Adult Aged Aged 80 and over B7-H1 Antigen/genetics/*immunology Female Humans Immune Checkpoint Inhibitors/*administration & dosage *Immunotherapy Male Middle Aged Programmed Cell Death 1 Receptor/genetics/*immunology Progression-Free Survival Randomized Controlled Trials as Topic Treatment Outcome Urinary Bladder Neoplasms/genetics/immunology/mortality/*therapy efficacy immunotherapy meta-analysis safety urothelial cancer this study.

Guidelines as Topic Humans Immunotherapy/*methods Societies Medical/*standards Urinary Bladder Neoplasms/*drug therapy antineoplastic protocols immunotherapy urinary bladder neoplasms urologic neoplasms Pfizer AstraZeneca Nektar Seattle Genetics DragonFly Therapeutics Non-CME services: Genentech AstraZeneca Merck Seattle Genetics Contracted research: Genentech Merck AstraZeneca Nektar Seattle Genetics Immunomedics. PCB─Consulting fees: AbbVie Asieris Pharmaceuticals Astellas AstraZeneca Bayer Biosyent Bristol-Myers Squibb EMD Serono Ferring Fergene H3 Biomedicine Janssen Merck Roche Sanofi TerSera Urogen Contracted research: iProgen. MTC─Consulting fees: Pfizer EMD Serono AstraZeneca Exelixis Eisai Seattle Genetics Astellas Contracted research: Exelixis Pfizer/EMD Serono Janssen Apricity Health. GSD─Participant/unpaid volunteer: HealthVibe focus group 2020. MDG─Consulting fees: Inovio NuMab Janssen Merck GlaxoSmithKline Genentech Bristol-Myers Squibb Seattle Genetics Dracen Dragonfly Astellas Novartis Pfizer AstraZeneca Incyte Dendreon Eli Lilly EMD Serono Aileron Therapeutics Ownership interest: Rappta Therapeutics NPI: 1639140668. PG─Consulting fees: AstraZeneca Dyania Health EMD Serono Immunomedics Janssen Merck Mirati Therapeutics Genentech Pfizer Seattle Genetics Contracted Research: Bavarian Nordic Bristol-Myers Squibb Clovis Oncology Debiopharm Immunomedics Pfizer Merck QED Therapeutics GlaxoSmithKline Kure It Cancer Research Mirati Therapeutics. SG─Consulting fees: Merck Bristol-Myers Squibb Janssen Seattle Genetics AstraZeneca Contracted research: Bristol-Myers Squibb Pfizer Non-CME services: Exelixis. CJH─Consulting fees: Astellas Bristol-Myers Squibb Genentech Merck Eisai Seattle Genetics 2bPrecise Non-CME services: Astellas Bristol-Myers Squibb Genentech Eisai Seattle Genetics. AMK─Consulting fees: Abbott Molecular Arquer ArTara Asieris AstraZeneca BioClin Therapeutics Bristol-Myers Squibb Cepheid Cold Genesys Eisai Engene Inc. Ferring FerGene Imagin Janssen MDxHealth Medac Merck Pfizer Photocure ProTara Roviant Seattle Genetics Sessen Bio Theralase TMC Innovation US Biotest Contracted research: Adolor Bristol-Myers Squibb FKD Industries Heat Biologics Merck Photocure SWOG/NIH SPORE AIBCCR Clinical trials: FKD Merck Bristol-Myers Squibb Photocure SWOG Adolor Heat Biologics Laboratory research: NIH SPORE AIBCCR Educational grant: CEC Oncology Editorial board: European Urology Oncology Journal of Urology UroToday President of organization: International Bladder Cancer Network (IBCN) International Bladder Cancer Group (IBCG) IP Rights: CyPRIT (Cytokine Predictors of Response to Intravesical Therapy) Joint with UT MD Anderson Cancer Center. LPL─Consulting fees: Pfizer Advisory Nursing board 2018 Lecture/Speaker/Expert Panel: ASCO Bladder Program 2019 Pfizer learning day 2019 ASCO Bladder Program Panel Member and Faculty 2019 Pfizer Learning Day Speaker 2019 BCAN Webinar Faculty 11/2020. JJM─Consulting fees: AstraZeneca Ferring Janssen Nucleix Foundation Medicine Contracted research: Epizyme Tesaro Abbvie Teaching an endoscopy course: Olympus. ERP─Consulting fees: AstraZeneca Infinity Pharma Pfizer Flatiron Genentech Merck Seattle Genetics Contracted research: Astellas Bristol-Myers Squibb Genentech Merck. JER─Consulting fees: Merck Bristol-Myers Squibb AstraZeneca Astellas Seattle Genetics Boehringer Ingelheim Bayer Pfizer Roche/Genentech Mirati QED Therapeutics Janssen Pharmacyclics GlaxoSmithKline Contracted research/Clinical trial funding: Seattle Genetics Astellas Roche/Genentech Bayer AstraZeneca QED Therapeutics. NS─Consulting fees: Amgen Astellas AstraZeneca Bayer Bristol-Myers Squibb Dendreon Fergene Ferring Janssen Merck Myovant Nymox Pfizer Sanofi/Genzyme Sesen Bio Sun Pharma Tolmar. GDS─Consulting fees: Merck Janssen Ferring Bristol-Myers Squibb Pfizer Genentech Epivax Oncology AstraZeneca Fidia Cold Genesys EnGene Bio Aduro Biotech Dendreon FKD Therapies CiClomed Seattle Genetics Urogen PhotoCure. SITC staff: SMW—Shares owned: Pacific Biosciences Editas Medicine EG AK BL LL─Nothing to disclose.

Biomarkers Tumor/*urine DNA Neoplasm/*urine Humans RNA Neoplasm/*urine Urinary Bladder Neoplasms/*genetics/*urine Watchful Waiting Biomarkers Bladder Genetic Surveillance

5-ala 5-aminolaevulinic acid Hal Pdd accuracy meta-analysis bladder cancer blue light cystoscopy cystoscopy hexaminolevulinate narrow band imaging photodynamic diagnosis fluorescence consultant for Janssen Ferring Photocure Taris Spectrum Pacific Edge QED Abbvie Johnson & Johnson Seattle Genetics Nucleix Aduro and BMS. Ashish Kamat is is a consultant for Photocure. Mihir Desai is a consultant for Procept Biorobotics and Auris Surgical. Yair Lotan is a consultant for Photocure. Angela Smith is an investigator for Urogen and a consultant for FerGene Urogen and Merck.

Biomarkers Tumor/genetics Carcinoma/genetics Gene Expression/genetics Gene Expression Profiling/methods Gene Expression Regulation Neoplastic/genetics Humans Neoplasm Recurrence Local/genetics Odds Ratio Prognosis RNA Circular/*genetics Survival Analysis Transcriptome/genetics Urinary Bladder/pathology Urinary Bladder Neoplasms/*genetics/metabolism bladder cancer circular RNA meta-analysis

Case-Control Studies Humans *Polymorphism Single Nucleotide Promoter Regions Genetic Urinary Bladder Neoplasms/*genetics Vascular Endothelial Growth Factor A/*genetics Bladder cancer Meta-analysis Polymorphism Vascular endothelial growth factor competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

*Biomarkers Tumor Carcinoma Transitional Cell/*genetics/mortality/pathology *DNA Methylation Humans Neoplasm Invasiveness Prognosis Risk Assessment Survival Rate Urinary Bladder Neoplasms/*genetics/mortality/pathology Biomarkers Dna High-risk non–muscle-invasive bladder cancer Methylation Prognostic markers Systematic review molecular markers

Arylamine N-Acetyltransferase/*genetics Asian People/genetics Humans *Polymorphism Single Nucleotide Smoking/epidemiology Urinary Bladder Neoplasms/epidemiology/ethnology/*genetics White People/genetics Bladder cancer Meta-analysis N-acetyltransferase 2 Polymorphism competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Biomarkers Tumor/*metabolism Humans RNA Long Noncoding/*metabolism Urinary Bladder Neoplasms/*diagnosis/*genetics/pathology bladder cancer lncRNAs meta-analysis non-invasive diagnosis

Biomarkers/urine DNA Mutational Analysis DNA Neoplasm/*urine Disease Progression Humans Mutation Neoplasm Recurrence Local/*diagnosis/genetics/*urine Sensitivity and Specificity Urinary Bladder Neoplasms/*diagnosis/genetics/*urine #BladderCancer #blcsm biomarkers molecular diagnostics urinary bladder neoplasms urine analysis Amsterdam UMC location VUmc. J. Bosschieter R.D.M. Steenbergen and J.A. Nieuwenhuijzen are inventors on patent(s) related to the work.

*DNA Methylation DNA Neoplasm/*metabolism Humans Prognosis Urinary Bladder Neoplasms/*diagnosis/*genetics Biomarker Bladder cancer DNA methylation Overall survival Progression-free survival

B7-H1 Antigen/*metabolism Biomarkers Tumor/metabolism Carcinoma Transitional Cell/metabolism/*mortality/pathology Cell Membrane/metabolism Gene Expression Regulation Neoplastic Humans Neoplasm Staging Prognosis Survival Analysis *Up-Regulation Urinary Bladder Neoplasms/metabolism/*mortality/pathology Biomarker Meta-analysis Pd-l1 Urothelial carcinoma

Asian People/genetics Carcinoma Renal Cell/genetics Female Genetic Association Studies/*methods Genetic Predisposition to Disease Humans Kidney Neoplasms/genetics Male *Polymorphism Single Nucleotide Prostatic Neoplasms/genetics Urinary Bladder Neoplasms/genetics Urogenital Neoplasms/*genetics Vascular Endothelial Growth Factor A/*genetics Meta-analysis Polymorphism Urologic neoplasms Vascular endothelial growth factors

*Genetic Association Studies *Genetic Predisposition to Disease Genotype Glutathione Transferase/*genetics Humans Odds Ratio *Polymorphism Genetic Publication Bias Risk Urinary Bladder Neoplasms/*genetics Bladder cancer Gstm1 Gstp1 Gstt1 Gene polymorphism Meta-analysis PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER’S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

*DNA Methylation Disease Progression Female Genes APC/*physiology Humans Male *Promoter Regions Genetic *Urinary Bladder Neoplasms/genetics/pathology/urine

Antigenic Variation Antigens Neoplasm/*genetics Asian People GPI-Linked Proteins/genetics *Genetic Predisposition to Disease Humans Male Neoplasm Proteins/*genetics Polymorphism Single Nucleotide Urinary Bladder Neoplasms/*genetics White People

Carcinogens Environmental/adverse effects Gene-Environment Interaction Humans Incidence Occupational Exposure/adverse effects Prevalence Risk Assessment Risk Factors Smoking/adverse effects/epidemiology Time Factors Urinary Bladder Neoplasms/diagnosis/*epidemiology/genetics/mortality Bladder Cancer Epidemiology Urothelial

Arylamine N-Acetyltransferase/*genetics Genotype Humans Isoenzymes/*genetics Phenotype Polymorphism Genetic Urinary Bladder Neoplasms/*enzymology/*genetics N-Acetyltransferase Nat1 genetic polymorphism meta-analysis smoking systematic review urinary bladder cancer

Alleles Case-Control Studies *Genetic Predisposition to Disease Genotype Glutathione Transferase/*genetics Humans Odds Ratio *Polymorphism Genetic Publication Bias Risk Urinary Bladder Neoplasms/epidemiology/*genetics Gstm1 Gstt1 bladder cancer polymorphism

Epirubicin/*therapeutic use Female Humans Immunotherapy/*methods Male Mitomycin/*therapeutic use *Mycobacterium bovis Urinary Bladder Neoplasms/immunology/pathology/*therapy Bacillus Calmette–Guérin Consistency Epirubicin Gemcitabine Heterogeneity Interferon-Alpha Intravesical instillation therapies Mitomycin C Pairwise/network meta-analysis Tumor progression Tumor recurrence