After completion of cystectomy, we could document normal serum marker levels from 288 cases, of whom 27 patients (9%) developed tumor marker relapse later during follow up. This subset showed significantly more clinical recurrences (89% in elevated vs. 12% in stable group, RR ¼ 7.41), and death (26% vs. 7%, RR ¼ 3.4). Median time from tumor marker relapse to clinical recurrence was 46 days (IQR 0-179), and median time to mortality was 308 days (IQR 119-574) days. Details of tumor markers course in the 24 patients with marker relapse followed by clinical recurrence is shown in Figure 2. Further Survival analysis using landmark time-point with log rank showed there is a significant difference in cancer- specific survival between the groups (median 284 vs 547 days; p ¼ 0.01) (Figure 2). Conclusions: To our knowledge, this is the first study of its kind. Patients with persistently elevated markers following NAC have a very poor prognosis following cystectomy, which may help in identifying chemotherapy-resistant tumors. Also, patients with marker relapse following cystectomy are at significant increased risk of recurrence and mortality. A larger, controlled study with longer follow up is needed to determine the role of these markers in predicting survival. Improving immune-gene therapy for bladder cancer Colin Dinney, Devine Plote, Deb Sundi, Michael Metcalfe, Sharada Mokkapati, Bogdan Czerniak, Ashish Kamat, Neema Navai, Kimberly Schluns, David McConkey. The University of Texas MD Anderson Cancer Center, Houston, TX, USA;, Greenberg Bladder Cancer Institute, Johns Hopkins University, Baltimore, MD, USA Introduction: Intravesical immunotherapy with Bacillus Calmette-Guerin (BCG) remains the frontline therapy for patients with high-grade (HG) non- muscle invasive bladder cancer (NMIBC). Although BCG produces initial clinical activity in a majority of patients, recurrence and progression are common as patients develop BCG-Unresponsive disease. Several agents have been tested in the second-line setting, but to date, few have provided durable responses. We developed adenoviral interferon-alpha (Ad-IFNα) for intravesical delivery using a novel adjuvant (Syn-3) to enhance viral transduction of the urothelium. Materials and methods: We completed a Phase I clinical trial in the BCG- Unresponsive population and demonstrated that Ad-IFNα/Syn3 produced high, sustained levels of urine IFNα and clinical responses in approximately 35% of patients and subsequently led a Society of Urologic Oncology Clinical Trials Consortium (SUO-CTC) supported Phase II clinical trial of intravesical Ad-IFNα in this same patient population with durable responses again reported in 35% of patients and a Phase III trial with the SUO-CTC is ongoing. Preclinical studies show that IFNα activates the innate and adaptive arms of the host immune system by promoting antigen processing and presentation, the maturation of dendritic cells and their migration to draining lymph nodes, and the recruitment and activation of NK and tumor-specificT cells. In addition, IFNα induces PD-L1 expression on tumor cells, which could attenuate the beneficial effects of IFNα on T cell activation. Conclusions: We hypothesize that Ad-IFNα, with its ability to induce prolonged IFNα production, will enhance recruitment and activation of tumor- specific cytotoxic T lymphocytes leading to improved, meaningful clinical responses as a monotherapy and as part of a combination therapy with PD-L1 inhibitors, will produce even more durable CRs that overcome therapy resistance. Specific risk patterns for bladder cancer taxonomy-based subphenotypes Sara Domínguez, Marta Rava, Nanour Sirab, Adonina Tardón, Alfredo Carrato, Consol Serra, Reina García-Closas, Nathaniel Rothman, Debra Silverman, Manolis Kogevinas, Yves Allory, Francisco X. Real, Núria Malats. Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), Madrid, and CIBERONC, Spain;, Pathology Department, Henri Mondor Hospital, IMRB, Créteil, France;, Department of Preventive Medicine, Universidad de Oviedo, and CIBERESP, Spain;, Servicio de Oncología, Hospital Universitario Ramon y Cajal, Madrid, Servicio de Oncología, Hospital Universitario de Elche, and CIBERONC, Spain;, Center for Research in Occupational Health (CiSAL), Universitat Pompeu Fabra, Department of Occupational Health, Parc de Salut MAR, Barcelona, and CIBERESP, Spain;, Hospital Universitario de Canarias, La Laguna, Spain;, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, Bethesda, Maryland, USA;, Centre for Research in Environmental Epidemiology (CREAL), Parc de Salut Mar, Barcelona, and CIBERESP, Madrid, Spain;, Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, and CIBERONC, Spain Background: Urothelial bladder cancer (UBC) is a complex disease with diverse genetic and environmental factors participating and interacting in its development. There is evidence that UBC is heterogeneous at both pathological and molecular levels. A molecular taxonomy has been proposed with at least two UBC subgroups: basal-squamous (BASQ) and luminal-like. BASQ tumors have been defined by consensus as being KRT14-high and KRT5/6-high and GATA3-low and FOXA1-low protein expression. This study aims to assess the association of non-genetic risk factors with UBC molecular subphenotypes. Methods: Subjects, epidemiological and clinicopathological data, and samples from the Spanish Bladder Cancer/EPICURO Study were used. FFPE blocks were used to build tissue microarrays (NMIBC, n ¼ 929; MIBC, n ¼ 271). Immunohistochemical expression of KRT5/6, FOXA1 and GATA3 was assessed to define BC subphenotypes by means of unsupervised hierarchical cluster analysis. Multiple imputation was applied to complete cluster allocation for a total series of 904 cases. Associations between UBC subphenotypes and environmental, life-style factors, as well as clinical parameters were evaluated with multinomial logistic regression models, adjusted for age, gender, and region, considering 1274 controls as a reference group. Results: Three UBC clusters were identified: BASQ (N ¼ 65, 7%), luminal-like (high GATA3-FOXA1, low KRT14-KRT5/6, N ¼ 595, 66%) and mixed (N ¼ 247, 27%). BASQ-like tumors were mostly MIBC and non-papillary. They were less strongly associated with tobacco smoking and risk-occupational exposures and more strongly associated with bladder infections. Luminal-like tumors were inversely associated with NSAIDs consumption and high levels of plasma vitamin D. Mixed-like tumors were inversely associated with asthma and BPH. Conclusions: This study provides suggestive evidence that UBC subphenotypes display distinct etiological associations with environmental/life-style factors. This represents the largest and more comprehensive study on UBC subphenotyping conducted at present. Our findings need to be replicated in independent studies. Myeloid derived suppressor cells (MDSC) correlate with inflammatory biomarkers in metastatic urothelial carcinoma (mUC) Petros Grivas, C. Marcela Diaz-Montero, Patricia A. Rayman, Paul Elson, Samuel Haywood, Jin Sub Kim, Paul G Pavicic, James Finke, Brian I. Rini, Andrew J. Stephenson, Marcelo Lamenza, Priscilla Dann, Kim Schach, Sarah Devonshire, Jennifer S. Ko, Amr Farouk Fergany, Marc S. Ernstoff, Christopher J. Hoimes, Jorge A. Garcia, Moshe Chaim Ornstein. Department of Hematology & Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA Objectives: MDSC are potent immunosuppressive cells with prognostic implications in solid tumors. We previously reported significant correlations between MDSC and clinicopathologic features in localized UC. We hypothesized that different MDSC populations may correlate with inflammatory biomarkers and clinicopathologic features in mUC. Materials and methods: Peripheral blood samples were collected from 59 mUC pts. MDSCs were measured in fresh unfractionated whole blood (WB) and in peripheral blood mononuclear cells (PBMC). MDSCs were identified by flow cytometry in WB and defined as LinloCD33þ/HLADR- [(T)otal MDSC]. MDSC subsets were defined as (G)ranulocytic (CD15þCD14-), (M)onocytic (CD15-CD14þ), (I)mmature (CD15-CD14-), or CD11bþ . MDSC populations were presented as % of live nucleated IBCN Abstracts / Urologic Oncology: Seminars and Original Investigations 35 (2017) 608–621 611