Histologic subtypes and divergent differentiations of urothelial carcinoma: Prognostic implications and clinical...

Bladder cancer is a major global health concern, and urothelial carcinoma (UC) often presents with diverse histologic subtypes and differentiations associated with aggressive behavior and poorer survival with no standardized treatment recommendations. This study aimed to compare clinicopathologic characteristics and survival outcomes between patients with histologic/divergent UC subtypes and those with pure UC at initial presentation.

We retrospectively analyzed 506 patients with de novo UC identified at initial transurethral resection of the bladder (TUR-BT) between 2015 and 2023. Demographic and clinical characteristics, pathologic features, treatment strategies, and survival outcomes were compiled and compared between groups. Treatment strategies, including radical cystectomy and neoadjuvant chemotherapy, were also evaluated to examine how histologic subtypes influenced clinical decision-making.

Median follow-up period was 71 months (95 % CI, 68.0-74.0). Patients with histologic subtypes and divergent differentiations demonstrated significantly more aggressive tumor features at diagnosis, including higher rates of muscle invasion (46.1 % vs. 28.8 %, p < 0.001) and lymphovascular invasion (LVI) (38 % vs. 13.5 %, p < 0.001). Both overall survival (OS) and metastasis-free survival (MFS) were significantly worse in the UC with histologic subtype and differentiation group (five-year OS: 48.1 % vs. 73.1 %, p < 0.001; five-year MFS: 58.3 % vs. 87.4 %, p < 0.001). In multivariate analyses, presence of histologic subtypes and LVI were independently associated with poorer OS and MFS across all models. Age remained a significant factor for OS in all categories. ASA score ≥2 and surgical margin positivity were also associated with OS in the overall and muscle invasive patient cohorts.

Histologic subtypes of UC are associated with more aggressive clinicopathologic features and significantly worse survival outcomes. Early and accurate recognition of these subtypes and divergent differentiations at initial TUR-BT is critical, highlighting the need for tailored management strategies to improve patient prognosis.