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Adult Urology

ncidence of Local Recurrence andort Site Metastasis After Laparoscopicadical Nephroureterectomy

ichael Muntener, Edward M. Schaeffer, Frederico R. Romero,atthew E. Nielsen, Mohamad E. Allaf, Fabio Augusto R. Brito, Christian P. Pavlovich,

ouis R. Kavoussi, and Thomas W. Jarrett

BJECTIVES To address the incidence of local recurrence and port site metastasis in patients who underwentlaparoscopic radical nephroureterectomy (RNU) for upper tract transitional cell carcinoma(TCC).

ETHODS Between August 1993 and February 2006 116 laparoscopic RNU were performed in 115 patientsat our institution. A traditional open excision, a laparoscopic stapler resection or a differentapproach was used for the management of the distal ureter in 76, 27, and 11 cases, respectively.Clinical follow-up as well as perioperative and pathologic data were retrospectively collected.

ESULTS Perioperative and pathologic data were available in all 116 cases. Clinical outcomes wereavailable in 107 patients with a mean follow-up of 30.5 months (range 1 to 148). Six patients(5.6%) had a local recurrence develop, including 1 patient with port site metastasis (0.9%) at anaverage of 5.7 months. In 2 of these patients, violation of the ipsilateral urinary tract was notedperioperatively.

ONCLUSIONS We report, in this large single-center series of laparoscopic RNU, a low incidence of localrecurrence. Our results confirm that a laparoscopic approach to upper tract TCC does not resultin a clinically significant increased risk of tumor spillage provided that principles of oncologic

surgery are followed. UROLOGY 70: 864–868, 2007. © 2007 Elsevier Inc.

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pen radical nephroureterectomy (RNU) hasbeen the standard of care for high-grade or high-stage transitional cell carcinoma (TCC) of the

pper urinary tract. The procedure, however, carries sig-ificant morbidity caused by the incisional trauma from aingle large incision or from multiple incisions. Laparo-copic techniques were introduced as a less invasive al-ernative by Clayman et al.1 in 1991 and have sinceecome a new standard of care at many centers of excel-ence.2–8 The laparoscopic approach has distinct advan-ages in terms of blood loss, postoperative pain, andecovery time6,9–11 and equivalent short- and intermedi-te-term oncologic efficacy.5,6,9,12 However, adoption ofhese techniques especially for high-grade TCC hasagged compared with other solid renal tumors.13 This ist least in part because of concerns about local tumorontrol, given the aggressive nature of upper tract TCC

rom the The James Buchanan Brady Urological Institute, The Johns Hopkins Medicalnstitutions, Baltimore, Maryland; The Department of Urology, North Shore-IJ Health System, Long Island, New York; and Department of Urology, The Georgeashington University Medical Center, Washington, DCReprint requests: Michael Muntener, M.D., James Buchanan Brady Urological

nstitute, The Johns Hopkins Hospital, 600 N. Wolfe Street, Marburg 1, Baltimore,

mD 21287-2101. E-mail: muntener@jhmi.eduSubmitted June 19, 2006; accepted (with revisions) July 3, 2007

64 © 2007 Elsevier Inc.All Rights Reserved

nd the relatively limited experience with the laparo-copic approach. In fact, the long-term risk of localecurrence of TCC after laparoscopic surgery has receivedimited attention in the published literature.4,7,10 Theim of this study was to assess the incidence of localecurrence and port site metastasis after laparoscopicNU at our institution.

ATIENTS AND METHODS

fter institutional review board approval was obtained, theedical records of all 115 patients who underwent laparoscopicNU for upper tract TCC at our institution between August993 and February 2006 were retrospectively reviewed. Oneatient underwent a second laparoscopic RNU 7 years after therst procedure because of recurrence of TCC in the contralat-ral upper tract. Demographic, perioperative, pathologic, andlinical follow-up information was collected from the charts.

Four surgeons were involved in the reported procedures. Ourechnique of laparoscopic RNU has been reported in an earlierublication.3 No formal lymphadenectomy was performed. Onhe basis of the surgeon’s preference, either an open approach orlaparoscopic stapler was used to resect the distal ureter in theast majority of the cases. Follow-up consisted of cystoscopyvery 3 to 12 months and computed tomography (CT) or

agnetic resonance imaging (MRI) every 6 to 12 months, or

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hen clinically indicated. In patients who were not monitoredt our institution, follow-up information was collected fromreating physicians or the patients themselves. Follow-up timeas calculated from the date of surgery to the date of the most

ecent documented examination or patient contact.Local recurrence was defined as retroperitoneal or pelvic

xtravesical disease detected on CT or MRI. Recurrent diseaseonfined to retroperitoneal or pelvic lymph nodes was notonsidered a local recurrence. Port site metastasis was defined asisease recurrence to the abdominal wall at 1 or more trocar orxtraction sites.

Statistical analysis was performed by using commerciallyvailable software. Categorical data were compared with the usef Fisher exact test or the chi-square test, where appropriate.ontinuous data were compared with the Mann-Whitney U

est. A value of P � 0.05 was considered statistically significant.ll analyses were 2-sided.

ESULTSemographic data were available for all 115 patients anderioperative information and final pathology resultsere available in all 116 cases. Patient characteristics anderioperative information are shown in Table 1.

urgical Techniquen 4 patients, laparoscopic RNU was combined withpen radical cystectomy and urinary diversion. In theseases, the laparoscopic nephrectomy and dissection of thereter were performed first. Dissection of the distal ureteras carried out during the open cystectomy and the

pecimen was extracted en bloc through the cystectomyncision. The management of the distal ureter was trans-esical or extravesical open excision with a bladder cuffn 72 cases. In 27 cases, the distal ureter was resected bysing the previously described laparoscopic stapling tech-ique3; in 6 cases a part of the distal ureter was left in situ

or various reasons, in 3 cases the resection was cysto-copically assisted, and in 2 cases the ureter was clippednd transected at the level of the bladder. No informa-ion on the management of the distal ureter was availableor 2 cases. Intraoperative complications occurred in 8atients and 2 of these complications led to open con-ersion of the procedure. Four of these were hemorrhagicomplications with 1 caused by a misfire of the laparo-copic stapler at the level of the renal vein. The remain-ng complications included 1 bowel injury, 1 splenicaceration, 1 diaphragmatic injury, and 1 obturator nervenjury.

Pathologic outcomes are summarized in Table 2. In 7ases of low-grade disease, predominantly during thearly experience, the specimen was morcellated in aonpermeable laparoscopic retrieval bag (Cook Urolog-

cal Inc, Spencer, Indiana) before extraction, accountingor the incomplete pathology data. In 3 cases with TCCn preoperative biopsy, no malignant tumor (pT0) wasetected in the final pathologic specimen. In 2 of theseases, a high-grade TCC had been confirmed in the

reoperative biopsy. These were reviewed postoperatively i

ROLOGY 70 (5), 2007

o confirm the initial diagnosis. The third case involved4-cm lesion in the renal pelvis that was identified as

ow-grade TCC on biopsy. Final pathology in this caseas “papillary urothelial neoplasm of low malignant po-

ential.” These 3 cases were categorized as stage T0 andrade G0.

Follow-up information was available for 107 patientsith a mean follow-up of 30.5 months (range 1 to 148).uring this time, 6 patients (5.6%) had a local recur-

ence develop, including 3 patients with a retroperitonealecurrence, 2 patients with a pelvic recurrence, and 1atient with port site metastasis. In 2 of these patients,lear violation of the urinary tract was noted. The re-pective circumstances have been reported in previousublications.3,14 Briefly, 1 patient was initially misdiag-osed as having a ureteropelvic junction obstruction andnderwent an uncomplicated pyeloplasty. Final pathol-gy showed high grade TCC and the patient returned for

Table 1. Patient characteristics and perioperative infor-mation (n �116).

Median age (y) (range) 67 (34–90)Sex* (%)

Male 80 (69.6)Female 35 (30.4)

Median BMI (range) 27.3 (18.4–48.3)Tumor side (%)

Right 53 (45.7)Left 63 (54.3)

Tumor site† (%)Pelvicalyceal 89 (76.7)Proximal and mid ureter 20 (17.2)Distal ureter 26 (22.4)

History of bladder TCC (%)No 70 (60.3)Yes 46 (39.7)

Median operating time(min) (range)

286 (132–715)

Median estimated bloodloss (mL) (range)

200 (20–2200)

Intraoperativecomplications

108 No (93.1)

8 Yes (6.9)Conversion (%) 107 No (92.2)

8 to open surgery (6.9)1 to hand assisted (0.9

Median length of hospitalstay (d) (range)

4 (2–46)

Morcellation of thespecimen (%)

7 cases (6)

Lapbag used to extractspecimen (%)

79 No (68.1)

(Information unavailablein 2 cases)

35 Yes (30.2)

Management of the distalureter (%)

Laparoscopic staplerresection 27 (23.3)

(Information unavailablein 2 cases)

Open resection 76(65.5) Other 11 (9.5)

Other 11 (9.5)

BMI � Body mass index.* n � 115, 1 patient had 2 laparoscopic RNU.† In 3 patients (2.6%) no residual tumor was found and 22patients (19.0%) had pelvicalyceal and ureteral tumors.

psilateral laparoscopic nephroureterectomy. The patient

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ubsequently had an extensive retroperitoneal local re-urrence develop 7 months after the RNU. In the otheratient a double-J stent was inserted 1 week before thecheduled RNU. During the laparoscopic RNU, it wasoted that the stent had perforated the tumor-bearingenal pelvis with frank leakage into the retroperitoneum.his patient had metastasis develop at all 3 port sites 12onths after surgery.Detailed information on the 6 patients with local

ecurrence and port site metastasis is shown in Table 3.ecurrence was diagnosed at a mean (range) of 5.7 (1 to2) months after surgery. Three of these patients died ofCC at a mean time of 20.3 months (range 14 to 24)fter RNU and 3 patients were alive with disease 8, 18,nd 20 months after surgery, respectively.

On statistical analysis the only significant differencee found between patients who had a local recurrence orort site metastasis and patients who did not was in thereatment of the distal ureter. In the group with recur-ence more patients underwent a laparoscopic stapleresection than in the nonrecurrence group. Apart fromhis finding no significant differences were detected be-ween the 2 groups. The respective P-values are listed in

Table 2. Final pathology information (n � 116)

Median tumor size (cm) (range) 3.5 (0.5–10.5)Tumor stage (%)

T0 3 (2.6)Tis 9 (7.7)Ta 35 (30.2)T1 17 (14.7)T2 16 (13.8)T3 27 (23.3)T4 5 (4.3)Unavailable 4 (3.4)

Tumor grade (%)No malignancy 3 (2.6)Low grade 24 (20.7)High grade 89 (76.7)

Lymphnodes (%)N0 or Nx 108 (93.1)N� 8 (6.9)

Venous/lymphatic invasion (%)Not present 84 (72.4)Present 17 (14.7)Unavailable 15 (12.9)

CIS present (%)No 64 (55.2)Yes 46 (39.7)Unavailable 6 (5.1)

Multifocal disease (%)No 42 (36.2)Yes 65 (56.0)Unavailable 9 (7.8)

Surgical margins (%)Negative for tumor 93 (80.2)Positive for tumor 16 (13.8)Unavailable 7 (6)

Positive margin type (n � 16)Bladder cuff margin 13 (10 CIS)Soft tissue and vascular margin 3

able 3. Not shown in Table 3 is the comparison of the s

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groups with regard to bladder TCC history (P � 0.32)s well as tumor site (P � 0.31). Tumor characteristics ofatients who underwent laparoscopic stapler resection ofhe distal ureter did not differ from those of patients whonderwent open resection.

OMMENThe benefits of laparoscopic surgery with regard to peri-perative morbidity, cosmesis, and convalescence haveeen well established. Appropriate concerns surroundingncologic efficacy, however, have somewhat limited theirniversal use for malignant disease. Thus, urologists haveeen less likely to choose laparoscopic surgery for aggres-ive upper tract TCC than for other renal tumors.13 Thiss based in part on reports of a higher incidence of port

Table 3. Intraoperative and pathologic findings in patientswith local recurrence and port site metastasis*

ParameterNumber of cases

(n � 6) P

Morcellation of thespecimen

0 0.70

Lapbag usedNo 3 0.18Yes 3*

Management of the distalureter

Laparoscopic staplerresection

4* �0.05

Open resection 2Median tumor size (cm)

(range)4.3 (3.2–5.5) 0.59

Tumor stageTis 0Ta 0T1 2* 0.20T2 1T3 2T4 1

Tumor gradeLow grade 0 0.22High grade 6

Venous/lymphatic invasionNot present 1 0.06Present 2Information unavailable 3*

CIS presentNo 3 0.31Yes 3*

Multifocal diseaseNo 2* 0.35Yes 3Information unavailable 1

Surgical marginsNegative for tumor 5* 0.41Positive for tumor 1

Positive margin typeBladder cuff margin 1 (CIS) n/aSoft tissue and vascular

margin0

P-values represent the results from the statistical comparisonwith the patients who did not have local recurrence develop.

ite metastasis in the setting of TCC than has been

UROLOGY 70 (5), 2007

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eported for other urologic tumors.15 To our knowledge,cases of port site metastasis after laparoscopic RNU

ave been reported,16,17 including the case we describe inhis study. In 1 of these cases, like in 1 of our localecurrence patients TCC was not initially suspected.18

Local recurrence is an additional theoretical concernn this setting given the reports of port site metastases.ncreasing experience with laparoscopic RNU, however,as suggested that, overall, port site metastasis and localecurrence are rare phenomena.17,19 Nevertheless, therue incidence of these conditions is difficult to accu-ately ascertain because of the limited number of largeeries that have been published and the possibility ofnderreporting.15 Several contemporary authors haveuggested that, provided the principles of oncologic sur-ery are followed, incidences of both local recurrence andort site metastasis in upper tract TCC are more a func-ion of tumor biology than of surgical approach.19–21

We report, in this large single-center series of laparo-copic RNU, a 5.6% incidence of local recurrence, whichncludes a 0.9% incidence of port site metastasis. Givenhat the majority of our patients had high-grade, high-tage, and large-volume disease, these data compare fa-orably with the results reported in series of openephroureterectomy for upper tract TCC. In a review of8 studies, Rassweiler et al.17 found incidences of localecurrence of 0% to 15% both after open and afteraparoscopic RNU. In another multicenter series locore-ional recurrences were reported in 16 of 73 patients22%) after open nephroureterectomy.22 Very recentlyattori et al.23 reported local recurrence rates of 10%,

1%, and 6% for open, combined, and pure laparoscopicephroureterectomy, respectively. Also, incisional scaretastasis is a well-recognized problem in open oncologic

urgery with reported incidences of 0.4% for renal cellarcinoma and 1.5% for colon cancer.21 Some previouslyublished nephroureterectomy series included retroperi-oneal lymph node recurrences in their definition of localecurrence.23,24 If we expanded our definition accord-ngly, adding 3 patients, the local recurrence incidenceor our series would increase to 8.4%, still well within theange of previous reports.

Relative limitations of our study include its retrospec-ive nature and the intermediate term overall follow-up.evertheless, the natural history of upper tract TCC is

airly aggressive, with typically short median times todverse outcomes reported in most series.4,22 Our expe-ience is consistent with this, with the average time toetection of local recurrence (5.7 months) being substan-ially shorter than the mean follow-up time for the cohort30.5 months). Therefore, we feel confident that we haveot missed a significant number of patients with localecurrence because of inadequate follow-up.

Statistical analyses did not reveal significant associa-ions between specific patient characteristics and/orathologic findings among the patients who had local

ecurrence develop. This is likely attributable in part to c

ROLOGY 70 (5), 2007

he overall high prevalence of adverse tumor features inhe series as well as to the relatively small number ofatients who had recurrence. These findings are consis-ent with a recent report from Bariol et al.,12 which alsoid not find a statistically significant correlation betweenpper tract TCC stage and grade and the incidence ofocal recurrence. Nevertheless, all our patients with re-urrence had high-grade, invasive disease, and the per-entage with venous/lymphatic invasion was higher thann patients who did not recur. These findings are consis-ent with the common sense notion that aggressive tumorharacteristics represent a risk for local TCC recur-ence.7,15,20,21 The percentage of patients in whom aaparoscopic stapler resection was performed was highern the group that recurred (66%) than in the group thatid not (21%). This finding was statistically significantnd it adds to the concern others have already expressedgainst this surgical approach to the distal ureter.4 In oureries most of the operations were performed by veryxperienced laparoscopic surgeons. The patients whoater had a local recurrence develop were treated atarious stages of the respective surgeons’ experience. Thencidence of local recurrence therefore does not seem toe related to the learning curve associated with laparo-copic RNU.

Specific measures suggested to prevent recurrences af-er laparoscopic oncologic surgery include (1) minimalumor handling and strict avoidance of tumor boundaryiolation, (2) avoidance of morcellation, (3) use of anmpermeable bag for intact specimen retrieval, (4) trocarxation to avoid gas leakage alongside the trocar, and (5)voidance of laparoscopic surgery in the presence ofscites.15,17,21 The validity of time-honored principles ofncologic surgery is underscored by the fact that 2 of ourases with local recurrence were associated with obviousiolations of the tumor boundaries.Interestingly, no correlation between the use of a spec-

men retrieval bag and local recurrence was found. Inact, the percentage of patients in whom a bag was usedas even higher in the group that recurred. In the ma-

ority of our patients an open transvesical or extravesicalpproach was chosen to resect the distal ureter undypically the intact specimen was extracted en blochrough this incision. Our findings of fewer local recur-ences in patients in whom open surgery was used toesect the distal ureter with bladder cuff suggest that thisay be the most prudent manner of handling the distal

reter and that a laparoscopic stapler resection of theladder cuff is an inferior method from an oncologictandpoint. Similarly, our results suggest that under theseircumstances the use of a specimen retrieval bag is notn effective means to prevent local tumor recurrence.

ONCLUSIONSn this large, single-center series of laparoscopic RNU, weeport a 5.6% incidence of local recurrence, which in-

ludes a 0.9% incidence of port site metastasis. The

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pecific circumstances of 2 patients with local recurrencenderscore the necessity of following strict oncologicurgical principles, regardless of the technique used in theanagement of this highly virulent disease. These find-

ngs are well within the range of published reports frompen surgery and therefore confirm that a laparoscopicpproach to upper tract TCC does not, in and of itself,ubstantially increase the risk of tumor spillage.

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