Clinicopathological characteristics and prognostic outcomes of bladder urothelial neoplasms in patients under 40 years of age: a multicenter retrospective study.

Bladder cancer is rare in patients under 40 years of age, and its clinicopathological behavior in this demographic remains a subject of debate. This study aimed to evaluate the histopathological features and prognosis of bladder tumors in patients under the age of 40. This multicenter retrospective study included bladder transurethral resection, biopsy, and cystectomy samples obtained from patients younger than 40 years of age across 20 centers in Turkiye between 2010 and 2025. Among 1,555 biopsies, 445 patients were diagnosed as urothelial neoplasms. After exclusion of 45 patients lacking hematoxylin and eosin stained slides for re-evaluation, 400 urothelial neoplasms were included in the final cohort. All patients were centrally reviewed by three genitourinary pathologists to establish a consensus diagnosis. Demographic characteristics, clinical presentation, tumor localization, pathological stage, and histological subtypes were analyzed. Follow-up data were available for 206 patients and were used to evaluate clinical outcomes. Statistical analyses were performed using chi-square tests with post-hoc analysis based on adjusted standardized residuals. Low-grade papillary urothelial carcinoma (LGPUC) was the most frequent diagnosis, accounting for 233/400 patients (58.3%), followed by papillary urothelial neoplasm of low malignant potential (PUNLMP) in 55/400 patients (13.8%) and high-grade papillary urothelial carcinoma (HGPUC) in 32/400 patients (8.0%). Overall, 340/400 tumors (85.0%) were non-invasive, whereas 60/400 tumors (15.0%) were invasive. Hematuria was the most common presenting symptom, observed in 197/400 patients (49.3%). Diagnostic revisions after central review were identified in 127/400 patients (31.8%), most commonly involving reclassification between PUNLMP and LGPUC. Age-group analysis demonstrated that urothelial neoplasms occurred most frequently in the 31-40-year age group, which showed a significantly higher proportion of HGPUC and invasive tumors (p < 0.001). Subtype histology or divergent differentiation was identified in 4/60 invasive tumors (6.7%). Among the 206 patients with available follow-up data, remission was observed in 159/206 patients (77.2%), recurrence in 41/206 (19.9%), progression in 2/206 (1.0%), and death in 4/206 patients (1.9%). Adverse clinical outcomes were largely confined to invasive tumors. Bladder tumors in patients under 40 years of age typically exhibit low-grade, low-stage characteristics with a favorable prognosis. Consistent with the literature, the 31-40 age group appears to be a biological transition zone with increased risks of high-grade and invasive carcinoma. Long-term follow-up remains essential due to the potential for recurrence and progression in specific subtypes.