Long-Term Outcomes of Laparoscopic Nephroureterectomy with Transurethral Circumferential Excision of the Ureteral Orifice for Urothelial Carcinoma

Abstract

Introduction:

When performing open or laparoscopic nephroureterectomy (LNU), the optimal way to excise the distal ureter remains controversial. There are concerns that primary endoscopic detachment of the intramural ureter is associated with adverse outcomes. Existing studies have limited number of patients and inadequate oncologic follow-up. We provide our institutions experience of this technique.

Materials and Methods:

Data were collected prospectively on 59 patients (37 men) who underwent LNU for a 10-year period at a single center using a standardized technique: initial endoscopic circumferential release of the distal ureter and bladder cuff followed by retroperitoneal en bloc LNU.

Results:

Patients had a mean age of 67 years and Charlson score of 2. One case was converted to open surgery. Mean operative time was 194 minutes with estimated blood loss of 125 mL. Three patients (5%) required a blood transfusion. Mean in-patient stay was 3 days. Forty-six patients had urothelial carcinoma. Seventy-one percent of patients had high-grade disease (n = 33) and 21% had distal ureteral disease (n = 10). One patient required open excision of recurrence at the site of the excised ureteral orifice and remains disease free 5 years later. Five-year cancer-specific survival was 100% for patients with stages pTa (n = 7) and pT1 (n = 14), 93% for stage pT2 (n = 7) disease, and 49% for patients with stage pT3 (n = 18) disease.

Conclusions:

Transurethral resection of the ureteral orifice during LNU achieves acceptable long-term oncologic outcomes while minimizing perioperative morbidity and in-patient stay. This represents the largest single-center study of this technique to date.

Introduction

It is well established that removal of the ipsilateral kidney, ureter, and bladder cuff is the oncologic gold standard in patients with large volume, high grade, or invasive upper urinary tract urothelial carcinoma (UTUC). Laparoscopic nephroureterectomy (LNU) has been shown to have equivalent oncologic outcomes to open nephroureterectomy.^1,2 However, the “standard” technique of LNU is not defined and, in particular, management of the distal ureter remains contentious. In 1952, McDonald et al. advocated endoscopic release of the distal ureter to minimize perioperative morbidity.³ However, this “pluck” technique has perceived theoretical risks such as extravesical urine spillage, tumor seeding, and therefore, increased risk of pelvic recurrence. Retrospective studies have shown conflicting results, with some showing increased levels of pelvic recurrence and others showing equivalent oncologic outcomes. Existing studies are restricted to small number of patients and limited oncologic follow-up. This study evaluates the perioperative and oncologic outcomes in a large, single-center experience with long follow-up.

Materials and Methods

Between November 2005 and August 2015, 59 consecutive LNUs were performed at our institution, including 46 for pathologically confirmed UTUC. Demographic, operative, and postoperative parameters were analyzed from a prospectively maintained electronic database. Results of follow-up evaluations as well as overall recurrence-free and cancer-specific survival (CSS) data were retrospectively obtained from patient notes.

Surgical technique

The initial step was performed cystoscopically. The affected ureteral orifice was cauterized to prevent urine spillage. This was followed by transurethral circumferential excision of the ureteral orifice to perivesical fat using a Colling's knife. A laparoscopic retroperitoneal nephroureterectomy was subsequently undertaken. Remaining blunt pelvic dissection and removal of specimen en bloc was undertaken through an extended medial port site, with the patient kept in the lateral decubitus position. The remaining pelvic dissection of ureter is undertaken extraperitoneally. The bladder was left to heal by secondary intention. A urethral urinary catheter was subsequently kept in place for 10 days and, in patients with urothelial carcinoma, a single instillation of mitomycin-C was given before removal of the catheter. We do not routinely perform a cystogram before catheter removal.

Follow-up

Patients were followed up with cystoscopy and cytology initially at 3 months and subsequently yearly, with at least yearly upper tract imaging in accordance with EAU guidelines.

Statistical analysis

Statistical analyses were performed using Graph Pad Prism version 7 and SPSS version 16. Kaplan–Meier survival methodology was used to generate survival curves. We used a Cox proportional hazard analysis to assess the impact of prognostic factors upon survival.

Results

A total of 59 patients underwent LNU. Mean patient age was 67 years and the median Charlson comorbidity score was 2. Median American Association of Anesthesiologist Score was 2. None of the patients received neoadjuvant chemotherapy before surgery. Table 1 lists patient demographic and preoperative characteristics. Three patients had adjuvant chemotherapy.

Table 1.

Patient Demographics and Perioperative Outcomes

No. of patients	59
No. of men (%)	38 (64)
Age, year, mean ± SD	67 ± 10.3
Median ASA	2
Operative time mean ± SD	194.4 ± 63.3
Estimated blood loss, mL, mean ± SD	125 ± 136
Hospital stay, days, mean ± SD	3.4 ± 2.6
Conversion to open	1
Length of urinary catheter, mean ± SD	10.9 ± 2.8

ASA = American Association of Anesthesiologists; SD = standard deviation.

Mean hospital stay was 3 days. One patient required open conversion because of bleeding. Two patients (3%) had complications more than Clavien grade 2. Both had grade 3b complications, with one requiring to go back to theatre on the second postoperative day for an incarcerated port site hernia. The other patient had a splenic injury, requiring laparotomy and splenectomy. Three patients (5%) required blood transfusion.

Forty-six patients had pathologically confirmed UTUC. High-grade lesions were present in 33 patients (72%). Tumor was located in the pelvicaliceal system in 23 patients, the proximal ureter in 9 patients, and the distal ureter in 10 patients. Four patients had multifocal disease (Table 2).

Table 2.

Pathology Report

No. of patients with TCC	46
No. of T stages
Ta	7
T1	14
T2	7
T3	18
Mean tumor size (range, cm)
No. of tumor location
Ureteral	19
Pelvicaliceal	23
Pelvicaliceal + ureteral	4
Tumor grade
G1	17
G2	6
G3	33
No. of positive surgical margin	3

Pathologic stage was pTa in 7 patients, pT1 in 14, pT2 in 7, and pT3 in 18 patients. Three patients (7%) had positive surgical margins, which were perinephric in 1 (high-grade pT3, renal pelvis), proximal ureteral in 1 (high-grade pT3), and distal ureteral in 1 (low-grade pTa).

Follow-up data were available for all patients at the time of writing of this article. Median follow-up was 58 months. Five-year overall survival rate was 51% (Fig. 1), CSS rate was 80%, and recurrence-free survival rate was 49%. Five-year CSS by stage was 100% for pTa, 100% for pT1, 93% for pT2, and 49% for pT3 (Fig. 2).

FIG. 1.

Overall survival according to stage.

FIG. 2.

Cancer -specific survival according to stage.

Recurrence developed in 17 patients (37%) at a median of 13 months. Of the recurrences, nine (53%) were urothelial and eight (47%) were nonurothelial, including pelvic recurrence in one patient and retroperitoneal recurrence in another. The patient with pelvic recurrence required open excision of recurrence at the site of the excised ureteral orifice and remains disease free 5 years later. There were no port site recurrences. Distal ureteral outcomes and pathology analysis were comparable with overall results (Table 3).

Table 3.

Distal Ureter Pathology Report and Outcomes

No. of patients with distal ureteral TCC	16
No. of T stages
Ta	3
T1	4
T2	2
T3	7
Tumor grade
G1	5
G2	2
G3	9
Recurrences (urothelial, nonurothelial)	5 (3, 2)
Median time to recurrence (months)	12
Five-year CSS	81%

CSS = cancer-specific survival.

On univariate analysis, tumor stage (p = 0.02) and grade (0.04) adversely affected CSS. On multivariate analysis, only tumor stage (p = 0.04) was negatively associated with CSS.

Discussion

Endoscopic detachment of the intramural ureter during radical nephroureterectomy is a technique that has been plagued by concerns over local urine extravasation and subsequent tumor recurrence.^4,5 There is, however, a sparsity of high-quality evidence confirming any oncologic inferiority. This study represents long-term, single-center data, showing that this technique achieves acceptable long-term oncologic outcomes while minimizing perioperative morbidity and in-patient stay.

Prior studies on this topic have shown conflicting results. As early as 1986, Hetherington and colleagues described their case series of five patients treated with endoscopic management of the intramural ureter. Of these five patients, two developed recurrence at the site of the excised ureter orifice.⁶ More recently, Ko and colleagues, in their study of 51 patients undergoing LNU, had 5 patients who required unplanned incomplete ureterectomy.⁷ A multicenter study comparing differing methods of managing the distal ureter, including 85 managed endoscopically, showed higher rates of intravesical recurrence for the endoscopic technique but no difference in CSS.⁸ However, other studies have shown equivalence for the endoscopic technique. Walton et al. compared 90 patients managed with endoscopic release with 43 managed with open excision, and showed equivalent oncologic outcomes and reduced operative time for the endoscopic group at 43 months follow-up.⁹ Similarly Salvador-Bayarri and colleagues compared open nephroureterectomy with open bladder cuff excision with endoscopic management and showed no statistically significant difference in bladder recurrence or CSS.¹⁰ A multicenter study by El Fettouh et al. showed that intravesical recurrence and metastases were associated primarily with pathologic stage, irrespective of the technique for excision of the distal ureter.¹¹

Our 5-year CSS of 80% and recurrence rate of 37% compare favorably with other laparoscopic studies, including Berger and colleagues (CSS = 78%, recurrence rate = 52%) and Margulis et al. in their multi-institutional study (CSS = 73%, recurrence rate = 31%).^12,13 Similarly, our major complication rate of 3% and length of stay, 3 days, compare favorably with other laparoscopic series (3.8%, 6 days).^14,15

The main limit of our study is its retrospective nature and the lack of a control group. However, this is mitigated by the fact that the nature of upper tract urothelial cancer means that large randomized prospective studies are not feasible. The main strength of our study is the long follow-up of this single technique and that it was conducted at a single center.

The lack of evidence against endoscopic detachment of the intramural ureter is reflected in a recent change in European Urology guidelines, which now state that, apart from ureteral stripping, none of the techniques for managing the distal ureter has been shown to be inferior to open bladder cuff excision.¹⁶

This study confirms the conclusions of those guidelines and demonstrates that the technique of endoscopic detachment of the ureter before LNU achieves truly durable acceptable oncologic outcomes with low levels of pelvic recurrence and the expected minimal related morbidity as one would expect for a minimally invasive procedure.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

Abbreviations Used

References

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