Prognostic Factors for Contralateral Recurrence of Upper Tract Urothelial Carcinoma after Nephroureterectomy: A Large Multiregional Study

Simple Summary Recurrence of cancer on the opposite side after the removal of primary upper tract urothelial carcinoma (UTUC) is uncommon, but the risk of subsequent deterioration of kidney function may be severe and result in the need for permanent dialysis. There is a clear correlation between inflammation and tumor development in patients with cancer. As the presence of white blood cells (WBC) in urine is an indicator of local inflammation and a biomarker for bladder recurrence of UTUC, we hypothesized that systemic inflammation is involved in the occurrence of contralateral lesions. We proved that elevated serum WBC, late chronic kidney disease, and multiple tumors are independent prognostic factors for contralateral recurrence. Moreover, in a subgroup analysis, the importance of chronic kidney disease in contralateral recurrence was demonstrated for the first time in a non-Asian population. It is recommended that high-risk patients be closely followed up to monitor the opposite upper urinary tract. This study aimed to examine the prognostic significance of preoperative inflammation-associated blood cell markers in the metachronous contralateral recurrence of upper tract urothelial carcinoma (UTUC). Patients with nonmetastatic UTUC treated in Taiwan and the U.S. between 1990 and 2017 were included. The Kaplan-Meier method was used to calculate the contralateral recurrence rate, and multivariate logistic regression was performed to study the association of blood cell markers and clinicopathological characteristics with contralateral recurrence. Overall, a total of 1039 patients were included in this study, 52 of whom (5.0%) developed metachronous recurrence of the contralateral side. Kaplan-Meier analysis indicated that a history of bladder cancer (p = 0.006), multiple tumors (p = 0.016), advanced chronic kidney disease (CKD; p < 0.001), elevated serum white blood cell (WBC) count (p < 0.001), and decreased hemoglobin levels (p = 0.001) significantly reduced the contralateral recurrence-free survival. Multivariate analysis showed that multiple tumors (hazard ratio (HR), 1.87; p = 0.030), advanced CKD (HR, 2.63; p = 0.002) and increased WBC count (HR, 2.60; p = 0.001) were independent risk factors for higher contralateral recurrence rate. Notably, advanced CKD was a significant factor regardless of the patient's region. In summary, multiple tumors, advanced CKD and elevated serum WBC count are independent predictors of contralateral recurrence in patients with UTUC. It is recommended that patients with these adverse characteristics be closely followed up to monitor the opposite upper urinary tract.