Promise or predicament? Real-world analysis of molecular targets and therapy approaches in uro-oncology.

Abstract

e17022 Background: Despite ongoing research and evolving therapeutic landscapes, advanced urological malignancies such as prostate cancer (PC), bladder/urothelial cancer (BC), renal cell carcinoma (RCC), and penile cancer (PeC) remain associated with an unfavorable prognosis. While molecularly targeted therapies in PC are already clinically established, their use in other urological entities remains limited. The aim of this study was to analyze the real-world implementation of molecular diagnostics and its therapeutic consequences in a single-center tertiary setting. Methods: In a retrospective database analysis, all patients presenting at our university-based interdisciplinary tumor board (ITB) between 2018 and 2024 were included. Cases with a recommendation for molecular diagnostics were identified and categorized according to tumor entity. Molecular analyses were performed using disease-specific or pan-oncological next-generation sequencing (NGS) panels. Treatment recommendations were evaluated by the Molecular Tumor Board (MTB). Molecular data (including mutations, therapy recommendations, level of evidence, and administered molecular therapies), were analyzed. Results: Out of a total of 11,562 cases discussed in the ITB, molecular diagnostics followed by presentation at the MTB were recommended in 332 (2.9%) cases. Molecular analyses were actually performed in 113 (29.4%, overall cohort: 1.5%) patients, including 64 PC, 24 BC, 22 RCC, and three PeC patients, as well as 66 cases with isolated BRCA testing. The most frequent genetic alterations were PTEN in PC, HER2 and FGFR in BC, VHL in RCC, and EGFR in PeC. BRCA1/2 mutations were detected in 13.6%. Molecularly targeted therapies were initiated in 14 patients including PARP inhibition. Conclusions: Molecular diagnostics is gaining increasing importance in urological oncology; however, in routine clinical practice it rarely translates into therapeutic consequences. BRCA testing and PARP inhibition were the most common treatment. These findings highlight the need for structured molecular testing, prospective data collection, and further development of evidence-based treatment options to better exploit the potential of personalized therapies in uro-oncology.