First-line systemic treatments for bladder cancer are based on a combination of cytotoxic and immunotherapy, sequentially or concomitantly. Immune checkpoint inhibition (ICPI) is a powerful treatment for patients with metastatic urothelial carcinoma (UC). Since 2017, pembrolizumab (anti-PD1) can be offered as a second-line treatment after failure of platinum agents. In patients responding to platinum salts in first-line treatment, it is possible to maintain efficacy with maintenance treatment with another ICPI, avelumab (anti-PDL1). The phase III JAVELIN BLADDER 100 study compared avelumab to supportive care alone after successful platinum-based chemotherapy. At 30 months, 19.3% of patients were still in response compared to only 6.3% in the supportive care arm. However, biomarker analysis on tumor tissue did not show a robust signature on an individual scale. Recently, two phase 3 trials in first-line were presented at the ESMO 2023 congress. The first, in patients who could receive cisplatin-based chemotherapy, found a benefit on overall survival of adding Nivolumab in combination and then maintaining it for two years. The second proposed combined Enfortumab Vedotin and Pembrolizumab versus standard chemotherapy, with an overall survival for the study arm of more than 31 months. These trials confirm the essential role of immunotherapy in urothelial carcinomas. This progress is tempered by toxicity, cost and the lack of data on patient selection and treatment sequence. Although "prognostic" biomarkers have been identified, they cannot guide the choice of therapy, but only predict the expected outcomes, regardless of the treatment; biomarkers capable of predicting clinical benefit ("predictive") are urgently needed. It is therefore essential to identify a predictive signature at the individual level. The study authors have validated an in vitro model of heterotypic spheroids (SPHERTEST) composed of commercial urothelial carcinoma tumor cells and PBMCs from healthy donors. The aim of the study is to validate this model with PBMCs from UC patients to evaluate the effects of immunotherapy on the immune response and on tumor cell survival in vitro.

The study hypothesis is that the outcome of the pre-therapeutic test based on a heterotypic spheroid model with PBMC from patients with advanced or metastatic urothelial carcinoma (SPHERTEST) is related to the response to checkpoint inhibitor (CI) treatment.

Inclusion Criteria:

• Patient with histologically proven urothelial carcinoma, in a locally advanced or metastatic situation with indication for immunotherapy.
• The patient must have given their free and informed consent and signed the consent form
• The patient must be a member or beneficiary of a health insurance plan

Exclusion Criteria:

• The subject is participating in a category 1 or drug monotherapy interventional study, or is in a period of exclusion determined by a previous study
• It is impossible to give the subject informed information
• The patient is under safeguard of justice or state guardianship
• History of treatment with anti-PD1 or anti-PDL1 or anti-CTLA4 within the year.
• Pregnant, parturient or breastfeeding patient.

The study population consists of patients with advanced or metastatic urothelial carcinoma with an indication for treatment with an immune checkpoint inhibitor treated in the onco-urology departments of the Nîmes University Hospitals, the Antoine Lacassagne Center, the IUCT Toulouse and the Montpellier Regional Cancer Institute.