Impact of divergent differentiation in urothelial carcinoma on oncological outcome in patients with T1 high-grade bladder cancer

T1Objective: T1 high-grade bladder cancer has a poor prognosis compared with other non-muscle invasive bladder cancers. We investigated the clinical outcomes among patients with T1 highgrade bladder cancer to identify factors related to cancer recurrence and disease progression. Methods: We retrospectively reviewed the data of 148 patients who were diagnosed with T1 highgrade bladder cancer by transurethral resection from January 2001 to February 2015 at our institution. Clinicopathological factors were analyzed using univariate and multivariate analyses. Results: The median age and follow-up duration were 72 years and 45.4 months, respectively. Sixty-two patients (41.9%) had recurrence, 28 (18.9%) experienced progression and 13 (8.8%) died of bladder cancer. In the multivariate analysis, divergent differentiation was an independent factor related to recurrence (P = 0.0096, hazard ratio = 2.5), whereas a non-papillary tumor shape, divergent differentiation and presence of a residual tumor at the time of the second transurethral resection were independent factors related to progression (P = 0.0349, hazard ratio = 3.8; P = 0.0074, hazard ratio = 6.8 and P= 0.0449, hazard ratio = 4.1, respectively). There were no independent factors related to cancer-specific mortality. Divergent differentiation was the only independent factor associated with both recurrence and progression. In addition, patients with divergent differentiation had significantly worse recurrence-free survival and progression-free survival rates than did patients without divergent differentiation (log-rank P = 0.0009 and P = 0.0019, respectively). Conclusions: In this study, the presence of divergent differentiation was related to worse oncological outcomes in patients with T1 high-grade bladder cancer. Patients with divergent differentiation may require stringent follow-up and early cystectomy after recurrence to improve oncological outcomes.