Toward Personalized Treatment of Urogenital Cancers: The Role of Patient-Derived Organoids

Urogenital cancers, including prostate, kidney, and bladder cancer, remain a significant clinical challenge due to their high incidence, molecular heterogeneity, and frequent resistance to standard therapies. Despite progress in genomic profiling and precision oncology, the translation of molecular data into effective therapeutic decisions remains limited by the lack of functional models capable of capturing tumor complexity. Patient-derived organoids (PDOs) have emerged as transformative tools in this context, offering the unique advantage of preserving the genetic, phenotypic, and functional features of individual tumors ex vivo. Beyond their well-established applications in drug screening and resistance studies, PDOs contribute to personalized treatment strategies by enabling functional molecular stratification, modeling tumor–microenvironment interactions, and predicting the efficacy of targeted and immunotherapeutic approaches. When integrated with liquid biopsy analyses, PDOs also allow real-time tracking of clonal evolution and can be repeatedly generated during the disease course, providing dynamic insights that guide longitudinal treatment decisions. As organoid biobanking and multi-omic integration advance, PDOs are poised to evolve into clinically actionable avatars that complement genomic profiling and help tailor therapeutic strategies for patients with urogenital cancers. Nevertheless, the clinical integration of PDOs still faces important barriers, including variability in culture protocols, incomplete representation of the native tumor microenvironment, and the time required for organoid establishment. Moreover, the predictive value of PDO-based drug screening—although promising—needs rigorous prospective validation in large patient cohorts. This review highlights the pivotal role of PDOs in bridging the gap between laboratory research and clinical oncology, emphasizing their application in guiding personalized therapeutic strategies. As organoid biobanking and genomic profiling expand, the integration of PDOs into precision oncology pipelines holds promise for reshaping the clinical management of urogenital malignancies and advancing toward truly individualized cancer treatment.