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

*Cystectomy Humans *Neoadjuvant Therapy Neoplasm Staging Treatment Outcome Urinary Bladder Neoplasms/*drug therapy/pathology/*surgery

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.

Animals Biological Availability Clinical Trials as Topic Flavonoids/pharmacology/*therapeutic use Flavonols/pharmacology/*therapeutic use Humans Inhibitory Concentration 50 Kaempferols/pharmacology/*therapeutic use Male Models Animal Prostatic Neoplasms/*drug therapy Urinary Bladder Neoplasms/*drug therapy bladder cancer fisetin kaempferol myricetin prostate cancer

Administration Intravesical BCG Vaccine/*adverse effects/*therapeutic use Humans Meta-Analysis as Topic Randomized Controlled Trials as Topic *Systematic Reviews as Topic Urinary Bladder Neoplasms/*drug therapy

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

Carcinoma Transitional Cell/*drug therapy Humans Prognosis Receptors Fibroblast Growth Factor/*antagonists & inhibitors Urinary Bladder Neoplasms/*drug therapy Bladder cancer Fgfr FGFR inhibitors Fgfr3 Progression Urothelial carcinoma

Adjuvants Immunologic/*administration & dosage Administration Intravesical BCG Vaccine/*administration & dosage Humans *Lymphocytes Tumor-Infiltrating Treatment Outcome Urinary Bladder Neoplasms/*drug therapy/immunology/*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

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 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.

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

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

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 Humans Infusions Intra-Arterial Meta-Analysis as Topic Systematic Reviews as Topic Urinary Bladder Neoplasms/*drug therapy