The oncological results of laparoscopic nephroureterectomy for upper urinary tract transitional cell cancer are equal to those of open nephroureterectomy

Authors


Matthias Waldert, Department of Urology, Medical University of Vienna, Waehringerguertel 18-20, 1090 Vienna, Austria.e-mail: matthias.waldert@meduniwien.ac.at

Abstract

OBJECTIVE

To compare the overall, tumour-specific, recurrence-free, and progression- free survival of patients with upper urinary tract transitional cell carcinoma (UUT-TCC) treated with laparoscopic nephroureterectomy (LNU) or standard open NU (ONU).

PATIENTS AND METHODS

Clinical, pathological and follow-up data were analysed for 43 LNUs and 59 ONUs performed at our institution from 1999 to 2006. In LNU the kidney was removed laparoscopically as in radical nephrectomy, but without transecting the ureter. The specimen was then removed intact with the entire ureter and a bladder cuff through a nonmuscle-splitting supra-inguinal incision. ONU was performed through separate intercostal and supra-inguinal incisions with the entire specimen being removed intact with a bladder cuff through the latter.

RESULTS

The mean (sd) follow-up was 41 (20) months for LNU and 41 (29) for ONU. Pathological staging was: pTa 26% vs 20%, pT1 21% vs 27%, pT2 12% vs 17%, pT3 42% vs 34% for LNU and ONU, respectively. In all, seven vs six patients had positive nodes on final histology. Recurrent tumours in the bladder were detected in 26% of patients after LNU and in 27% after ONU after the mean follow-up. There were no local recurrences after LNU but there was local recurrence in six patients after ONU. There were no port-site metastases during the follow-up. Five LNU patients and seven ONU patients developed distant or lymph node metastasis. The actuarial 5-year tumour free-survival rate was 79% in the LNU group vs 76% in the ONU group (P = 0.82). The actuarial disease-specific survival at 5-years was 85% for LNU and 80% for ONU patients (P = 0.62). The surgical approach did not influence recurrence or survival.

CONCLUSION

Oncological results of LNU and ONU are comparable. The lower morbidity of LNU offers advantages for the patient.

Abbreviations
UUT

upper urinary tract

(O)(L)NU

(open) (laparoscopic) nephroureterectomy

EBL

estimated blood loss

LND

lymph node dissection.

INTRODUCTION

Upper urinary tract TCC (UUT-TCC) accounts for ≈5% of urothelial carcinomas. Because of its high potential for progression open nephroureterectomy (ONU) has been the standard method of treatment [1]. For the treatment of RCC laparoscopic radical nephrectomy is increasingly being used because of its lower morbidity with similar oncological results. For the same reasons laparoscopic NU (LNU) has attracted considerable interest but the treatment of the distal ureter remains under debate [2,3]. TCC has been shown to have a significantly higher risk of local spread at surgical management. Therefore, LNU must copy the open approach with no surgical compromises, i.e. ‘no-touch’ technique, excision of the entire ipsilateral tract with a bladder cuff as a whole specimen, and no opening of the collecting system. Equivalent short- and intermediate-term tumour control has been reported for LNU but patient numbers are small and they only have a limited follow-up [4–7]. Thus we analysed our 5-year oncological results and clinical outcome in patients with UUT-TCC who underwent consecutive LNU or ONU between 1999 and 2006.

PATIENTS AND METHODS

We retrospectively reviewed the charts of 111 patients who had either ONU or LNU for UUT-TCC at this institution between 1999 and 2006. The choice of method mainly depended on surgeon’s preference. During this period, only nine cases were excluded from LNU because of locally advanced disease and were treated by ONU; they were therefore excluded from this study. Data collected for this study includes patient gender, age, initial symptoms, history of previous TCC and cancer, surgery time, estimated blood loss (EBL), histopathological reports, intra- and postoperative complication rates, and postoperative hospital stay. The follow-up consisted of physical examination, cystoscopy, urinary cytology, serum creatinine measurement and ultrasonography of the remaining kidney every 3 months for the first 2 years and biannually thereafter. An abdominal CT was performed at 3, 6 and 12 months after surgery, and yearly thereafter.

The diagnosis of UUT-TCC was usually established by CT, cytology, retrograde pyelography and in selected cases by ureteroscopy. Our technique of LNU was described previously [8]. Either radical laparoscopic transperitoneal nephrectomy or, with previous abdominal surgery, retroperitoneal radical nephrectomy was performed without dissecting the ureter. For the transperitoneal approach four 12-mm ports were used, and for the retroperitoneal approach three 12-mm and one 5-mm port was used. In all LNUs a voice-controlled robotic arm (AESOP, Computer Motion, USA) was used for camera guidance. For laparoscopic dissection, monopolar scissors (Wolf, Knittlingen, Germay) and bipolar forceps (Ethicon, USA) were used. In LNU a lymphadenectomy was performed in 30/43 patients. A median (range) of 8.4 (4–11) nodes were retrieved from the hilar and ventral caval region on the right side and ventral aortic region on the left side with the psoas muscle as lateral and the iliac vessels as caudal boundaries. After lymph node dissection (LND) the ureter was mobilized to the iliac vessel junction. The kidney was entrapped in a cell-tight organ bag (Rüsch, Kernen, Germany) with no dissection of the ureter, leaving the whole specimen in situ. A 10-cm nonmuscle-splitting incision was made at the site of the port in the lower abdomen for dissection of the distal ureter and bladder cuff, and subsequent removal of the intact organ. The intramural distal ureter was mobilized beyond the ipsilateral ureteric orifice and removed in toto with a 1 cm bladder cuff using the standard surgical technique. The bladder was incised over a clamp and the distal ureter was cross-clamped before this. The bladder was then sutured before releasing the clamp, so that urine spillage was reliably avoided. The intact specimen was sent for frozen-section analysis to exclude positive margins at the distal bladder cuff.

ONU was performed through a 25–30-cm intercostal incision as in radical retroperitoneal nephrectomy. Similar to the laparoscopic technique a no-touch surgical technique was used. Lymphadenetcomy of a similar extent as in LNU was performed in 47/59 patients. The kidney and ureter were excised including a bladder cuff and removed via a supra-inguinal 10-cm incision as described above for LNU.

In both procedures an 18 F Foley catheter and two wound drains (nephrectomy loge, lower abdomen) were placed.

After surgery all patients were mobilized within 24 h. Wound drains were removed on the second postoperative day and regular alimentation usually started on the second postoperative day after normalization of the bowel function. At 7 days after surgery, a cystogram was taken to exclude bladder leakage; if there was none the catheter was removed the same day.

Survival statistics were calculated using the Kaplan–Meier method. To compare categorical variables Pearson’s chi-square test was used, for comparison of continuous variables Student’s t-test or the Mann–Whitney U-test were used. Prognostic factors were calculated by univariate analysis using the log-rank test. Subsequently a multivariate Cox stepwise regression analysis was performed. For all statistical tests P < 0.05 was considered to indicate statistical significance.

RESULTS

In all, 59 ONUs and 43 LNUs for UUT-TCC were analysed. The patients’ data are given in Table 1. Both groups were similar for age, high-grade disease (P = 0.828), number of patients with >pT2 stage (P = 0.917) and node status (P = 0.994).

Table 1. 
Preoperative patient characteristics of ONU and LNU
VariableONULNU
Patients, n5943
Male/female, n40/1921/12
Mean (sd) age, years68.46 (9.30)65.56 (12.34)
N:
 Side:
  Right3225
  Left2718
 Tumour location:
  Pelvicalyceal3324
  Ureter2015
  Both 6 4
 Initial symptoms:
  Gross haematuria2418
  Flank pain 3 5
  Gross haematuria/flank pain 6 4
  None2616
 Previous bladder TCC
  Yes1513
  No4430

The intra- and perioperative results for the ONU and LNU groups are summarized in Table 2. The operating time as calculated from the time of incision to closure in both groups was lower in the LNU group but this did not reach statistical significance (P = 0.53). The EBL and hospital stay were significantly lower in the LNU group (P < 0.001).

Table 2.  Intra- and perioperative results for ONU and LNU
VariableONULNUP
Mean (SD, range):
 Operating time, min212 (34, 70–240)220 (92, 62–280)0.53
 EBL, mL542 (281, 80–980)300 (59, 50–800)<0.001
 Creatinine, ng/mL
  Before surgery 1.46 (0.74) 1.34 (0.36)0.90
  After surgery 1.82 (1.13) 1.61 (0.35)0.70
 Hospital stay, days 13.8 (4.4, 9–16) 8.1 (2.2, 7–9)<0.001

Two ONU (3%) and one LNU patient (2%) required re-intervention because of postoperative bleeding. The LNU case had to be revised because of bleeding from the lateral umbilical ligament, which was dissected during ureterectomy and bladder cuff removal. Our third LNU patient overall was converted to ONU because of surgical difficulties during renal hilar dissection. The collecting system was opened moderately in three cases of ONU (5%) and once in LNU (2%). The postoperative mortality rate was 0%. The surgical margins were negative at the distal ureter/bladder cuff in all cases after ONU and LNU.

The pathological tumour stage and grade for the groups are shown in Table 3. There were positive nodes in six (10%) patients in the ONU and seven (16%) patients in the LNU group (P = 0.96). The patients who had positive lymph nodes (13 patients) at surgery received systemic chemotherapy with gemcitabine and cisplatin.

Table 3. 
Histopathological results of ONU and LNU
VariableONU (n = 59)LNU (n = 43)
N (%):
 Tumour stage:
 Tis1 (2)0
 pTa12 (20)11 (26)
 pT116 (27)9 (21)
 pT210 (17)5 (12)
 pT320 (34)18 (42)
 Tumor grade:
  14 (7)6 (14)
  231 (53)19 (44)
  324 (41)17 (40)
  401 (2)
 Lymph nodes:
  Nx12 (20)13 (30)
  N041 (70)23 (54)
  N14 (7)7 (16)
  N22 (3)0
Median (range) no. nodes removed5.6 (4–11)8.4 (4–12)
N (%):
 Metastasis:
  M055 (93)41 (95)
  M14 (7)2 (5)
 Multifocal UUT disease10 (17)8 (19)
 Concomitant bladder TCC3 (5)2 (5)

The mean (sd) follow-up in the ONU group was 41 (29) months vs 41 (20) months in the LNU group (P = 0.92).

During this time urothelial recurrence in the bladder developed in 16 of the 59 ONU patients (27%) after a mean (sd) of 14 (15) months. One of them, a patient with diffuse carcinoma in situ had also a recurrence in the contralateral UUT. In the LNU patients, TCC recurred in the bladder in 11 of the 43 patients (26%) after a mean (sd) of 14 (14) months (P = 0.91, Fig. 1A). There were no cases of port-site metastasis during the follow-up.

Figure 1.

A, Recurrence-free survival; B, progression-free survival (local recurrence/lymph node metastasis/distant metastasis); and C, disease-specific survival stratified according to surgical procedure.

Local recurrence in the retroperitoneal space developed in six patients (10%) in the ONU group vs none in the LNU group. There were distant metastasis or lymph node metastasis in seven patients (12%) during follow-up in the ONU group vs five (11%) in the LNU group (P = 0.12 and 0.99, respectively). The six local recurrences in the ONU group all had grade 3, stage pT2 or pT3 disease. The mean (sd) time to progression was 17.00 (14.26) months in the LNU group vs 14.92 (17.21) in the ONU group (P = 0.51, Fig. 1B). The estimated 5-year tumour free-survival rate was 76% in the ONU group vs 79% in the LNU group (P = 0.82).

During the follow-up 21 of 102 (21%) patients died after a mean (sd) of 32 (26) months. Thus, overall survival was 79% and disease-specific survival was 89% (91/102 patients). The mean (sd) time to disease-specific death was 28 (22) months (Fig. 1C). The estimated disease-specific survival at 5 years was 80% for ONU and 85% for LNU patients (P = 0.62).

Prognostic factors were analysed by univariate and multivariate analysis. The results are given in Table 4. On univariate analysis only pT stage, lymph node status, grade and the presence of distant metastasis had an impact on progression-free and tumour-specific survival. At multivariate analysis (whole model test, P = 0.021 and P = 0.035, respectively) tumour stage and tumour grade were independent factors for progression and disease-specific death. The type of surgery was not a significant prognosticator.

Table 4. 
Factors influencing prognosis in UUT-TCC. Univariate and multivariate analysis of progression-free survival (PFS) and disease-specific survival (DSS)
 P (odds ratio)
PFSDSS
Univariate analysis
 Stage – pT0.0260.04
 Grade0.0010.05
 Node status0.0430.02
 Distant metastasis0.0050.04
 Surgical procedure0.390.98
 Previous bladder TCC0.190.88
Multivariate analysis (logistic regression)
 Stage – pT0.011 (2.1)0.023 (2.4)
 Grade0.018 (2.0)0.008 (4.1)
 Node status0.028 (1.9)0.034 (1.8)

DISCUSSION

Several series have shown the technical feasibility and lower postoperative morbidity of LNU with less blood loss, lower transfusion rates, lower duration of hospital stay and faster convalescence for LNU as compared with ONU, regardless of the technique used in LNU for ureter removal [2,8,9].

Despite these evident benefits, if LNU does not provide oncological results equal or better than ONU, it should not be done. Limited data concerning intermediate and long-term oncological efficacy of LNU is available.

We previously reported that LNU can be performed within the same time as ONU but with statistically significantly less EBL, analgesic medication and shorter hospitalization [8]. The operative data and convalescence time in the present study are comparable with previously reported data and confirm a meta-analysis by Rassweiler et al. [4]. The major complication rate in the present series was also similar to that of Rassweiler et al. at 3% vs 6% and 2% vs 8% in ONU and LNU, respectively. The slightly longer hospitalization time compared with reported literature is due to the Austrian sociomedical system, which allows for longer hospital stays.

The modified LNU applied in the present study resulted in less inadvertent opening of the collecting system. This can partially be explained by the fact that the involuntary opening of the collecting system happened mainly in pT2 and pT3 because of local tumour extension and becuase the laparoscopic approach has better magnification and and visualization of structures.

To date only ≈10 cases of port-site metastasis after LNU have been reported [10–13]; none occurred in the present study. In the previous reported cases, removal of the resected organ was done with no organ bag or with a defective organ bag. The remaining cases were explained due to unsuspected TCC, where the strict rules of en bloc removal of the kidney and ureter without opening of the collecting system were not adhered to.

The benefits of LND in cases of UUT-TCC remain controversial [14–16]. Recently an abstract by Busby et al. [15] showed that LND could be performed as well in LNU as in ONU. From our previous experience with micrometastasis in high-grade tumours, we now routinely perform lymphadenectomy in LNU and ONU [8]. In the present study there was no difference in the median number of nodes removed at LNU and ONU. Lymphadenectomy improves staging, but the number of patients with node-positive disease in the present study was too small to draw a definitive conclusion as to whether LND offers a survival benefit or not. It certainly affected further treatment strategy, as all node-positive patients received adjuvant cisplatin/gemcitabine-based chemotherapy. Larger prospective studies are needed to definitively answer the question of lymphadenectomy in UUT-TCC [16]. As LND did not increase postoperative complications or prolong hospital stay, we advocate a routine lymphadenectomy in high-grade/high-stage disease to better tailor postoperative care and therapy.

The 5-year disease-free survival rate of 79% and the 85% cancer specific-survival rate for LNU patients in the present analysis are comparable with previously published data [4–7]. Although not randomized the LNU and ONU groups were comparable for tumour stage and grade, which were shown to be the main factors affecting the development of metastasis and survival. In the ONU group 43% of tumours were stage >pT2 tumours vs 42% in the LNU group. We are able to show equivalent results for midterm cancer-specific and recurrence-free survival in cases of pTa–pT3 malignancies. Advanced stage and grade, not surgical approach were the only factors influencing survival in the present study.

In conclusion, after a mean (sd) follow-up of 40.9 (19.7) months oncological results were comparable after LNU and ONU. Because of the lower morbidity of the laparoscopic approach LNU seems to offer advantages for the patient.

CONFLICT OF INTEREST

None declared.

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