Abstract Background Prognostic factors for survival in metastatic urothelial carcinoma (mUC) have been established in patients (pts) treated with chemotherapy. However, their role has not been clearly defined in the era of immune-checkpoint inhibitors (ICIs). We have previously reported the Vall d’Hebron immuno-oncology prognostic index (VIO score) for refractory pts treated in phase I clinical trials with ICIs (Hierro C, et al ESMO 2018). In this retrospective study, we assessed VIO in pts with mUC treated with ICIs. Methods Pts with mUC enrolled from May 2015 to May 2018 in clinical trials at the Vall d’Hebron University Hospital were analysed. VIO score includes: albumin < 3.5 g/dl; LDH> upper limit of normal; neutrophil/leukocytes minus neutrophils ratio (dNLR) > 3; more than 2 sites of metastasis; and presence of liver metastasis. The following VIO clusters were defined: good prognosis (0-1), intermediate prognosis (2) and poor prognosis (³3 variables). Median overall survival (OS) was calculated using Kaplan-Meier method, long rank test was used for statistical comparison. All analyses were performed using SPSS v25; IBM Inc. Results Overall, 86 mUC pts received therapy with ICIs and 72 pts with complete annotation for VIO index were included in our analysis. Median age was 67.4 years, 62 (86.1%) pts were male, 66 pts (91.7%) had ECOG PS 0-1, 17 pts (23.6%) had liver metastasis and 8 pts (72%) had >2 sites of metastasis. Forty-eight pts (66.6%) were treated with ICIs as monotherapy and 24 pts (33.3%) in combination regimens. Follow-up was 13.2 moths (m) (95% CI; 10.5-15.9) and median OS was 11.3 m (95% CI; 7.1-15.4) in the evaluable population. Estimated mOS in good prognosis (62.5% of all pts), intermediate prognosis (23.6%) and poor prognosis (13.9%) were 19.3 m (95% CI; 5.1-33.6), 8.2 m (95% CI; 3.3-13.1) and 2.9 m (95% CI;0.1-7.7), respectively (p < 0.001). 3-m OS rates were 95.6%, 82.4% and 50% for good, intermediate and poor prognosis, respectively (p = 0.001). Conclusions VIO score is a powerful tool for predicting outcome in mUC pts treated with ICI and objectively estimating their life expectative at 3 m, which can help prioritize alternative therapies in clinical trials. Legal entity responsible for the study Vall d’Hebron Institute of Oncology, Vall d’ Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain. Funding Has not received any funding. Disclosure R. Morales Barrera: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Sanofi; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Asofarma; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Astellas; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Johnson & Johnson; Honoraria (institution), Travel / Accommodation / Expenses: Bayer; Honoraria (institution), Travel / Accommodation / Expenses: Clovis Oncology; Honoraria (institution), Travel / Accommodation / Expenses: Lilly; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche/Genentech; Research grant / Funding (institution): AB Science; Research grant / Funding (institution): Aragon Pharmaceuticals; Research grant / Funding (institution): Arog Pharmaceuticals; Research grant / Funding (institution): INC; Research grant / Funding (institution): Aveo Pharmaceuticals INC; Research grant / Funding (institution): Blueprint Medicines Corporation; Research grant / Funding (institution): BN Immunotherapeutics INC; Research grant / Funding (institution): Boehringer Ingelheim España, S.A.; Research grant / Funding (institution): Cougar Biotechnology INC; Research grant / Funding (institution): Deciphera Pharmaceuticals LLC; Research grant / Funding (institution): Exelixis INC; Research grant / Funding (institution): Glaxosmithkline; Research grant / Funding (institution): Incyte Corporation; Research grant / Funding (institution): Karyopharm Therapeutics INC; Research grant / Funding (institution): Laboratoires Leurquin Mediolanum SAS; Research grant / Funding (institution): Medimmune; Research grant / Funding (institution): Millennium Pharmaceuticals; Research grant / Funding (institution): Nanobiotix SA; Research grant / Funding (institution): Novartis Farmacéutica, S.A; Research grant / Funding (institution): Pfizer, S.L.U; Research grant / Funding (institution): Puma Biotechnology; Research grant / Funding (institution): SFJ Pharma LTD; Research grant / Funding (institution): Teva Pharma S.L.U. M. Gonzalez: Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Astellas; Travel / Accommodation / Expenses: Bayer; Travel / Accommodation / Expenses: Novartis. C. Suárez: Research grant / Funding (institution): AB Science; Research grant / Funding (institution): Aragon Pharmaceuticals; Research grant / Funding (institution): Arog Pharmaceuticals; Advisory / Consultancy, Research grant / Funding (institution): Astellas Pharma; Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca AB; Research grant / Funding (institution): Aveo Pharmaceuticals INC; Research grant / Funding (institution): Bayer AG; Research grant / Funding (institution): Blueprint Medicines Corporation; Research grant / Funding (institution): BN Immunotherapeutics INC; Research grant / Funding (institution): Boehringer Ingelheim España, S.A.,; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol-Myers Squibb International Corporation (BMS),; Research grant / Funding (institution): Clovis Oncology; Research grant / Funding (institution): Cougar Biotechnology INC; Research grant / Funding (institution): Deciphera Pharmaceuticals LLC; Research grant / Funding (institution): Exelixis INC; Research grant / Funding (institution), Travel / Accommodation / Expenses: Hoffmann-La Roche LTD; Research grant / Funding (institution): Genentech INC; Research grant / Funding (institution): Genentech INC; Research grant / Funding (institution): GlaxoSmithKline, SA; Research grant / Funding (institution): Incyte Corporation; Research grant / Funding (institution): Janssen-Cilag International NV; Research grant / Funding (institution): Karyopharm Therapeutics INC; Research grant / Funding (institution): Lilly, S.A; Research grant / Funding (institution): Millennium Pharmaceuticals, INC; Research grant / Funding (institution): Nanobiotix SA; Research grant / Funding (institution): Novartis Farmacéutica, S.A; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Research grant / Funding (institution): Puma Biotechnology; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Sanofi-Aventis, S.A; Research grant / Funding (institution): SFJ Pharma LTD. II; Research grant / Funding (institution): Teva Pharma S.L.U.; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy: Eusa; Advisory / Consultancy: Novartis. C. Fernandez: Travel / Accommodation / Expenses: AstraZeneca. C. Hierro: Research grant / Funding (self): Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Travel / Accommodation / Expenses: Ignyta. E. Serra: Travel / Accommodation / Expenses: Clovis Oncology; Travel / Accommodation / Expenses: Bayer. J. Mateo: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy: Roche; Advisory / Consultancy: Amgen; Speaker Bureau / Expert testimony: Sanofi. J. Martín Liberal: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pierre Fabre; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Ipsen. A. Quintana: Honoraria (self): Fundación Respira; Travel / Accommodation / Expenses: MSD. R. Dienstmann: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Symphogen; Speaker Bureau / Expert testimony: Ipsen; Speaker Bureau / Expert testimony: Amgen; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: Servier; Research grant / Funding (self): Merck. C. Serrano: Advisory / Consultancy, Research grant / Funding (institution): Deciphera; Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy: Blueprint; Travel / Accommodation / Expenses: PharmaMar; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: Lilly. E. Garralda: Advisory / Consultancy, Research grant / Funding (institution): Roche/Genentech; Advisory / Consultancy: Ellipses Pharma; Advisory / Consultancy: Neomed Therapeutics; Advisory / Consult