Establishment of a clear cell renal cell carcinoma organoid cohort integrated into the UroCCR clinical database: A feasibility study

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the sixth most common cancer in France. While early-stage survival rates are high in early stages, they decrease significantly in metastatic stages, due to tumor heterogeneity and treatment resistance. The development of reliable preclinical models is essential to improve targeted therapies. This study aimed to evaluate the feasibility of establishing patient-derived ccRCC organoids linked to the UroCCR clinical database. METHODOLOGY: Tumor samples from total or partial nephrectomies performed at Caen University Hospital between November 2023 and March 2024 were processed for organoid culture. Seven culture conditions were tested, including different extracellular matrices (Matrigel, collagen I) and growth factor-enriched media. RESULTS: Organoids were established in 12 of 18 cases (66.7%). Among these, five cultures were successfully expanded and characterized histologically (42%). Organoids were maintained in culture for a median of 52 days and underwent a mean of two passages. Histological analyses showed that organoids retained several morphological features consistent with the original tumors, although variability in CA-IX and CK7 expression was observed. SIGNIFICANCE: This feasibility study demonstrates that ccRCC organoid generation from surgical specimens is achievable but remains limited by variable establishment rates and culture duration. Further optimization and integration of microenvironmental components will be necessary to enhance the translational relevance of this model.