Surgeons comparing two ways of sequencing a kidney-removal operation for upper urinary tract cancer have found that the order in which they tie off the ureter makes no measurable difference to operative time, blood loss, hospital stay, or complications, but may be linked to fewer tumors reappearing in the bladder afterward. The finding, however, comes with a heavy dose of statistical caution: the difference in recurrence did not reach significance, and it largely faded once the researchers adjusted for other factors.
The study, published in the African Journal of Urology, is a retrospective cohort analysis of 124 patients treated at a single center between January 2019 and December 2023. All had non-muscle-invasive upper tract urothelial carcinoma, meaning tumors confined to the lining of the renal pelvis or ureter at stage pT1 or below. Each patient underwent laparoscopic nephroureterectomy with bladder cuff excision, the standard radical treatment for this disease. Fifty-seven patients were operated on with a proximal-first approach, in which the renal pedicle is controlled and the kidney mobilized before the ureter is dealt with. Sixty-seven underwent a distal-first approach, in which the terminal ureter is dissected and ligated at its insertion into the bladder first, followed immediately by excision of the bladder cuff, with attention turning to the renal hilum only afterward.
The rationale for the distal-first sequence rests on the no-touch oncological principle. By clipping the ureter at the bladder before any renal manipulation begins, the surgeon theoretically blocks detached tumor cells from being washed down the urinary tract into the bladder by the flow of urine during the operation. The proximal-first approach, by contrast, facilitates renal mobilization but may increase the risk of tumor manipulation and cell seeding. A theoretical counterargument has long held that early ureteral ligation could make renal dissection harder, because acute obstruction of urinary drainage might cause hydronephrosis, perinephric edema, and increased renal parenchymal tension.
On the perioperative side, the new data offer reassurance against that concern. Operative time, estimated blood loss, and postoperative hospital stay did not differ significantly between the groups, with all comparisons yielding P values above 0.05. No major complications, defined as urinary spillage, intraoperative transfusion, or conversion to open surgery, occurred in either group. Minor complications of Clavien-Dindo grade I to II, which included urinary tract infection, lymphatic leakage, and superficial wound infection, all resolved with conservative management or oral antibiotics, and occurred at nearly identical rates: 14.0 percent in the proximal-first group and 13.4 percent in the distal-first group. No complication of grade III or higher was recorded. The authors attribute this comparable safety profile partly to the fact that renal dissection in the distal-first approach is typically completed within roughly two hours of ureteral clipping, a window in which significant hydronephrosis and perinephric edema are unlikely to develop, and partly to the standard dissection plane outside Gerota’s fascia, modern energy devices, and high-definition laparoscopic systems.
The oncological picture was more ambiguous. During 24 months of follow-up, intravesical recurrence, confirmed by cystoscopy and histology, occurred in 17 of 57 patients, or 29.8 percent, in the proximal-first group, versus 11 of 67 patients, or 16.4 percent, in the distal-first group. That corresponds to an absolute risk reduction of 13.4 percentage points and a number needed to treat of 8. The hazard ratio of 2.06 favoring the distal-first approach carried a 95 percent confidence interval of 0.96 to 4.43, which narrowly crosses unity, and the log-rank P value of 0.064 fell short of the conventional threshold for statistical significance. The authors are explicit that the wide interval reflects the limited precision of the estimate given the modest number of events.
In a pre-specified subgroup of 63 patients whose tumors arose in the renal pelvis or upper ureter, the numerical trend was stronger: recurrence occurred in 8 of 28 patients, or 28.6 percent, with the proximal-first approach versus 4 of 35 patients, or 11.4 percent, with the distal-first approach, an absolute risk reduction of 17.1 percentage points and a number needed to treat of 6. Even here, the confidence interval was wide, spanning 0.87 to 8.87, and the log-rank P value of 0.085 was not significant. The authors note that for distal ureteral tumors, a proximal-first approach does not involve direct manipulation of the tumor-bearing segment, so the theoretical advantage of early ligation is diminished in that location, which is consistent with the stronger subgroup trend.
After multivariable adjustment for age, tumor location, and tumor grade, the association was substantially attenuated. The adjusted hazard ratio for proximal-first versus distal-first was 1.27, with a 95 percent confidence interval of 0.57 to 2.83 and a P value of 0.561. The interval spans effects ranging from potentially protective to potentially harmful, and the authors state that this substantial uncertainty suggests the unadjusted trend may partly reflect confounding, possibly by tumor biology. The model was deliberately restricted to three covariates because only 28 recurrence events occurred, a constraint meant to avoid overfitting, but it also meant that factors such as sex, multifocality, and pathological stage could not be included simultaneously.
The study’s design carries important limitations that the authors themselves enumerate. Allocation of surgical sequence was not randomized but determined by the operating surgeon’s preference and experience, and because the study is retrospective, the reasoning behind each surgeon’s choice cannot be fully reconstructed; unmeasured factors, including individual surgeon assessments of tumor dissemination risk based on imaging and cytology, may have influenced the decision. The single-center design, the modest sample size, and the five-year span during which equipment and perioperative care may have gradually improved all add uncertainty. Follow-up was limited to two years, precluding assessment of long-term survival and contralateral upper tract recurrence, and cystoscopic surveillance did not routinely use narrow-band imaging, which may have limited detection of small or flat bladder lesions. Local recurrence was not systematically evaluated as a separate endpoint, although no definite local recurrence events were observed. The authors also acknowledge that they lack preoperative histological grading, since diagnosis at their institution relies on CT urography and urinary cytology rather than diagnostic ureteroscopy, and that their proposed mechanism of tumor cell detachment and urine-mediated dissemination remains theoretical because no direct cytological or histological evidence of intraoperative dissemination was collected.
Several contextual factors may also have shaped the results. All patients received a single immediate postoperative intravesical instillation of pirarubicin or gemcitabine within 24 hours of surgery, according to institutional protocol and consistent with current European Association of Urology guidelines, which recommend postoperative intravesical chemotherapy to reduce bladder recurrence after nephroureterectomy. The authors suggest that this uniform prophylaxis may have lowered the overall event rate and thereby attenuated the observable difference between surgical sequences, meaning that in settings without routine instillation the absolute benefit of early ureteral ligation might be greater. Baseline characteristics, including age, sex, body mass index, pathological stage, tumor grade, and tumor location, were well balanced between the groups, and the distribution of tumor locations was statistically similar, with a P value of 0.984, indicating no obvious selection bias by tumor site.
The authors position their findings as hypothesis-generating rather than practice-changing. Both approaches achieved comparable perioperative safety, and the distal-first strategy better adheres to the no-touch principle by ligating the terminal ureter before renal mobilization, but the recurrence trend did not reach statistical significance and was attenuated after adjustment. They call for a well-designed, multicenter randomized trial with extended follow-up to determine definitively whether the order of ureteral and vascular control during laparoscopic nephroureterectomy can influence oncological outcomes for patients with non-muscle-invasive upper tract urothelial carcinoma. Until such a trial is completed, the choice of surgical sequence remains, on current evidence, a matter of surgeon judgment rather than established oncological benefit.
Subject of Research: Surgical sequencing during laparoscopic nephroureterectomy for non-muscle-invasive upper tract urothelial carcinoma and its effect on perioperative safety and intravesical recurrence
Article Title: Distal-first versus proximal-first laparoscopic nephroureterectomy for non-muscle-invasive upper tract urothelial carcinoma: a retrospective cohort study
Article References: Wang, M., Liu, J., Li, Q., Zhang, Z., & Shi, J. (2026). Distal-first versus proximal-first laparoscopic nephroureterectomy for non-muscle-invasive upper tract urothelial carcinoma: a retrospective cohort study. African Journal of Urology, 32(1), Article 65. https://doi.org/10.1186/s12301-026-00610-5
Image Credits: AI Generated
DOI: 10.1186/s12301-026-00610-5
Keywords: upper tract urothelial carcinoma, laparoscopic nephroureterectomy, distal-first approach, proximal-first approach, intravesical recurrence, no-touch principle, bladder cuff excision, retrospective cohort study, perioperative outcomes, Clavien-Dindo complications, intravesical chemotherapy, surgical sequencing
News Source: Nathaniel Bowman. (October 29, 2026). Early ureter ligation during kidney cancer surgery shows a hint of benefit, but the evidence stays uncertain. Scienmag.
