Cumulative incidence and risk factors for recurrence of upper tract urothelial carcinoma in patients undergoing radical cystectomy

Abstract

Objectives: This study aimed to evaluate the cumulative incidence of upper tract urothelial carcinoma (UTUC) recurrence and identify its risk factors in patients who underwent radical cystectomy (RC).

Patients and methods: We performed RC on 385 patients between September 2002 and February 2020. After excluding 20 patients-13 with simultaneous nephroureterectomy, 6 with distal ureteral stump positivity and 1 with urachal cancer-365 patients were included in the analysis. To predict UTUC recurrence, we examined the cancer extension pattern in cystectomy specimens and categorized them into three types: cancer located only in the bladder (bladder-only type), cancer extending to the urethra or distal ureter (one-extension type) and cancer extending to both the urethra and distal ureter (both-extension type). We determined hazard ratios for UTUC recurrence for each covariate, including this cancer extension pattern.

Results: Of the 365 patients, 60% had the bladder-only type, 30% had the one-extension type and 10% had the both-extension type. During a median follow-up period of 72 months for survivors, UTUC recurred in 25 of the 365 patients, with cumulative incidences of 3.7% at 5 years and 8.3% at 10 years. The median interval from cystectomy to recurrence was 65 months (interquartile range: 36-92 months). In the multivariate analysis, the extension pattern was a significant predictor of UTUC recurrence. The hazard ratios for UTUC recurrence were 3.12 (95% confidence interval [CI] = 1.15-8.43, p = 0.025) for the one-extension type and 5.96 (95% CI = 1.98-17.91, p = 0.001) for the both-extension type compared with the bladder-only type.

Conclusions: The cancer extension pattern in cystectomy specimens is predictive of UTUC recurrence. A more extensive cancer extension in cystectomy specimens elevates the risk of subsequent UTUC recurrence. Intensive long-term monitoring is essential, particularly for patients with the both-extension type.

Keywords: bladder cancer; classification; radical cystectomy; recurrence; upper urinary tract.

FIGURE 1

Proportions of three types among 365 cystectomy specimens based on cancer extension patterns: 217 patients (60%) had cancer located only in the bladder, 110 patients (30%) had one‐extension type (either the urethra or distal ureter) and 38 patients (10%) had both‐extension type (the urethra and distal ureter).

FIGURE 2

Cumulative incidence of upper tract urothelial carcinoma (UTUC) after radical cystectomy in 365 patients. (A) UTUC recurrence was observed in 25 out of 365 patients. The cumulative incidences of UTUC recurrence were 3.7% at 5 years and 8.3% at 10 years. (B) Cumulative incidences of UTUC recurrence for patients with cancer located only in the bladder (n = 217) were 1.5% at 5 years and 3.8% at 10 years. For patients with cancer extending to the urethra and/or distal ureter (n = 148), the rates were 6.8% at 5 years and 14.9% at 10 years (p < 0.001, Gray's test). (C) For patients with the one‐extension type (either the urethra or distal ureter, n = 110) and the both‐extension type (both the urethra and distal ureter, n = 38), the cumulative incidence rates of UTUC recurrence were 5.0% and 13.2% at 5 years and 13.9% and 18.8% at 10 years, respectively (p < 0.001, Gray's test).