401 Background: Considerable numbers of patients (pts) with metastatic urothelial carcinoma (mUC) (approximately 25-47%) develop bone metastases (BoM). Their impact on the efficacy of immunotherapy (IO) is not yet sufficiently investigated. We developed a national collaboration on this issue, with the aim to assess the effect of BoM on survival outcomes of immunotherapy-treated pts in a large retrospective cohort. Methods: Data on pts diagnosed with mUC and treated between 07/14 and 08/20 with single-agent immunotherapy (IO) after failure of at least 1 previous line of chemotherapy (CT) for advanced disease, or (neo-)adjuvant CT within 12 months were retrospectively collected across 14 centers. PFS and OS were analyzed using the Kaplan-Meier method. Cox regression analysis was performed evaluating potential prognostic factors for OS and PFS. Each factor was evaluated in univariable (UV) and multivariable (MVA) analysis. Results: A total of 208 evaluable pts treated with single-agent immunotherapy (anti PD-1 n=42; anti PD-L1 n=166) were identified, including 122 without BoM (59% BoM-) and 86 (41%) BoM+. 13% of pts had progressed within 12 months after (neo-)adjuvant CT and 79% after a previous line of platinum-based CT for advanced disease (cisplatin 42.8%; carboplatin 36.5%). The presence of BoM negatively affected performance status (PS) of patients at baseline (ECOG PS 0/1/2 in 58% / 37% / 5% in BoM- vs 38% / 52% / 9% in BoM+; p=0.017). Other baseline characteristics were comparable. BoM+ showed shorter PFS (median 2.0 vs 2.6 months, HR 1.76 [95%CI, 1.31-2.37], p<0.001) and OS (median 3.9 vs 7.8 months, HR 1.59 [95%CI, 1.15-2.20], p=0.005) than BoM-. Probability of being alive was 62% vs 40% after 6 months, 38% vs 23% after 1 year and 24% vs 13% after 2 years, in BoM- and BoM+ respectively. Within each Bellmunt score, PFS and OS of BoM+ pts were shorter compared to BoM-. Both BoM and higher Bellmunt risk score were significantly associated with shorter PFS and OS in UV and MV analyses (Table). Conclusions: Patients with mUC treated with single-agent immunotherapy for BoM+ advanced disease have a dismal prognosis compared with BoM-. Further research is needed to understand the mechanism behind these clinical outcomes. [Table: see text]