Abstract

BackgroundWe investigated whether Imunoscore performed on localized or locally advanced urothelial carcinoma (UC) tumor samples could predict response to neoadjuvant chemotherapy and survival outcome. MethodsThis retrospective ongoing study evaluated the Immunoscore in 150 patients with UC (140 UC of the bladder, 10 UC of the upper tract) from 6 centers (Greece and France). All patients underwent neo-adjuvant chemotherapy. Pre-treatment tumor samples (trans-urethral resection or upper tract biopsy) were immunostained for CD3+ and CD8+ T cells and quantified by digital pathology to determine the Immunoscore. The consensus Immunoscore was applied to tumors with invasive margin and an Immunoscore adapted to samples quantified when no invasion was identified on the specimen. Results were correlated with response to neoadjuvant treatment and time to recurrence (TTR). ResultsImmunoscore Low, Intermediate and High were respectively observed in 40, 43 and 17% of the cohort. Densities of CD3 and CD8 in the center and invasive margin were not significantly different according to clinical parameters such as T-stage, N-stage, age, gender, tumor differentiation (with or without variant), and localization (upper tract versus bladder). Immunoscore was positively and significantly correlated with TTR. High, intermediate and low Immunoscore patients had a median TTR of 83, 34 and 27 months, respectively (P<0,05). In multivariate analysis, Immunoscore remains a significant independent parameter at presentation associated with TTR (High vs Low: P<0.05). Immunoscore was positively and significantly correlated with pathologic complete response (pCR) (P<0.001). Low Immunoscore was observed in 69% of patients with no pCR, and in only 20% of patients with pCR. In contrast, high Immunoscore was observed in only 7% of patients with no pCR, whereas 40% of these patients had a pCR. ConclusionsThe results of this ongoing study show a significant prognostic and potentially predictive role of Immunoscore in UC patients with important therapeutic implications. These preliminary results will be completed as samples are being analyzed before ESMO 2019 annual meeting. Legal entity responsible for the studyThe authors. FundingFONCER. DisclosureC. Thibault: Honoraria (self), Travel / Accommodation / Expenses: Astellas Pharma; Honoraria (self): Ipsen; Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen-Cilag; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Sanofi Pasteur; Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca/Medimmune; Travel / Accommodation / Expenses: Astellas; Travel / Accommodation / Expenses: Roche/Genentech. F. Hermitte: Shareholder / Stockholder / Stock options, Full / Part-time employment: HalioDx. A. Bamias: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Pfizer; Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Advisory / Consultancy, Research grant / Funding (self): Ipsen; Research grant / Funding (self): Lilly; Research grant / Funding (self): Astellas. J. Galon: Advisory / Consultancy, Research grant / Funding (institution), Shareholder / Stockholder / Stock options: HalioDx; Honoraria (self): AstraZeneca; Honoraria (self): Novartis; Honoraria (self): Merck; Honoraria (self): MSD; Honoraria (self): BMS; Honoraria (self): Sanofi; Honoraria (self): Gilead; Advisory / Consultancy, Research grant / Funding (institution): Io Biotech; Advisory / Consultancy: Illumina; Advisory / Consultancy: Northwest Biotherapeutics; Advisory / Consultancy: Actelion; Advisory / Consultancy: Amgen; Research grant / Funding (institution): Perkin Elmer; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Imcheck; Licensing / Royalties: INSERM. All other authors have declared no conflicts of interest.

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