For decades, cell lines have formed the foundation of in vitro cancer research due to their predictable biology, ease of use, and the ability to standardize data amongst the research community. While the work performed with these cells has led to major advances in prostate cancer (PC) treatment, there are numerous limitations in cell line research that present major barriers to new therapy development. Specifically, cell lines can express key variations in cell biology and the tumor models developed with these cells often fail to represent patient heterogeneity as well as the multi-cellular environment within tumors. In order to address these limitations, patient-derived cancer organoid (PDCO) models have become increasingly utilized for cancer research.