Emre AKAR, Halil Fırat BAYTEKİN, Öykü Dila GEMCİ, Selçuk ŞAHİN, Serdar ALTINAY, Kanay YARARBAŞ, Deniz TURAL
Journal of Urological Surgery - 2026;13(3):172-177
Objective: Urothelial carcinoma is an aggressive malignancy with limited therapeutic options in the metastatic setting. Neurotrophic receptor tyrosine kinase (NTRK) gene fusions are actionable alterations in several solid tumors; however, their prevalence and clinical relevance in bladder cancer remain unclear. Materials and Methods: A retrospective analysis was performed on cystectomy specimens from 60 patients with metastatic urothelial carcinoma who were treated between 2009 and 2021 at a single tertiary center. Tropomyosin receptor kinase (TRK) protein expression was evaluated by immunohistochemistry using a pan-TRK antibody. Positive cases were further analyzed for NTRK1/2/3 fusions using a real-time polymerase chain reaction assay detecting 109 known variants. Clinicopathological parameters and survival outcomes were reviewed. Results: The cohort included 55 males (91.7%) and 5 females (8.3%), with a median age of 62 years. At cystectomy, all tumors were high-grade, with pathological stages ranging from pT1 to pT4a. Median overall survival was 49.5 months, and median survival after progression to metastatic disease was 19.5 months. Pan-TRK positivity was observed in 2 of 60 cases (3.3%). Molecular analyses of these samples revealed no NTRK fusions, indicating isolated TRK protein overexpression without gene rearrangements. Conclusion: TRK expression was rare, and NTRK fusions were absent in this cohort with metastatic urothelial carcinoma. These results suggest that TRK-targeted therapies are unlikely to benefit unselected bladder cancer populations. Nonetheless, systematic molecular profiling remains essential for identifying patients with rare targetable alterations, while TRK signaling does not appear to represent a major oncogenic driver in urothelial carcinoma.
