Cancer-specific mortality in secondary bladder cancer after nephroureterectomy for upper tract urothelial carcinoma

Objective To examine differences in cancer-specific mortality (CSM) in nonmetastatic upper tract urothelial carcinoma (UTUC) patients with vs. without secondary bladder cancer (BCa) after radical nephroureterectomy (RNU). Methods Within the Surveillance, Epidemiology, and End Results database (SEER 2000–2021), T1-T4N0M0 UTUC patients treated with RNU and diagnosed with secondary BCa were identified. A landmark approach was used, requiring the diagnosis of secondary BCa within 18 months of the UTUC diagnosis. Additionally, a minimum follow-up of 18 months after the UTUC diagnosis was required. Subsequently, Kaplan-Meier plots and time-dependent multivariable Cox regression (MCR) models were fitted. Sensitivity analyses were performed in patients with late BCa diagnoses (6 to 18 months after UTUC diagnosis). Results Of 3,013 eligible UTUC patients who fulfilled the landmark and follow-up criteria, 269 (9.0%) harbored secondary BCa. Ten-year CSM-free survival rates were respectively 60 vs 73% in patients with vs without secondary BCa. In MCR models, secondary BCa independently predicted higher CSM (hazard ratio [HR]: 1.53, p < 0.001). Subgroup analyses by tumor stage confirmed the independent predictor status of secondary BCa in T1−T2 stages (HR: 2.04, p < 0.001), primary renal pelvic (HR: 1.47, p = 0.003) and ureteral (HR: 1.63, p = 0.01) UTUC. Sensitivity analyses confirmed the independent predictor status of secondary BCa also in patients with late secondary BCa (HR: 1.68, p < 0.001). Conclusion In general, secondary BCa in UTUC patients treated with RNU is associated with higher CSM. This disadvantage primarily affects patients with T1–T2 stage UTUC involving the ureter or renal pelvis.