Objectives: To characterize the site and clinical implications of intravesical recurrence after radical nephroureterectomy for upper urinary tract urothelial carcinoma. Methods: Patients who underwent radical nephroureterectomy for upper urinary tract urothelial carcinoma between 2000 and 2011 at 12 institutions participating in the Tohoku Urological Evidence-Based Medicine Study Group were included in the present study. Those who underwent prior or simultaneous radical cystectomy were excluded. The site of intravesical recurrence was investigated, and the survival curves after radical nephroureterectomy were analyzed retrospectively using the Kaplan-Meier method. Multivariate analyses of factors predicting survival were carried out. Results: A total of 534 patients were eligible for the present study. With a median follow up of 47 months, 205 patients (38.4%) had intravesical recurrence. The intravesical recurrence-free survival rates at 1, 2, and 5 years were 74.6%, 62.5% and 56.3%, respectively. In a subset of 137 patients with intravesical recurrence who did not have bladder cancer before or at the diagnosis of upper urinary tract urothelial carcinoma, the most frequent site of intravesical recurrence was around the cystotomy (52.6%), followed by at the posterior wall (39.4%) and at the bladder neck (35.8%). A total of 36 patients (17.6%) developed muscle-invasive bladder cancer after radical nephroureterectomy. On multivariate analyses for the subset of patients with non-muscle invasive (≤pT1) upper urinary tract urothelial carcinoma, intravesical recurrence was an independent predictor of cancer-specific survival (HR 4.27, P = 0.016) and overall survival (HR 3.00, P = 0.018). Conclusions: Most intravesical recurrences occur around the site of bladder mucosal injury within 1 year after radical nephroureterectomy, providing important insight into the mechanism of intravesical recurrence. Intravesical recurrence after radical nephroureterectomy had an impact on oncological outcomes of patients with non-muscle invasive upper urinary tract urothelial carcinoma.
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