A Feasibility Study of Co-Established Patient-Derived Subcutaneous Xenograft and Organotypic Slice Cultures in Hormone-Naive Primary Prostate Cancer Preclinical Modeling: A Single-Institution Experience

Background: Preclinical models that preserve the tumor microenvironment are critically needed in prostate cancer (PCa) research. Patient-derived xenografts (PDXs) and patient-derived Organotypic Slice Cultures (PD-OSCs) have emerged as promising in vivo and ex vivo platforms to address this gap and better mimic human tumor biology. Methods: Subcutaneous PDX models and PD-OSCs were established in parallel from fresh, primary hormone-naïve PCa patient tissues. PDX models were generated by engrafting tumor fragments into immunodeficient mice, while PD-OSCs were maintained as short-term ex vivo cultures for functional analysis. Results: A cohort of 64 PDXs and 45 PD-OSCs was generated. While first-generation PDX engraftment was successful, subsequent passaging and model expansion were extremely poor. In contrast, PD-OSCs were reliably established, maintained tissue viability, and proved to be a robust platform for functional testing, including gene expression analysis and drug sensitivity screening. Conclusions: Our findings establish both first-generation PDXs and PD-OSCs as valuable “avatar” models for translational research. However, PD-OSCs represent a more efficient and rapid platform for studying primary hormone-naïve PCa biology and evaluating treatment responses, holding significant promise as a predictive tool to guide personalized medicine.