB1, ERCC2, and FANCC Mutations and Pathologic Complete Response After Neoadjuvant Chemotherapy in Patients with Muscle-invasive Bladder Cancer: Results from the SWOG S1314 Trial. European Urology 2024, 86: 297-300. PMID: 39003201, PMCID: PMC11416320, DOI: 10.1016/j.eururo.2024.06.018.Peer-Reviewed Original ResearchMuscle-invasive bladder cancerCisplatin-based chemotherapyNeoadjuvant chemotherapyBladder cancerTumor samplesNeoadjuvant cisplatin-based chemotherapyResponse to NACClinical assessmentDose-dense methotrexateTiming of cystectomyPathological complete responseClinical trials of chemotherapyTrials of chemotherapyNational clinical trialNeoadjuvant gemcitabineBladder preservationComplete responseTumor specimensSurgical specimensMulticenter trialPatient selectionTreatment armsGene panelChemotherapyGene mutationsEfficacy of Intravesical Nadofaragene Firadenovec for Patients With Bacillus Calmette-Guérin–Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-Up From a Phase 3 Trial
Narayan V, Boorjian S, Alemozaffar M, Konety B, Shore N, Gomella L, Kamat A, Bivalacqua T, Montgomery J, Lerner S, Busby J, Poch M, Crispen P, Steinberg G, Schuckman A, Downs T, Mashni J, Lane B, Guzzo T, Bratslavsky G, Karsh L, Woods M, Brown G, Canter D, Luchey A, Lotan Y, Inman B, Williams M, Cookson M, Chang S, Sankin A, O’Donnell M, Sawutz D, Philipson R, Parker N, Yla-Herttuala S, Rehm D, Jakobsen J, Juul K, Dinney C. Efficacy of Intravesical Nadofaragene Firadenovec for Patients With Bacillus Calmette-Guérin–Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-Up From a Phase 3 Trial. Journal Of Urology 2024, 212: 74-86. PMID: 38704840, DOI: 10.1097/ju.0000000000004020.Peer-Reviewed Original ResearchConceptsNonmuscle-invasive bladder cancerPhase 3 trialBladder cancerFollow-upAdenoviral vector-based gene therapyProgression to muscle-invasive diseaseOpen-label phase 3 trialVector-based gene therapyCystectomy-free survivalMuscle-invasive diseaseMedian follow-upCarcinoma in situBladder preservationNadofaragene firadenovecOverall survivalGene therapyCytological assessmentTa/T1PatientsUS sitesCohortReceiving treatmentMonthsCancerHGRFONCOLOGIC OUTCOMES OF GEMCITABINE-DOCETAXEL COMBINATION INTRAVESICAL BLADDER SPARING THERAPY COMPARED TO UPFRONT RADICAL CYSTECTOMY IN BCG-UNRESPONSIVE NON-MUSCLE INVASIVE BLADDER CANCER
Annapureddy D, Taylor J, Howard J, Woldu S, Lotan Y, Tan W, Kamat A, McElree I, Packiam V, O'Donnell M, Facundo D, Li R, Yim K, Preston M, Harrington S, Dyer E, Raman J, Black A, Black P, Kanabur P, Lerner S, Roumiguié M, Steinberg G, Huang W. ONCOLOGIC OUTCOMES OF GEMCITABINE-DOCETAXEL COMBINATION INTRAVESICAL BLADDER SPARING THERAPY COMPARED TO UPFRONT RADICAL CYSTECTOMY IN BCG-UNRESPONSIVE NON-MUSCLE INVASIVE BLADDER CANCER. Urologic Oncology Seminars And Original Investigations 2024, 42: s52-s53. DOI: 10.1016/j.urolonc.2024.01.160.Peer-Reviewed Original ResearchNon-muscle invasive bladder cancerBladder-sparing therapyBCG-unresponsive diseaseBCG-unresponsive NMIBCMultinational cohort of patientsUpfront RCCancer-specific survivalInvasive bladder cancerRadical cystectomyOncological outcomesCohort of patientsAdequate BCGBCG therapyBCG-unresponsiveSalvage therapySpecific survivalBladder cancerMultinational cohortBCG-unresponsive NMIBC patientsAdequate BCG therapyBladder sparing therapyCombination intravesical therapyMaintenance BCG therapyNode positivity rateCompare oncologic outcomesDEVELOPMENT AND TESTING OF A CUSTOM NANOSTRING RNA CODESET FOR MUSCLE-INVASIVE BLADDER CANCER UTILIZING TCGA SUBTYPING (SWOG S1011)
Patel S, Anurag M, Lerner S, Lucia S, Meeks J, McConkey D, Kim J. DEVELOPMENT AND TESTING OF A CUSTOM NANOSTRING RNA CODESET FOR MUSCLE-INVASIVE BLADDER CANCER UTILIZING TCGA SUBTYPING (SWOG S1011). Urologic Oncology Seminars And Original Investigations 2024, 42: s31-s32. DOI: 10.1016/j.urolonc.2024.01.111.Peer-Reviewed Original ResearchMuscle-invasive bladder cancerSubtype callsLuminal papillaryRNA sequencingMIBC subtypesTumor subtypesMolecular subtypesSubtype classificationPatient classifierTCGA subtypesComprehensive genomic profilingResponse to chemotherapyFormalin-fixed paraffin-embedded (FFPEPatient biopsy tissueParaffin-embedded (FFPEWhole-transcriptome RNA sequencingTranscriptome RNA sequencingRNA-seqClinical outcomesBladder cancerBiopsy tissueHeterogeneous diseaseRNA-based classifiersRNA samplesSWOGThe IL6/JAK/STAT3 signaling axis is a therapeutic vulnerability in SMARCB1-deficient bladder cancer
Amara C, Kami Reddy K, Yuntao Y, Chan Y, Piyarathna D, Dobrolecki L, Shih D, Shi Z, Xu J, Huang S, Ellis M, Apolo A, Ballester L, Gao J, Hansel D, Lotan Y, Hodges H, Lerner S, Creighton C, Sreekumar A, Zheng W, Msaouel P, Kavuri S, Putluri N. The IL6/JAK/STAT3 signaling axis is a therapeutic vulnerability in SMARCB1-deficient bladder cancer. Nature Communications 2024, 15: 1373. PMID: 38355560, PMCID: PMC10867091, DOI: 10.1038/s41467-024-45132-2.Peer-Reviewed Original ResearchConceptsSignaling axisSMARCB1-deficient tumorsSMARCB1 deficiencyBladder cancerChromatin accessibilitySTAT3 inhibitorTumor growthSMARCB1 lossPatient-derived xenograft modelsCell line-derived xenograftsTherapeutic vulnerabilitiesTarget pathwaysReduced tumor growthIncreased tumor growthCell linesIn vivo modelsSTAT3Gene signatureSMARCB1TTI-101Solid tumorsXenograft modelClinical evaluationDisease progressionTumorMultiomics profiling of urothelial carcinoma in situ reveals CIS-specific gene signature and immune characteristics
Anurag M, Strandgaard T, Kim S, Dou Y, Comperat E, Al-Ahmadie H, Inman B, Taber A, Nordentoft I, Jensen J, Dyrskjøt L, Lerner S. Multiomics profiling of urothelial carcinoma in situ reveals CIS-specific gene signature and immune characteristics. IScience 2024, 27: 109179. PMID: 38439961, PMCID: PMC10910238, DOI: 10.1016/j.isci.2024.109179.Peer-Reviewed Original ResearchCarcinoma in situCarcinoma in situ lesionsUrothelial carcinoma in situPapillary tumorsAggressive phenotypeAssociated with carcinoma in situNon-muscle-invasive bladder cancerCarcinoma in situ samplesPD-1-positive cellsImmune marker expressionBladder cancerImmunological landscapeMarker expressionTumorGene signatureMutational heterogeneityImmune characteristicsMutated genesExpression signaturesTargeting mTORHigher expressionTime pointsMutation analysisMultiomic profilingLesionsCorrelation of urinary comprehensive genomic profile with risk of recurrence of BCG-unresponsive non-muscle invasive bladder cancer treated with atezolizumab in SWOG S1605.
St-Laurent M, Plets M, Black P, Singh P, McConkey D, Lucia S, Koshkin V, Stratton K, Bivalacqua T, Kassouf W, Porten S, Bangs R, Tangen C, Thompson I, Meeks J, Caruso V, Phillips K, Bicocca V, Levin T, Lerner S. Correlation of urinary comprehensive genomic profile with risk of recurrence of BCG-unresponsive non-muscle invasive bladder cancer treated with atezolizumab in SWOG S1605. Journal Of Clinical Oncology 2024, 42: 529-529. DOI: 10.1200/jco.2024.42.4_suppl.529.Peer-Reviewed Original ResearchNon-muscle invasive bladder cancerEvent-free survivalEvent-free survival probabilityComprehensive genomic profilingLow-risk patientsGenomic profilingBCG-unresponsiveRisk scoreBladder cancerHigh riskMolecular response to treatmentImmune checkpoint inhibitionCycles of therapyInvasive bladder cancerEarly treatment intensificationRisk of progressionCycles of treatmentHigh gradeResponse to treatmentTime pointsMolecular responseHG recurrenceIntravenous atezolizumabPersistent CISBladder preservationPredicting clinical outcomes in the S1314-COXEN trial using a multimodal deep learning model integrating histopathology, cell types, and gene expression.
Faltas B, Bai Z, Osman M, Brendel M, Tangen C, Flaig T, Thompson I, Plets M, Lucia M, Theodorescu D, Gustafson D, Daneshmand S, Meeks J, Choi W, Dinney C, Elemento O, Lerner S, McConkey D, Wang F. Predicting clinical outcomes in the S1314-COXEN trial using a multimodal deep learning model integrating histopathology, cell types, and gene expression. Journal Of Clinical Oncology 2024, 42: 533-533. DOI: 10.1200/jco.2024.42.4_suppl.533.Peer-Reviewed Original ResearchMuscle-invasive bladder cancerResponse to NACNeoadjuvant chemotherapyPathological response to NACOutcomes of neoadjuvant chemotherapyResponse to neoadjuvant chemotherapyPrediction of response to neoadjuvant chemotherapyCell typesNAC responseDevelopment of precision therapiesOptimize treatment outcomesGene set analysisPredicting cell typesGemcitabine-cisplatinRNA expression dataTumor microenvironmentPathological responseBladder cancerClinical outcomesGene expression vectorPrecision therapyClinical trialsTreatment outcomesStromal cellsBasal differentiationDescribing the genomic landscape of bladder cancer histologic subtypes.
Talukder R, Berg R, Huang M, Nepomucino V, Stoppler M, Makrakis D, Yen A, Mims M, Lerner S, Woldu S, Lotan Y, Yu E, Khaki A, Aragon-Ching J, Grivas P. Describing the genomic landscape of bladder cancer histologic subtypes. Journal Of Clinical Oncology 2024, 42: 680-680. DOI: 10.1200/jco.2024.42.4_suppl.680.Peer-Reviewed Original ResearchHistological subtypes of bladder cancerSquamous cell differentiationSubtypes of bladder cancerSmall cell/neuroendocrineHistological subtypesBladder cancerGenomic alterationsOverall cohortPD-L1-positive statusDiagnosis of bladder cancerAssociated with poor prognosisTumor mutational burdenGenomic landscapeCancer histological subtypesGenomic alteration patternsClinical trial designCopy number variantsMSI-high statusKruskal-Wallis testPD-L1Immunotherapy biomarkersERBB2 amplificationMutational burdenMedian ageTherapy resistanceEnsuring Successful Biomarker Studies in Bladder Preservation Clinical Trials for Non-muscle Invasive Bladder Cancer
McConkey D, Baumann B, Greenberg S, DeGraff D, Delacroix S, Efstathiou J, Foster J, Groshen S, Kadel E, Khani F, Kim W, Lerner S, Levin T, Liao J, Milowsky M, Meeks J, Miyamoto D, Mouw K, Pietzak E, Solit D, Sundi D, Tawab-Amiri A, West P, Wobker S, Wyatt A, Apolo A, Black P. Ensuring Successful Biomarker Studies in Bladder Preservation Clinical Trials for Non-muscle Invasive Bladder Cancer. Bladder Cancer 2024, 10: 1-8. PMID: 38993535, PMCID: PMC11181871, DOI: 10.3233/blc-230082.Peer-Reviewed Original Research
2023
Genomic Profiling of Urothelial Carcinoma <I>in Situ</I> of the Bladder
Anurag M, Strandgaard T, Kim S, Comperat E, Al-Ahmadie H, Inman B, Dyrskjot L, Lerner S. Genomic Profiling of Urothelial Carcinoma in Situ of the Bladder. EMJ Urology 2023, 11: 41-42. DOI: 10.33590/emjurol/10306009.Peer-Reviewed Original ResearchCarcinoma in situUrothelial carcinoma in situCarcinoma in situ lesionsPapillary tumorsWhole-exome sequencingBladder cancerInvasive cancerMolecular subtypesT cellsFFPE samplesAssociated with carcinoma in situPresence of cytotoxic T cellsProgrammed cell death protein 1Formalin-fixed paraffin-embedded (FFPE) tumorsAssociated with invasive cancerCarcinoma in situ samplesCell death protein 1Detecting carcinoma in situExome sequencingLevels of immune cellsRNA sequencingProbability of disease progressionHigh-grade lesionsRegulatory T cellsCytotoxic T cells