Adjuvants Immunologic/administration & dosage Administration Intravesical Antibiotics Antineoplastic/administration & dosage/adverse effects Antimetabolites Antineoplastic/*administration & dosage/adverse effects BCG Vaccine/administration & dosage Bias Cause of Death Confidence Intervals Deoxycytidine/administration & dosage/adverse effects/*analogs & derivatives Disease Progression Drug Administration Schedule Humans Mitomycin/administration & dosage/adverse effects Neoplasm Recurrence Local/*drug therapy/mortality/prevention & control Randomized Controlled Trials as Topic Saline Solution/administration & dosage Urinary Bladder Neoplasms/*drug therapy/mortality/pathology/prevention & control Gemcitabine

Anti-Bacterial Agents/therapeutic use Antibiotic Prophylaxis Humans Meta-Analysis as Topic Postoperative Complications/drug therapy Systematic Reviews as Topic *Urinary Bladder Neoplasms/drug therapy/surgery *Urinary Tract Infections/drug therapy/prevention & control Antibiotic resistance Antibiotics Antimicrobial stewardship Bacteriuria Endourological surgery Guideline Recommendation Transitional cell carcinoma Urothelium cell carcinoma

Antineoplastic Agents Immunological/*therapeutic use Carcinoma Transitional Cell/*drug therapy Humans Immunotherapy/*adverse effects/methods Network Meta-Analysis Salvage Therapy/*methods Urinary Bladder Neoplasms/*drug therapy Rct Uc Ucb adverse events chemotherapy immunotherapy network meta-analyses second-line

Administration Intravesical Antibiotics Antineoplastic/*administration & dosage Antimetabolites Antineoplastic/*administration & dosage Deoxycytidine/administration & dosage/*analogs & derivatives Humans Mitomycin/*administration & dosage Neoplasm Invasiveness Randomized Controlled Trials as Topic Urinary Bladder Neoplasms/*drug therapy/pathology Gemcitabine Bladder cancer Meta-analysis Mitomycin Systematic evaluation

Administration Intravesical Antibiotics Antineoplastic/administration & dosage/*therapeutic use BCG Vaccine Carcinoma Transitional Cell/*drug therapy Humans Mitomycin/administration & dosage/*therapeutic use Randomized Controlled Trials as Topic Treatment Outcome Urinary Bladder Neoplasms/*drug therapy

Adjuvants Immunologic/therapeutic use Administration Intravesical Consensus Humans Neoplasm Invasiveness Neoplasm Recurrence Local/drug therapy *Urinary Bladder Neoplasms/drug therapy Bladder neoplasms Expert consensus Intravesical therapy

Antineoplastic Agents Alkylating/pharmacology/*therapeutic use Cyclophosphamide/pharmacology/*therapeutic use Female Humans Male Survival Analysis Urinary Bladder Neoplasms/*drug therapy/mortality Cyclophosphamide Hematuria Systematic review Urinary bladder neoplasms

Adjuvants Immunologic/adverse effects Administration Intravesical BCG Vaccine/adverse effects Humans *Urinary Bladder Neoplasms/drug therapy *Urology Antibiothérapie Antibiotic therapy BCG therapy BCG thérapie Bladder Carcinome urothélial Complications Endovesical instillations Instillations endovésicales Nmibc Tvnim Urothelial carcinoma Vessie

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.

Antineoplastic Agents/*therapeutic use Chemotherapy Adjuvant/*statistics & numerical data *Cystectomy Global Health Guideline Adherence/statistics & numerical data Humans Models Statistical Neoadjuvant Therapy/*statistics & numerical data Neoplasm Invasiveness Practice Guidelines as Topic Practice Patterns Physicians'/*statistics & numerical data Urinary Bladder Neoplasms/*drug therapy/pathology/surgery

Antihypertensive Agents/*adverse effects/therapeutic use Disease Susceptibility Dose-Response Relationship Drug Humans Hypertension/complications/drug therapy/etiology Kidney Neoplasms/*epidemiology/*etiology Odds Ratio Publication Bias Risk Assessment Risk Factors Urinary Bladder Neoplasms/*epidemiology/*etiology antihypertensive medications bladder cancer kidney cancer meta-analysis risk interest.

Chemotherapy Adjuvant *Cystectomy/methods Humans Neoadjuvant Therapy Smoking/*adverse effects Survival Rate Treatment Outcome Urinary Bladder Neoplasms/drug therapy/*mortality/*surgery cigarette smoking cystectomy recurrence survival urinary bladder neoplasms

Administration Intravesical Drug Therapy/instrumentation Humans Neoplasm Invasiveness Treatment Outcome Urinary Bladder Neoplasms/*drug therapy/pathology Emda Nmibc NMIBC Carcinome de la vessie TURBT EMDA RITE Synergo Rite Synergo Turbt Urothelial carcinoma

Antineoplastic Combined Chemotherapy Protocols/*therapeutic use Chemotherapy Adjuvant *Cystectomy/methods Humans Neoadjuvant Therapy Neoplasm Invasiveness Survival Rate Urinary Bladder Neoplasms/*drug therapy/mortality/pathology/*surgery Muscle-invasive bladder cancer Neoadjuvant chemotherapy Overall survival Radical cystectomy

Androgen Antagonists/*therapeutic use Humans Male Observational Studies as Topic Prostatic Neoplasms/*drug therapy Risk Assessment Urinary Bladder Neoplasms/epidemiology/*prevention & control Androgen deprivation therapy Bladder cancer Pharmacoepidemiology Prostate cancer Systematic review

Antibodies Monoclonal/adverse effects/therapeutic use Antibodies Monoclonal Humanized/adverse effects/therapeutic use Antineoplastic Agents Immunological/*therapeutic use B7-H1 Antigen/*antagonists & inhibitors Clinical Trials Phase III as Topic Humans Network Meta-Analysis Programmed Cell Death 1 Receptor/*antagonists & inhibitors Salvage Therapy/*methods Survival Analysis Treatment Outcome Urinary Bladder Neoplasms/*drug therapy/*secondary PD-1 inhibitor PDL-1 inhibitor atezolizumab pembrolizumab urothelial bladder cancer

Administration Intravesical Antineoplastic Agents/administration & dosage Combined Modality Therapy Cystectomy/methods Humans Randomized Controlled Trials as Topic Saline Solution/*administration & dosage/adverse effects Therapeutic Irrigation/adverse effects/methods Treatment Outcome Urethra Urinary Bladder Neoplasms/drug therapy/surgery/*therapy Continuous saline bladder irrigation Meta-analysis Non-muscle invasive bladder cancer Randomized controlled trials Transurethral resection of bladder tumors

Diabetes Mellitus Type 2/*drug therapy Dose-Response Relationship Drug Humans Hypoglycemic Agents/*adverse effects Incidence Observational Studies as Topic Pioglitazone/*adverse effects Risk Factors Urinary Bladder Neoplasms/*chemically induced

Female Humans Male Prospective Studies *Quality of Life Urinary Bladder Neoplasms/drug therapy/*psychology/radiotherapy Bladder cancer Chemotherapy Muscle-invasive bladder cancer Quality of life Urothelial cancer 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.

Diabetes Mellitus Type 2/complications/drug therapy Humans Hypoglycemic Agents/*adverse effects/therapeutic use Odds Ratio Pioglitazone/*adverse effects/therapeutic use Randomized Controlled Trials as Topic Risk Assessment Risk Factors Time Factors Urinary Bladder Neoplasms/*etiology Bladder cancer dose-response relationship meta-analysis pioglitazone