Distal-first versus proximal-first laparoscopic nephroureterectomy for non-muscle-invasive upper tract urothelial carcinoma: a retrospective cohort study

Abstract Background and objective The optimal sequence of ureteral and vascular control during laparoscopic nephroureterectomy (LNU) for non-muscle-invasive (≤ pT1) upper tract urothelial carcinoma (UTUC) remains controversial. We compared distal-first (initial ureteral ligation) and proximal-first (initial renal pedicle control) approaches regarding perioperative safety and intravesical recurrence. Methods Consecutively treated patients with non-muscle-invasive UTUC (≤ pT1) who underwent LNU from 2019 to 2023 were retrospectively enrolled. Exclusion criteria included prior ureteroscopic manipulation, concomitant bladder cancer, stage ≥pT2, incomplete data, or loss to follow-up. Based on operative records, 57 patients underwent a proximal-first and 67 a distal-first approach. All received a single immediate postoperative intravesical instillation of pirarubicin or gemcitabine according to institutional protocol and were followed for up to 2 years. Intravesical recurrence-free survival was estimated by Kaplan-Meier analysis and compared with the log-rank test. A multivariable Cox regression model was used to adjust for age, tumor location, and tumor grade. Results Baseline characteristics were well balanced between groups. Perioperative outcomes, including operative time, estimated blood loss, and hospital stay, did not differ significantly (all P > 0.05). No major complications occurred in either group; minor complications (Clavien-Dindo I–II) were comparable (proximal-first: 14.0% vs. distal-first: 13.4%, P = 0.923). During the 24-month follow-up period, intravesical recurrence occurred in 17 of 57 patients (29.8%) in the proximal-first group versus 11 of 67 (16.4%) in the distal-first group (absolute risk reduction, 13.4%; number needed to treat, 8). The distal-first approach was associated with a numerically lower recurrence rate, but the difference did not reach statistical significance (HR, 2.06; 95% CI, 0.96–4.43; log-rank P = 0.064). The wide confidence interval, which narrowly crosses unity, reflects the limited precision of this estimate. In the pre-specified renal pelvic/upper ureteral tumor subgroup ( n = 63), recurrence rates were 28.6% (8/28) versus 11.4% (4/35), yielding an absolute risk reduction of 17.1% and a number needed to treat of 6 (HR, 2.78; 95% CI, 0.87–8.87; log-rank P = 0.085). After multivariable adjustment, the association was attenuated (aHR, 1.27; 95% CI, 0.57–2.83; P = 0.561). Conclusions In this retrospective cohort study, both distal-first and proximal-first LNU achieved comparable perioperative safety. The distal-first strategy, by ligating the terminal ureter at the bladder insertion before renal mobilization, better adheres to the no-touch principle. Although a trend toward reduced intravesical recurrence was observed, this did not reach statistical significance and was attenuated after multivariable adjustment. The wide confidence intervals preclude definitive conclusions regarding the magnitude of clinical benefit. These findings warrant prospective validation in a multicenter randomized trial.