Clinicopathological features and treatment outcomes of urothelial carcinoma variant histologies and non-urothelial bladder cancers

Most bladder cancers are pure urothelial carcinomas, but a small portion, approximately 5-10%, have variant histology or are non-urothelial in nature. This research sought to examine the features of and treatment strategies for different types of urothelial carcinoma with variant histologies and non-urothelial bladder cancer. The study cohort comprised individuals with non-urothelial and variant urothelial bladder cancers treated at two medical centres in Ankara, Turkey, between 2005 and 2024. A total of 104 individuals were reviewed, with 88 having urothelial cancer with variant histology and 16 having non-urothelial cancer. Non-urothelial cancers included neuroendocrine, undifferentiated, adenocarcinoma, squamous, sarcoma, and carcinosarcoma, with a median overall survival (OS) of 8 months. The most frequent urothelial carcinoma variants were squamous (43 cases), plasmacytoid (9 cases), and sarcomatoid (6 cases). Individuals with operable variants of urothelial malignancies had a median disease-free survival (DFS) of 16.5 months, while individuals with inoperable/metastatic variants experienced a median progression-free survival (PFS) of 8.9 months. The median OS in the operable cohort was 18.5 months, compared to 10.8 months in the inoperable/metastatic group. The present study reveals that variant urothelial and non-urothelial bladder cancers are aggressive in nature and have poor prognosis. Given the significant heterogeneity observed in OS, DFS, and PFS among these rare and diverse tumor subtypes, large-scale multicenter investigations are required to establish a consensus on patient handling and treatment.