Introduction

Intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC) occurs at a high rate. We previously reported that most IVR occurs around the site of damage to the bladder mucosa within one year of RNU and that IVR after RNU affects the oncological outcomes of patients with non-muscle invasive UTUC. Seeding of UTUC cells on the damaged bladder wall during RNU is considered to be a cause of IVR. Thus, efficacy of early ureteral ligation (EUL) on prevention of IVR after RNU for UTUC was prospectively evaluated in a multicenter clinical trial.

Methods

Patients who underwent RNU for UTUC between 2012 and 2013 at 15 institutions participating in the Tohoku Urological Evidence-Based Medicine Study Group were enrolled. Those with bladder cancer before RNU or metastasis at the time of UTUC diagnosis were excluded. We defined EUL as ligating the ureter as soon as possible after expanding the retroperitoneal space and before ligating the renal artery. A historical control was extracted from 454 patients from the same group who underwent RNU for UTUC between 2000 and 2011, using propensity score-matched analysis. The IVR-free survival rates following RNU were prospectively analyzed using Kaplan-Meier curves and the log-rank test. Factors predicting IVR were assessed using multivariate analyses. The Ethics Committee at Tohoku University Hospital approved the study protocol.

Results

Seventy-four of the 148 patients had EUL and 74 patients in the control group did not undergo ureteral ligation. With a median follow-up of 21 months, 17 (23%) patients in the EUL group had IVR. The 1- and 2-year IVR-free survival rates in the EUL and control groups were 81% and 76%, respectively and 75% and 63%, respectively (p=0.201). The 1- and 2-year IVR-free survival rates among patients with renal pelvic cancer in the EUL and control groups were 89% and 86%, respectively and 74% and 64%, respectively (p=0.032). However, IVR-free survival rates were similar among the patients with ureteral cancer. Multivariate analyses of a subset of patients with renal pelvic cancer selected EUL as an independent predictor of IVR after RNU (hazard ratio, 0.37; p=0.049).

Conclusions

Early ureteral ligation decreased the rate of IVR after RNU among patients with renal pelvic cancer. This might result from the prevention of floating UTUC cells during RNU. Thus, EUL might contribute to the prevention of IVR after RNU for renal pelvic cancer.

Funding

none