Robotic-Assisted Laparoscopic Nephroureterectomy

Updated: Nov 29, 2016
  • Author: Chad R Tracy, MD; Chief Editor: Edward David Kim, MD, FACS  more...
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Background of Upper Tract Transitional Cell Carcinoma


Upper urinary tract transitional cell carcinomas (TCCs) are relatively rare, accounting for 5-7% of all renal tumors and 5% of all urothelial tumors. [1] They rarely manifest before the age of 40 years, and the mean age at presentation is 65 years. [2] Men and whites are twice as likely to develop upper tract TCC as compared to women and African Americans. [3] Individuals with a history of bladder cancer are at risk for upper tract recurrence, with a further increase in patients with carcinoma in situ (CIS) (rather than patients with superficial TCC) and in patients treated with cystectomy for CIS (rather than for invasive bladder cancer). [4]

Although most series report the risk of upper tract recurrence to be 2-4% in patients with a previous history of bladder cancer, [4, 5] some have reported rates as high as 21% after a median interval of 7.3 years. [6] Individuals with a history of bladder cancer have been recommended to undergo rigorous upper tract surveillance for an extended (>10 years) period of time to rule out upper tract recurrence. [5]

Symptoms and Signs

See the list below:

  • Hematuria (microscopic or gross) occurs in 56-98% of patients. [7, 8, 9]
  • Flank pain occurs in 30% of patients.
  • Upper urinary tract TCCs are an incidental finding in 15% of (asymptomatic) patients.
  • Symptoms of advanced disease are abdominal mass, anorexia, weight loss, and bone pain.

Robot-assisted laparoscopic nephroureterectomy is a relatively new procedure with promising early results. Similar to traditional laparoscopy, it is a minimally invasive surgery that minimizes surgical morbidity for the patient. However, unlike traditional laparoscopy, it simplifies excision of the distal ureter and bladder, and as such it has the potential for a more widespread adoption by urologists.

Short-term oncologic outcomes have been encouraging, and it seems reasonable to expect long-term outcomes as good as those seen with traditional laparoscopy, which in turn has been comparable to the outcomes of open surgery— the criterion standard for the treatment of upper tract TCC. Whether robotic assistance can improve the performance of lymphadenectomy, which is an essential component of this surgery, remains to be seen. Although challenging, large randomized trials with long-term follow-up comparing the outcomesofopenand robotic nephroureterectomies would be ideal.


Nephroureterectomy is considered the criterion standard for the treatment of large, high-grade, and invasive tumors of the renal pelvis or proximal ureter. It is also indicated for large, multifocal, or rapidly recurring, low-medium grade, noninvansive tumors of the renal pelvis or proximal ureter. [10, 11, 12, 13]

Because of the multifocal nature of these tumors and the consequent high risk of ipsilateral recurrence after partial resection, the kidney and the entire ureter, including the intramural portion and the ureteric orifice, should be removed. The risk of tumor recurrence in the remaining ureteral stump is in the range of 33-75%. [11, 14, 15]


Technical Considerations


This is a key component of nephroureterectomy, whether by open or laparoscopic (purely laparoscopic or hand- or robot-assisted) approach. Additionally, surgery may be performed extraperitoneally or transperitoneally, depending upon patient comorbidities, previous abdominal surgeries, and surgeon and patient preferences.

Distal Ureter and Bladder Cuff

During nephroureterectomy, standard practice is to remove the entire ipsilateral ureter, including the intramural portion and a 1 cm portion of the surrounding bladder (bladder cuff). Ideally, this should be achieved by en bloc, closed-system removal of the specimen without any spillage. Although the open technique has traditionally served as the criterion standard, it is associated with considerable morbidity. Therefore, several less-invasive techniques have evolved to minimize morbidity while attempting to conform to standard oncologic principles.

In 2011, Phe et al reviewed the various surgical techniques for excision of the distal ureter. [16] They reported that open removal of the distal ureter can be performed extravesically or intravesically with approximately 30% risk of bladder recurrence. The laparoscopic stapling technique maintains a closed system but runs the risk of incomplete excision and potential for stone formation on the staple line in the bladder wall. While transvesical laparoscopic detachment and ligation was oncologically sound, it was found to be technically difficult. The transurethral resection of ureteric orifice (TURUO) or the “pluck” technique is relatively easy to learn but carries the risks of tumor spillage, incomplete resection and need for repositioning the patient.

The technique of ureteric intussusception/stripping carries the risk of tumor spillage. The authors noted that the recurrence rates within the bladder after various management techniques of the distal ureter during nephroureterectomyvaried considerably, from 6.7% to 50%. Unfortunately, to date, no prospective randomized trials have compared the different approaches.


Komatsu et al reported that lymphadenectomy may be useful in determining the accurate stage of upper tract TCC but does not improve prognosis. [17] On the contrary, Miyake et al reported a survival benefit with lymphadenectomy for aggressive disease. [18] Because of the conflicting reports in the literature on the benefit of lymph node dissection, and its clear benefit in lower tract TCC , [19, 20, 21, 22] this is a topic of intense debate in the management of upper tract TCC. To complicate matters further, a lack of understanding and agreement with regard to what should be considered as regional lymph nodes exists.

Kondo et al examined the primary site of nodal metastasis according to primary tumor location and described regional lymph nodes corresponding to various parts of the upper urinary tract. [23] In tumors of the right renal pelvis, the primary metastatic sites were the right renal hilar, paracaval, and retrocaval nodes. Tumors of the upper two-thirds oftherightureter metastasized to inter-aortocaval nodes, in addition to the right renal hilar, paracaval, and retrocaval nodes. Tumors within the left renal pelvis or proximal ureter tended to metastasize to the left renal hilar and para-aortic nodes. Tumors of the lower ureter (on either the right or left) primarily metastasized inferior to the aortic bifurcation.

In a subsequent article, these authors observed that the extent of lymphadenectomy significantly influenced survival in patients with T3 or higher upper tract TCC. [24]

Evolution of Minimally Invasive Nephroureterectomy

Laparoscopic nephroureterectomy was first reported in the literature by Clayman and coworkers in 1991. [25] Since then, several centers of excellence have adopted the laparoscopic approach. Management of distal ureter including excision of the bladder cuff presents a significant challenge laparoscopically. Multiple techniques have been described to manage the distal ureter, none clearly superior to others. [26, 27, 28, 29, 30, 31] The challenge has been development of a technique that is safe, easily reproducible, and oncologically sound.

Robot-assisted nephroureterectomy was first reported by Rose et al in 2006. [32] In the 2 cases that they reported, the robot was used for only the nephrectomy portion of the surgery, and open incision was performed for excision of the distal ureter.

Later in the same year, Nanigian et al reported their series of 10 consecutive patients who underwent laparoscopic nephrectomy followed by robot-assisted transvesical excision of the distal ureter and bladder cuff. [33] In their technique, patients were initially placed in the modified flank position for laparoscopic nephrectomy. This was followed by robot-assisted distal ureterectomy for which one additional trocar was placed on the contralateral lower quadrant and the patient was switched to a steep Trendelenburg position. The robot was docked, the bladder was clam-shelled, and a cuff of bladder was removed en bloc with the specimen.

With the robot assistance, the ureteric orifice defect and bladder wall were closed in 2 layers.This technique was a good adaptation of the open technique of bladder cuff excision; however, concerns exist regarding the spillage of bladder contents when the bladder is bivalved in a patient who is in steep Trendelenburg. At 6-month follow-up, 9 out of 10 patients were tumor-free, while one had a remote recurrence at the bladder neck.

In 2008, Hu et al reported their technique of robot-assisted nephroureterectomy in which the robot was utilized in an extravesical excision of distal ureter and bladder cuff in 9 consecutive patients. [34] The first 5 patients were repositioned after laparoscopic nephrectomy from flank to lithotomy position to dock the robot between the legs for excision of the bladder cuff.

In the last 4 patients, the authors modified their approach and kept patients in the flank position throughout the entire procedure, with the robot docked in flank position at an angle of 30° to the foot of the table. This not only shortened operative time by obviating the need to reposition but also improved exposure by allowing gravity to displace bowel away from the distal ureter. With their extravesical approach, as opposed to a transvesical approach, the authors hoped to decrease the risk of tumor spillage, obviate the need for drain, shorten the duration of bladder catheterization,andminimizehematuria postoperatively.

To minimize operative time lost to repositioning and re docking of the robot, Park et al described their technique of “hybrid” port placement and “telescoping” the 8-mm robotic ports into 12-mm laparoscopic ports. [35] The first 6 patients were repositioned after the robotic nephrectomy, from flank to lithotomy position, and the robot was re docked for excision of the distal ureter and bladder cuff. The next 5 patients underwent the entire surgery without repositioning or re docking, which led to the reduction of operative time by approximately 50 minutes.

More recently, Hemal et al described their technique of a rather seamless transition from upper tract to lower tract surgery without the need to reposition the patient, re dock the robot, or “telescope” a robotic port into a 12-mm laparoscopic port. [36] Ports were strategically placed to allow access to the kidney, ureter, and bladder. The bladder cuff was excised extravesically, and the cystotomy was closed in 2 layers in the standard fashion. The authors reported that the “short-term” oncological outcomes revealed no recurrence in their series of 15 patients.



Despite the documented benefits of minimally invasive nephroureterectomy in perioperative morbidity and recovery, the oncological equivalence of this procedure to open nephroureterectomy remains to be established. The bar is set high for this procedure because upper tract TCC is a biologically aggressive disease with a high potential for recurrence and disease progression. For it to be recommended as an alternative to open surgery in formal guidelines, its noninferiority to the open approach in terms of oncological outcomes has to be proven.

Aboumohamed et al conducted intermediate-term follow-up for the use of robot-assisted laparoscopic nephroureterectomy with bladder cuff excision for the treatment of upper tract urothelial carcinoma, with the investigators reporting that the procedure offered satisfactory oncological control. Overall survival at 2 and 5 years was 86.9% and 62.6%, respectively, with cancer-specific survival being 92.9% and 69.5%, respectively, and recurrence-free survival being 65.3% and 57.1%, respectively. On multivariate analysis, an association was found between lymphovascular invasion and reduced cancer-specific survival. [37]

Several potential risks exist with laparoscopic nephroureterectomy that might compromise the oncological efficacy of the procedure. Concerns exist that tumor manipulation during laparoscopic nephroureterectomy may lead to increased gravitational migration of tumor cells and implantation into the bladder leading to future recurrence. Up to 50% of patients with primary upper tract TCC are at risk of secondary bladder recurrence due to tumor seeding. [38]

In addition, the high-pressure pneumoperitoneum required for laparoscopic surgeries could allow tumor cells to spread through pressurized aerosolization. [39] Furthermore, port site recurrence has also been reported in conjunction with laparoscopic nephroureterectomy. [40] These risks are controversial and need to be tested in clinical studies.

Within the last decade, several larg- scale retrospective studies and one prospective randomized trial have been published comparing the oncological outcome of laparoscopic and open nephroureterectomy. In one of the first large multi-institutional series, Manabe et al compared outcomes of 58 patients who underwent laparoscopic nephroureterectomy to 166 patients who underwent an open procedure. [41] At median follow-up of 13.6 months for the laparoscopic group and 28 months for the open group, they found no difference in the frequency of bladder recurrence, local recurrence, and distant metastases.

Two-year disease free survival rates were similar: 75.6% in the laparoscopic group versus 81.7% in the open. One incidence of port-site metastasis occurred in the laparoscopic group. The authors concluded that laparoscopic nephroureterectomy does not negatively affect long-term oncological control and can be considered an alternative modality.

In a large multi-institutional study with 1249 patients and a median follow-up of 49 months, Capitanio et al compared the outcomes for open and laparoscopic nephroureterectomy. [42] On univariate analysis they found recurrence rates and cancer-specific mortality rates were lower in the laparoscopic group; however, this was explained by selection bias, wherein patients with favorable pathologic stage and less lymphovascular invasion were selected for laparoscopic surgery.

After adjustment for these covariates, no difference was found between the groups in terms of recurrence and mortality. Absence of data on local recurrence in the bladder and the fact that a large proportion of patients (50% in laparoscopic group and 58% in open group) did not undergo bladder cuff excision were the major criticisms of this study. The authors failed to report the rates of port-site metastasis.

In another single-center study with 140 patients, Greco et al did not find any difference in 5-year disease-free survival (DFS) between the laparoscopic and open groups. [43] The 5-year DFS was 75% in the laparoscopic group (100% for pTa, 88% for pT1, 78% for pT2, and 35% for pT3) versus 73% in the open group (100% for pTa, 89% for pT1, 75% for pT2, and 31% for pT3).

More recently, in a single-center study, Favaretto et al reported their experience with 324 consecutive patients. [44] At a median follow-up of 23 months, no significant difference in recurrence or disease-specific mortality existed between the open and laparoscopic groups. Of note, the surgical technique was consistent—92% had bladder cuff control by the open technique and most patients underwent lymphadenectomy.

To date, only one randomized prospective study has compared the outcomes of open and laparoscopic nephroureterectomy reported in the literature. [45] This study raised some suspicion regarding the efficacy of the laparoscopic approach in the treatment of locally advanced upper tract TCC. Eighty patients with non metastatic upper tract TCC without a prior history of TCC were randomized equally between the 2 treatment arms. As expected, mean blood loss and mean time to discharge were significantly lower in the laparoscopic group.

At a median follow-up of 44 months, bladder recurrence, metastasis-free survival (MFS), and cancer-specific survival (CSS) were not significantly different between the 2 groups. When matched for pT3 and high-grade tumors, MFS and CSS were significantly lower in the laparoscopic group. The authors concluded that the efficacy of the laparoscopic approach in advanced-stage disease remained to be proven. At the same time, they acknowledged their results to bepreliminarybecause of small sample size.

In line with the results of Simone et al, Terakawa et al found a slightly lower disease-specific survival rate in a laparoscopic group with grade-3 disease; however, on multivariate analysis, surgical approach was not an independent predictor of survival irrespective of tumor grade. [46] To counter this, in another large French multicenter collaborative study with 609 patients, the authors reported no difference in survival between the laparoscopic and open groups. [47] The median follow-up in this study was 27 months. More specifically, the cancer-specific survival and recurrence-free survival for cases with advanced disease (pT3/pT4) were similar between the 2 groups.

Most recently, Stewart et al reported long-term outcomes of open and laparoscopic nephroureterectomy in a comparative study with 62 patients. [48] After a median follow-up of 13.6 years, they found no significant difference between the 2 groups in terms of bladder recurrence, overall survival, progression-free survival, or cancer-specific survival. Probability of progression-free survival at 10 years was 79% for open nephroureterectomy and 76% for the laparoscopic group and was unchanged at 15 years.

Overall, in the last decade, numerous retrospective studies have demonstrated oncological equivalence for laparoscopic and open nephroureterectomies. It appears the laparoscopic approach is equally efficacious in cancer control in expert hands at large institutions, and certainly for lower grade/stage tumors.

Some concerns exist with regard to laparoscopy for high-grade/stage upper tract TCCs in smaller studies that have not been borne out in subsequent large-scale studies. In interpreting these data, one has to keep in mind the heterogeneity of disease pathology and surgical techniques, especially with regard to handling the distal ureter and performance of concomitant lymphadenectomy. The ultimate choice of the surgical approach depends upon careful patient selection and the surgeon’s comfort with their abilities to perform an oncologically safe operation via a given approach.