Bladder Cancer Checkpoint Inhibitors Chemotherapy Immunotherapy Urothelial Cancer

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

bladder cancer checkpoint inhibitors chemotherapy immunotherapy radical cystectomy design of the study in the collection analyses or interpretation of data in the writing of the manuscript or in the decision to publish the results.

Cisplatin/adverse effects Humans *Immunotherapy/adverse effects/methods *Muscles/pathology *Neoadjuvant Therapy/adverse effects Neoplasm Staging *Urinary Bladder Neoplasms/drug therapy/pathology/therapy chemoimmunotherapy immunotherapy meta-analysis muscle-invasive bladder cancer (MIBC) neoadjuvant commercial or financial relationships that could be construed as a potential conflict of interest.

Humans Immunotherapy Inflammation Prognosis Progression-Free Survival *Urinary Bladder Neoplasms

*Carcinoma Transitional Cell/drug therapy Female Humans Immune Checkpoint Inhibitors/therapeutic use Immunotherapy *Lung Neoplasms/pathology Male Platinum/therapeutic use Programmed Cell Death 1 Receptor *Urinary Bladder Neoplasms/drug therapy

*Carcinoma Transitional Cell/drug therapy/pathology Cisplatin Female Humans Male *Urinary Bladder Neoplasms/drug therapy/pathology *Urology *Bladder cancer *European Association of Urology *Guidelines *Immunotherapy *Metastatic *Systemic therapy *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

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 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

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.

Adjuvants Immunologic/administration & dosage Administration Intravesical BCG Vaccine/*adverse effects Chondroitin Sulfates/*administration & dosage Cystitis/chemically induced/pathology/*prevention & control Humans Hyaluronic Acid/*administration & dosage Immunotherapy/*adverse effects Randomized Controlled Trials as Topic Urinary Bladder Neoplasms/pathology/*therapy

Bladder cancer Pd-1 Pd-l1 atezolizumab avelumab biomarkers durvalumab immunotherapy nivolumab pembrolizumab Urogen licenses/patents: University of Colorado research support: Medivation/Astellas stockholder in: Aurora Oncology PrecisionProfile other: IOS Press (editorial responsibilities compensated).The other authors report no conflicts of interest.

Administration Intravesical Aged Aged 80 and over BCG Vaccine/*therapeutic use Biopsy Needle Disease-Free Survival Female Humans Immunohistochemistry Immunotherapy/*methods In Situ Hybridization Fluorescence Male Middle Aged Neoplasm Recurrence Local/mortality/*pathology Predictive Value of Tests Prognosis Risk Assessment Survival Analysis Treatment Outcome Urinary Bladder Neoplasms/mortality/pathology/*therapy Bcg Bladder cancer Immunotherapy Personalized therapy Response prediction

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

Administration Intravesical Antineoplastic Agents/*administration & dosage/adverse effects Asymptomatic Diseases BCG Vaccine/*administration & dosage/adverse effects Bacteriuria/*complications/diagnosis Humans Immunotherapy/adverse effects/*methods Neoplasm Invasiveness Risk Assessment Treatment Outcome Urinary Bladder Neoplasms/complications/*drug therapy/immunology/pathology Bacillus Calmette-Guerin Bacteriuria Bladder cancer Intravesical instillation

Adjuvants Immunologic/administration & dosage Administration Intravesical Antineoplastic Agents/therapeutic use BCG Vaccine/*administration & dosage Bayes Theorem Disease Progression Humans Immunotherapy/*methods Incidence Neoplasm Recurrence Local/drug therapy Randomized Controlled Trials as Topic Urinary Bladder Neoplasms/*drug therapy Intravesical bacillus Calmette–Guerin efficacy maintenance non-muscle-invasive bladder cancer side effects

Adult Aged Aged 80 and over Antibodies Monoclonal/therapeutic use Antibodies Monoclonal Humanized/therapeutic use B7-H1 Antigen/*antagonists & inhibitors/genetics CTLA-4 Antigen/*antagonists & inhibitors/genetics Clinical Trials as Topic Female Genes cdc/drug effects Humans Ipilimumab Male Middle Aged Neoplasm Metastasis/*drug therapy/genetics/pathology Nivolumab Urinary Bladder Neoplasms/*drug therapy/genetics/pathology Bladder cancer immunotherapy Checkpoint inhibitor Pembrolizumab

Adjuvants Immunologic/*therapeutic use BCG Vaccine/*therapeutic use Humans Mycobacterium bovis Urinary Bladder Neoplasms/*drug therapy/pathology BCG vaccine immunotherapy urinary bladder neoplasms