Humans Mitomycin/therapeutic use Antibiotics Antineoplastic BCG Vaccine/therapeutic use *Non-Muscle Invasive Bladder Neoplasms Neoplasm Recurrence Local/drug therapy *Urinary Bladder Neoplasms/pathology Administration Intravesical Neoplasm Invasiveness Bladder cancer Device-assisted Emda Intravesical drug administration Nmibc

Aged Antineoplastic Combined Chemotherapy Protocols/*therapeutic use Carcinoma Transitional Cell/*drug therapy/*pathology Female Humans Immune Checkpoint Inhibitors/*therapeutic use Liver Neoplasms/secondary Male Middle Aged Survival Analysis Urinary Bladder Neoplasms/*drug therapy/*pathology bladder cancer immune checkpoint inhibitors immunotherapy meta-analysis urothelial carcinoma

*Antineoplastic Agents/adverse effects *Carcinoma Transitional Cell/drug therapy Humans Mutation Receptor ErbB-2 Trastuzumab/adverse effects *Urinary Bladder Neoplasms/drug therapy Erbb2 Her2 Metastatic bladder cancer Metastatic urothelial cancer Targeted treatment

Humans Administration Intravesical Antibiotics Antineoplastic/administration & dosage Hematuria/drug therapy *Mitomycin/administration & dosage Prospective Studies Quality of Life Treatment Outcome *Urinary Bladder Neoplasms/drug therapy/pathology/surgery

Antineoplastic Combined Chemotherapy Protocols/therapeutic use *Carcinoma Transitional Cell/pathology Cisplatin/therapeutic use Cystectomy Humans Muscles/pathology Neoadjuvant Therapy Neoplasm Invasiveness *Urinary Bladder Neoplasms/pathology Bladder cancer Muscle-invasive Urothelial from MSD and BMS and Speaker and Other from AstraZecena. BPV reports Advisory Board Speaker and Other from Astellas Roche BMS and Merk-Pfizer Advisory Board and Other from Ipsen Advisory Board and Speaker from EUSA and MSD and Advisory Board from Sanofi. IPF report Advisory Board Speaker and Other from Pfizer Speaker and Other from Ipsen and Roche Advisory Board from EUSA and BMS and Speaker from Novartis and MSD. OFC reports Advisory Board and Speaker from Ipsen and Astellas Advisory Board from BMS and Pfizer-Merck and Speaker from AstraZeneca. AGA has received research funding from Astellas travel grants from Astellas Jansen Sanofi BMS Roche Pfizer and Ipsen and honoraria for speaker engagements advisory boards and continuous medical education from Janssen Astellas Sanofi Bayer Roche Ipsen BMS MSD Pfizer Eusa Pharma Eisai and AstraZeneca. JAA reports honoraria from Astellas Pfizer and BMS conulting or advisory role from Pfizer Astellas Janssen-Cilag MSD Oncology BMS Merck AstraZeneca Bayer and Eisai and Research Funding from BMS. RMB SVE CCD and MDS have nothing to disclose.

Autoantigens Biomarkers Tumor/genetics/metabolism Gene Expression Regulation Neoplastic Humans Procollagen-Lysine 2-Oxoglutarate 5-Dioxygenase/genetics/metabolism Prognosis *Urinary Bladder Neoplasms/pathology Bladder cancer Meta-analysis Microarray datasets Overall survival Prognostic biomarker

Antineoplastic Combined Chemotherapy Protocols/adverse effects Bayes Theorem *Carcinoma Transitional Cell/drug therapy/surgery Humans Network Meta-Analysis *Urinary Bladder Neoplasms/drug therapy/surgery Ici Pd-1 Pd-l1 adjuvant therapy chemotherapy urothelial carcinoma

Administration Intravesical *Antineoplastic Agents/therapeutic use BCG Vaccine/therapeutic use Humans Neoplasm Recurrence Local Quality of Life *Urinary Bladder Neoplasms/drug therapy Bacillus Calmette–Guérin bladder cancer chemotherapy health-related quality of life hyperthermia immunotherapy intravesical therapy non-muscle invasive bladder cancer urothelial carcinoma

Adult Aged Aged 80 and over Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use B7-H1 Antigen/antagonists & inhibitors Carcinoma/*drug therapy/immunology/mortality/pathology Clinical Decision-Making Female Humans Immune Checkpoint Inhibitors/adverse effects/*therapeutic use Male Middle Aged Patient Selection Progression-Free Survival Time Factors Urinary Bladder Neoplasms/*drug therapy/immunology/mortality/pathology Urothelium/*drug effects/immunology/pathology Immune-checkpoint inhibitor Meta-analysis Programmed death-ligand 1 Urothelial carcinoma interests/personal relationships which may be considered as potential competing interests: The authors certify that all conflicts of interest including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the article are listed as follows: Shahrokh Shariat owns or co-owns the following patents: methods to determine prognosis after therapy for prostate cancer. Granted 2002-09-06. Methods to determine prognosis after therapy for bladder cancer. Granted 2003-06-19. Prognostic methods for patients with prostatic disease. Granted 2004-08-05. Soluble Fas: urinary marker for the detection of bladder transitional cell carcinoma. Granted 2010-07-20. He has a consulting or advisory role for the following: Astellas Astra Zeneca Bayer BMS Cepheid Ferring Ipsen Jansen Lilly MSD Olympus Pfizer Pierre Fabre Roche Sanochemia Sanofi Takeda Urogen and Wolff. All remaining authors have declared no conflicts of interest.

Antineoplastic Combined Chemotherapy Protocols/*therapeutic use Carcinoma Transitional Cell/*drug therapy/pathology Clinical Trials Phase II as Topic Clinical Trials Phase III as Topic Humans Neoplasm Metastasis Neoplasm Staging Practice Guidelines as Topic Randomized Controlled Trials as Topic Urinary Bladder Neoplasms/*drug therapy/pathology Immune checkpoint inhibitors Platinum-based chemotherapy Survival outcomes Treatment guidelines Urothelial carcinoma funded this work. MK PK and SD are employees of Evidera.

Antineoplastic Agents/*therapeutic use Biomarkers Tumor/*blood Humans Male Neoadjuvant Therapy/*methods Prognosis Urinary Bladder Neoplasms/blood/drug therapy/*pathology Biomarkers Bladder cancer Nac Neoadjuvant chemotherapy Systematic review Ucb

Administration Intravesical Antineoplastic Agents/*administration & dosage/adverse effects Clinical Trials as Topic Disease Progression Humans Neoplasm Metastasis *Neoplasm Recurrence Local Network Meta-Analysis Progression-Free Survival Risk Assessment Risk Factors Time Factors Urinary Bladder Neoplasms/*drug therapy/mortality/pathology

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

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

Antineoplastic Combined Chemotherapy Protocols/*therapeutic use Chemotherapy Adjuvant/methods Cisplatin/therapeutic use Clinical Decision-Making/methods *Cystectomy Disease-Free Survival Female Humans Male Neoadjuvant Therapy/methods Neoplasm Recurrence Local/*epidemiology/pathology/prevention & control Neoplasm Staging Patient Selection *Sex Factors Urinary Bladder/pathology/surgery Urinary Bladder Neoplasms/mortality/pathology/*therapy Adjuvant chemotherapy Bladder cancer Gender Meta-analysis Neoadjuvant chemotherapy

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

Antineoplastic Combined Chemotherapy Protocols/*therapeutic use Carcinoma Transitional Cell/immunology/mortality/pathology/*therapy Chemotherapy Adjuvant/methods/statistics & numerical data Clinical Trials Phase I as Topic Clinical Trials Phase II as Topic Cystectomy Disease-Free Survival Follow-Up Studies Humans Immune Checkpoint Inhibitors/*therapeutic use Muscle Smooth/pathology/surgery Neoadjuvant Therapy/*methods/statistics & numerical data Neoplasm Invasiveness/pathology Prospective Studies Treatment Outcome Urinary Bladder/pathology/surgery Urinary Bladder Neoplasms/immunology/mortality/pathology/*therapy Bladder cancer Immune checkpoint inhibitors Immunotherapy Neoadjuvant

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

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.