Long-term impact of synchronous and metachronous bladder cancer on prognosis after radical nephroureterectomy for upper urinary tract urothelial carcinoma: results from a large population-based cohort in China

Purpose: This study aimed to evaluate the prognostic significance of synchronous and metachronous bladder cancer (BCa) in Chinese patients with upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). Materials and Methods: We retrospectively analyzed clinicopathological data from 2921 consecutive nonmetastatic UTUC patients who underwent RNU between 2000 and 2022. Kaplan–Meier survival analysis and Cox proportional hazards regression models were employed to assess the impact of synchronous or metachronous BCa on clinical outcomes. Results: The cohort included 118 patients (4.0%) with prior non-muscle-invasive BCa (NMIBCa) only and 205 patients (7.1%) with synchronous NMIBCa. Synchronous NMIBCa showed significant associations with inferior overall survival [OS; hazard ratios (HR) = 1.709, 95% confidence interval (CI): 1.301–2.247] and cancer-specific survival (CSS; HR = 1.577, 95% CI: 1.265–1.967). Multivariate analysis confirmed synchronous NMIBCa as an independent predictor for both OS (HR = 1.709, 95% CI: 1.301–2.247, P < 0.001) and CSS (HR = 1.577, 95% CI: 1.265–1.967, P < 0.001). Neither prior NMIBCa history nor the interval from NMIBCa to UTUC diagnosis showed significant associations with OS or CSS. Of the 2598 patients without prior or synchronous BCa, 491 (18.9%) developed intravesical recurrence after RNU, including 37 (7.5%) cases of muscle-invasive BCa. Among 2598 patients without prior/synchronous BCa, 491 (18.9%) developed intravesical recurrence post-RNU, including 37 (7.5%) muscle-invasive cases. Intravesical recurrence within 1–2 years significantly predicted unfavorable OS and CSS, and muscle-invasive BCa recurrence during this period indicated particularly poor outcomes. Conclusions: Synchronous NMIBCa is an independent risk factor for worse survival in UTUC patients. Early IVR was significantly related to poor survival outcomes in UTUC patients, particularly in pTa-2 cases. Bladder-directed preventive and adjuvant therapeutic strategies may optimize clinical outcomes.