Building Fit-for-Purpose, Multi-Lineage Immune–Organoid Models for Urologic Cancers: A Critical Narrative Review of Prostate, Urothelial and Renal Cell Carcinoma Models

Immune–organoid co-culture has been proposed as a bridge between reductionist assays and clinical immuno-oncology, but the urologic evidence remains substantially thinner than this description suggests. This critical narrative review evaluates peer-reviewed work in prostate cancer, urothelial carcinoma and renal cell carcinoma from January 2014 through to 31 July 2026, separating patient-derived immune-preserving models from reconstituted cytotoxicity assays and adjacent engineering studies. Native air–liquid interface cultures have retained endogenous lymphoid, myeloid and stromal compartments in renal cell carcinoma for short-term checkpoint-inhibitor experiments. Reconstituted bladder and kidney organoids have supported mechanistic testing of chimeric antigen receptor T cells, and a bladder study has examined treatment-induced Jurkat-cell migration. These studies establish technical feasibility, but most use small cohorts, short endpoints and incomplete immune composition, and none has prospectively shown that a multi-lineage urologic organoid assay improves treatment selection. Published prostate systems remain largely epithelial or stromal, leaving a conspicuous immune-modelling gap. We therefore argue against equating greater cellular complexity with greater validity. The appropriate model is the least complex system that preserves the mechanism, spatial constraint and temporal window required by the question. A tiered framework is proposed that progresses from analytical quality control, through defined effector and suppressor modules, to perfused or spatially organised cultures only when these features are necessary. Minimum reporting standards, disease-specific immune modules, clinically meaningful endpoints and a four-stage validation ladder are specified. Multi-lineage systems can clarify resistance mechanisms and screen combinations, but predictive or clinical claims require blinded patient concordance and prospective utility studies rather than architectural sophistication alone.