Purpose. To describe the natural history and identify predictors of cancer-specific survival in patients who experience disease recurrence after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Methods. Of 2,494 UTUC patients treated with RNU without neoadjuvant chemotherapy, 597 patients experienced disease recurrence. A total of 148 patients (25 %) received adjuvant chemotherapy before disease recurrence. Multivariable Cox regression model addressed time to cancer-specific mortality after disease recurrence. Results. The median time from RNU to disease recurrence was 12 months (interquartile range 5-22). A total of 491 (82 %) of 597 patients died from UTUC, and 8 patients (1.3 %)died from other causes. The median time from disease recurrence to death of UTUC was 10 months. Actuarial cancer-specific survival estimate at 12 months after disease recurrence was 35 %. On multivariable analysis that adjusted for the effects of standard clinicopathologic characteristics, higher tumor stages [hazard ratio (HR) pT3 vs. pT0-T1: 1.66, p = 0.001; HR pT4 vs. pT0-T1: 1.90, p = 0.002], absence of lymph node dissection (HR 1.28, p = 0.041), ureteral tumor location (HR 1.44, p<0.0005) and a shorter interval from surgery to disease recurrence (p <0.0005) were significantly associated with cancer-specific mortality. The adjusted 6-, 12- and 24-month postrecurrence cancer-specific mortality was 73, 60 and 57 %, respectively. Conclusions. Approximately 80 % of patients who experience disease recurrence after RNU die within 2 years after recurrence. Patients with non-organ-confined stage, absence of lymph node dissection, ureteral tumor location and/or shorter time to disease recurrence died of their tumor more quickly than their counterparts. These factors should be considered in patient counseling and risk stratification for salvage treatment decision making.
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