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Comparative Study of Oncologic Outcome of Laparoscopic Nephroureterectomy and Standard Nephroureterectomy for Upper Urinary Tract Transitional Cell Carcinoma
Adult Urology Comparative Study of Oncologic Outcome of Laparoscopic Nephroureterectomy and Standard Nephroureterectomy for Upper Urinary Tract Transitional Cell Carcinoma Daisuke Manabe, Takashi Saika, Shin Ebara, Shinya Uehara, Atsushi Nagai, Ryuji Fujita, Shin Irie, Daisuke Yamada, Tomoyasu Tsushima, Yasutomo Nasu, and Hiromi Kumon, for the Okayama Urological Research Group, Okayama, Japan OBJECTIVES
METHODS
RESULTS
CONCLUSIONS
To determine the oncologic safety of laparoscopic nephroureterectomy (LNU), we compared the long-term oncologic outcome of LNU versus open nephroureterectomy (ONU) in patients with upper tract transitional cell carcinoma. A total of 367 nephroureterectomy procedures were performed at our institutes for upper tract transitional cell carcinoma without distant metastases. Of 224 patients without concomitant or previous bladder cancer, 58 underwent LNU with open intact specimen retrieval plus open distal ureter and bladder cuff removal and 166 underwent ONU. Their data were reviewed and analyzed retrospectively. The mean follow-up was 13.6 months (range 14 to 34) for the LNU group and 28.0 months (range 14 to 36) for the ONU group. Bladder recurrence was recognized in 19 patients (32.8%) after LNU at a median follow-up of 5.6 months compared with 63 patients (38.0%) after ONU. Local recurrence only developed in 2 patients (1.1%) after ONU. One port site metastasis occurred in a patient who had undergone LNU. Distant metastases developed in 10 patients (17.2 %) after LNU and 33 patients (19.9%) after ONU. The frequency of bladder recurrence, local recurrence, and distant metastases did not differ significantly between the two groups. The actual disease-free 2-year survival rates were similar (75.6% versus 81.7%). In all patients, the risk of metastases and death increased with advanced tumor stage and grade, but not by surgical procedure. In the surgical management of upper tract transitional cell carcinoma, LNU does not negatively affect long-term oncologic control and can be considered an alternative modality. Tumor stage and grade are, however, important prognostic factors in the incidence of metastases and cancer-specific mortality. UROLOGY 69: 457– 461, 2007. © 2007 Elsevier Inc.
O
pen nephroureterectomy (ONU) with bladder cuff excision has been considered the reference standard for treatment of upper urinary tract transitional cell carcinoma (TCC) during the past decades. However, the morbidity of open surgery (eg, severe pain and lengthy hospital stay) is inevitable. In 1991, Clayman et al.1 first described the technique of laparoscopic nephroureterectomy (LNU), which was soon replicated by various investigators worldwide.2,3 Recently, From the Department of Urology, Okayama University Medical School, Okayama; Department of Urology, Kure Kyosai Hospital, Kure; Department of Urology, Okayama Central Hospital, Okayama; Department of Urology, Mitoyo General Hospital, Kanonji; and Department of Urology, National Okayama Medical Center, Okayama, Japan Reprint requests: Takashi Saika, M.D., Ph.D., Department of Urology, Okayama University Medical School, 2-5-1 Shikata-cho Okayama, 700-8558 Japan. E-mail: [email protected] Submitted: June 12, 2006; accepted (with revisions): November 16, 2006
© 2007 Elsevier Inc. All Rights Reserved
LNU has been used to treat upper urinary tract TCC, with reduced morbidity. However, when considering the oncologic indications, such advantages must be balanced against the possible risks, such as port site metastases and local recurrence.4,5 With the increasing acceptance of laparoscopic radical nephrectomy for renal cell cancer, some institutes6 –15 have recently reported comparative studies on the oncologic aspects of ONU and LNU. However, these data come from a relatively small number of patients with short-term follow-up. Additionally, some of the reports included patients with previous or concomitant bladder cancer. To determine whether the oncologic safety of LNU is at least equivalent to that of ONU, the oncologic outcome of LNU versus ONU was compared in a multi-institute study of a relatively large number of patients with upper tract TCC and without previous or concomitant bladder cancer. 0090-4295/07/$32.00 doi:10.1016/j.urology.2006.11.005
457
Table 2. Oncologic results
Table 1. Patient characteristics Characteristic Age (yr) Mean Range Sex Male Female Side Left Right Location Ureter Pelvis Both Unknown Urine cytology Positive Negative Suspicious Unknown Morphology Papillary Nonpapillary Mixed Unknown No. Single Multiple Unknown Pathologic stage pTa pT1 pT2 pT3 pT4 pTis Grade 1 2 3
LNU (n ⫽ 58)
ONU (n ⫽ 166)
P Value
72 ⫾ 8.3 48–84
72 ⫾ 8.9 46–92
0.575
40 (69.0) 18 (31.0)
114 (68.7) 52 (31.3)
14 (24.1) 44 (75.9)
94 (56.6) 72 (43.4)
33 (56.9) 22 (37.9) 3 (5.2) 0 (0)
72 (43.4) 87 (52.4) 5 (3.0) 2 (1.2)
26 (44.8) 25 (43.1) 3 (5.2) 4 (6.9)
88 (53.0) 50 (30.1) 10 (6.0) 18 (10.9)
38 (65.5) 18 (31.0) 2 (3.5) 0 (0)
116 (69.9) 43 (25.9) 1 (0.6) 6 (3.6)
42 (72.4) 14 (24.1) 2 (3.5)
123 (74.1) 39 (23.5) 4 (2.4)
11 (19.0) 16 (27.6) 6 (10.3) 24 (41.4) 0 (0) 1 (1.7)
22 (13.3) 41 (24.7) 16 (9.6) 73 (44.0) 7 (4.2) 7 (4.2)
4 (6.9) 31 (53.4) 23 (39.7)
15 (9.0) 87 (52.4) 64 (38.6)
0.967 ⬍0.05 0.188
0.230
0.906
0.497
0.880
ONU
⫽
open
MATERIAL AND METHODS We retrospectively reviewed 367 patients with upper urinary tract TCC from January 2000 to December 2004. Of 224 patients without concomitant or previous bladder cancer, 58 (40 men and 18 women) with a mean age of 72 years (range 48 to 84) underwent LNU with open intact specimen retrieval plus open distal ureter and bladder cuff removal, and 166 (114 men and 52 women) with a mean age of 72 years (range 46 to 92) underwent ONU with bladder cuff excision. Upper urinary tract TCC was diagnosed by intravenous urography, retrograde pyelography, computed tomography of the abdomen, magnetic resonance imaging, and ureteroscopy with or without biopsy. In all patients, preoperative cystoscopy and radiologic examinations were performed to rule out metastasis and concomitant bladder tumors. Pertinent patient characteristics are given in Table 1. The male/female ratio, distribution of the site of upper tract TCC, urine cytology, tumor morphology, and pathologic feature were similar between the two groups. Only the distribution of the side was statistically different. 458
LNU (n ⫽ 58)
ONU (n ⫽ 166)
P Value
Bladder recurrence 19 (32.8) 63 (38.0) 0.480 Median interval to 5.6 ⫾ 7.0 6.4 ⫾ 10.6 recurrence (mo) Metastasis 10 (17.2) 33 (19.9) 0.660 Median interval to 14.1 ⫾ 8.8 11.2 ⫾ 13.3 metastasis (mo) Disease-free 2-year 75.6 81.7 survival rate (%) Local recurrence (n) 1 (port) 2 Survival duration (%) Cause-specific 85.2 87.0 2-yr survival rate Overall 2-yr 83.7 83.6 survival rate Abbreviations as in Table 1. Data in parentheses are percentages.
0.156
LNU ⫽ laparoscopic nephroureterectomy; nephrourecterectomy. Data in parentheses are percentages.
Variable
LNU was performed using the retroperitoneal approach. The patients were placed in a lateral position. After a retroperitoneal working space had been created using a balloon dissector, the pneumoretroperitoneum was maintained with carbon dioxide gas at 8 mm Hg. Four trocars were inserted in the usual manner. The posterior peritoneum was mobilized medially so that dissection of Gerota’s fascia and the renal pedicle could be fully performed. The lymphatic channels around the renal pedicle were excised to expose the renal artery, which was isolated, clipped, and divided. The renal vein was also mobilized and secured with a vascular stapler or clips. Next, the ureter was secured with clips. Caudally, the fatty tissue around the ureter was divided to the cross with the iliac vessels. Lymphadenectomy was not performed routinely for renal pelvic cancer. After the patient had been rotated back to the horizontal position, an approximately 7-cm pararectal incision or mid-lower abdominal incision was made, and the entire distal ureter, including the intramural portion and the ureteral orifice, was removed. This was performed in two ways. In the case of pelvic or upper ureter cancer, the dissection was performed by extravesical dissection of the distal ureter and the intramural portion within the bladder wall all the way to the ureteral orifice. The ureter was tented up, and the bladder mucosa was divided between clamps. In the case of lower ureter cancer, an anterior cystostomy was made and intravesical and extravesical dissection performed. One centimeter of bladder mucosa was included circumferentially around the ureteral orifice. The entire nephroureterectomy specimen was removed en bloc using the incision. On the basis of these surgical procedures and the histopathologic findings, completely removal of the distal ureter was confirmed. Cystoscopy was performed every 3 months for 2 years after transurethral resection, then every 4 months from 2 to 3 years, every 6 months from 3 to 5 years, and annually after 5 years. Urine cytology was examined at cystoscopy. Intravenous urography, pelvic computed tomography, and chest radiography were performed annually. The mean follow-up was 13.6 months (range 14 to 34) for the LNU group and 28.0 months (range 14 to 36) for the ONU group. The oncologic parameters (local recurrence, bladder tumor, distant metastasis, survival) were recorded and compared beUROLOGY 69 (3), 2007
Figure 1. (A) Intravesicle recurrences, (B) progression-free survival, (C) cause-specific survival, and (D) overall survival according to surgical procedures. No statistically significant difference was recognized between LNU and ONU groups for any of these variables. tween the two groups using the Mann-Whitney U test. Diseasespecific survival was calculated from the date of surgery to the date of the last follow-up visit and was analyzed using the Kaplan-Meier method. For all statistical tests, P ⬍0.05 was considered to indicate a significant difference.
RESULTS Table 2 gives the comparative oncologic results between the LNU and ONU groups. Bladder tumor recurrence occurred in 19 patients (32.8%) in the LNU group and 63 patients (38.0%) in the ONU group. No statistically significant difference was observed (P ⫽ 0.480). The median duration to the intravesical recurrences was 5.6 months and 6.4 months in the LNU and ONU groups, respectively. No statistically significant difference was found between the two groups (P ⫽ 0.911; Fig 1A). Local recurrence developed in 1 patient at the port site in the LNU group and in 2 patients in the ONU group. In the case of port site recurrence, urine extravasation resulting from urinary tract obstruction by ureteral cancer was observed before surgery. Distant metastasis developed in 10 patients (17.2%) in the LNU group and 33 patients (19.9%) in the ONU group. The median duration to distant metastasis recurrence was 14.1 months and 11.2 months in the LNU and ONU groups, respectively. No statistically significant difference was obUROLOGY 69 (3), 2007
served in progression-free survival rates (P ⫽ 0.594), and the actual disease-free 2-year survival rate was 75.6% and 81.7% in the LNU and ONU groups, respectively (Fig. 1B). Five patients in the LNU group died of distant metastasis (two in the lung, one in the liver, one in the liver and port site, and one in the lymph nodes) during the follow-up period. Twenty-five patients in the ONU group died of distant metastasis (eight in the bone, two in the lung, five in the liver, two in the local site, and three in the lymph nodes) during the follow-up period. No statistically significant difference was observed in the cause-specific survival (P ⫽ 0.889; Fig. 1C) or overall survival (P ⫽ 0.532; Fig. 1D) rate. For all patients, advanced tumor stage and grade increased the risk of metastases and death (Fig. 2).
COMMENT With recent technical improvements, the rate of complications with LNU has decreased. Several investigators have introduced laparoscopic procedures for radical nephroureterectomy and suggested their benefit for patient recovery with disease control comparable to that of traditional open surgery on the basis of the results of comparative studies (Table 3). However, the number of patients in each study has been relatively small. In addi459
Figure 2. (A) Progression-free survival and (B) overall survival according to stage. (C) Progression-free survival and (D) overall survival according to cancer grade. Statistically significant better survival was observed in patients with lower stage (P ⬍0.001) and in patients with lower grade (P ⬍0.01).
Table 3. Results of comparative studies between LNU and ONU for upper urinary tract TCC Investigator Shalhav et al.6 McNeill et al.7 Kawauchi et al.8 Klingler et al.9 Rassweiler et al.14 Bariol et al.11 Tsujihata et al.13 Present study
LNU/ONU (n)
Bladder Recurrence (%)
Local Recurrence (%)
Distant Metastasis (%)
2-yr Survival (%)
13/13 25/42 34/34 19/15 23/21 26/42 25/24 58/166
23/53.8 28/42 9/38 10.5/13.3 34.8/14.4 28/42 28/33.3 32.8/38.0
15.3/0 8/15.4 0/0 5.3/6.6 0/4.8 4/15 n.a. 2.0*/1.0
15.3/23 28/18 6.0/9.0 10.5/6.6 17.4/28.5 28/18 0/8 17.2/19.9
77/69 74/68 NA 94.7/93.7 89/63 NA NA 85.2/87.0
TCC ⫽ transitional cell carcinoma; NA ⫽ not available; other abbreviations as in Table 1. * Port site recurrence.
tion, the oncologic background (eg, history of, or concomitant, bladder tumor) and surgical procedure, especially in terms of distal ureterectomy, which could affect the oncologic outcome, have differed in those studies. Regarding the radical nephroureterectomy procedure, the disposal method of the distal ureter and bladder cuff is one point of controversy. A number of different approaches to the distal ureter have been described with varying degrees of oncologic safety. Although using minimally invasive techniques is commendable in an effort to decrease postoperative morbidity, we believe that establishing better oncologic outcomes is a more important issue. A number of cases of local recurrence have been described using the “pluck” technique. We have already 460
reported that nephroureterectomy with transurethral stripping has a significantly greater intravesical recurrence rate statistically than does conventional nephroureterectomy with a bladder cuff.16 Therefore, every patient in the present series underwent removal of the distal ureter with an open technique. The low rate of local recurrence in the present study has justified this policy. Our present study also had some problems because it was retrospective. First, we had no definitive criteria for choosing the surgical procedure, including the indication for lymphadenectomy, which might have caused the difference in the mean follow-up periods between the two groups. Second, the follow-up period in the LNU group UROLOGY 69 (3), 2007
might not have been long enough to evaluate the survival. However, our study does bring some precious information regarding the oncologic outcome after surgery of upper urinary tract TCC, including the following. Our series did not include patients with a history of, or concomitant, bladder tumor. The LNU and ONU groups were equivalent with respect to the grade and stage of the tumor removed, which could affect bladder recurrence, development of metastases, and survival. Our study is unique in this point of comparison with previous reports. With this similar background, the incidence of metastases and bladder recurrence were within the expected range17 and were equal in the LNU and ONU groups. Predictors of bladder recurrence could not be identified. The survival data have confirmed that the clinical progression reflected the aggressive nature of the initial disease and not the surgical procedure, although the follow-up period for LNU might be relatively short to draw such a conclusion. Advanced stage and grade have been confirmed as predictors of metastatic recurrence and death. Our results suggest that LNU with open ureterectomy seems to be a safe alternative for the treatment of upper urinary tract TCC with cancer control similar to that of ONU. One patient experienced a port site recurrence. Rassweiler et al.5 reported 6 cases of port site metastasis (1.6%) in 377 patients, occurring 3 to 12 months after laparoscopy. Klingler et al.9 noted that the use of the ultrasonic shears for tissue dissection results in uncontrollable tissue and fluid evaporation that might be an origin of cancer cell spread. In our case, extravasated urine, which might have contained cancer cells, was present in the surgical field. This was one possible reason for local recurrence. In such a case, the use of ultrasonic shears might be avoided for scattering cancer cells during LNU.
CONCLUSIONS In the surgical management of upper tract TCC, LNU does not negatively affect oncologic control and can be an alternative modality. The tumor stage and grade are, however, important prognostic factors in the development of metastases and cancer-specific mortality. The results from longer term studies are warranted to clarify this issue.
UROLOGY 69 (3), 2007
References 1. Clayman RV, Kavoussi LR, Figenshau RS, et al: Laparoscopic nephroureterectomy: initial clinical case report. J Laparoendocopic Surg 1: 343–349, 1991. 2. Rassweiler JJ, Henkel TO, Potempa DM, et al: The technique of transperitoneal laparoscopic nephrectomy, adrenalectomy, and nephroureterectomy. Eur Urol 23: 425– 430, 1993. 3. Yoshino Y, Ono Y, Hattori R, et al: Retroperitoneoscopic nephroureterectomy for transitional cell carcinoma of the renal pelvis and ureter: Nagoya experience. Urology 61: 533–538, 2003. 4. Cicco A, Salomon L, Hoznek H, et al: Carcinological risks and retroperitoneal laparoscopy. Eur Urol 38: 606 – 612, 2000. 5. Rassweiler J, Tsivian A, Kumar AV, et al: Oncological safety of laparoscopic surgery for urological malignancies: experience with more than 1,000 operations. J Urol 169: 2072–2075, 2003. 6. Shalhav AL, Dunn MD, Portis AJ, et al: Laparoscopic nephroureterectomy for upper tract transitional cell cancer: the Washington University experience. J Urol 163: 1100 –1104, 2000. 7. McNeill SA, Chrisofos M, and Tolley DA: The long-term outcome after laparoscopic nephroureterectomy: a comparison with open nephroureterectomy. BJU Int 86: 619 – 623, 2000. 8. Kawauchi A, Fujiti A, Ukimura O, et al: Hand-assisted retroperitoneoscopic nephroureterectomy: comparison with the open procedure. J Urol 169: 890 – 894, 2003. 9. Klingler HC, Lodde M, Pycha A, et al: Modified laparoscopic nephroureterectomy for treatment of upper urinary tract transitional cell cancer is not associated with increased risk of tumor recurrence. Eur Urol 44: 442– 447, 2003. 10. Hattori R, Ono Y, Gotoh M, et al: Retroperitoneoscopic nephroureterectomy for transitional cell carcinoma of the renal pelvis and ureter: Nagoya experience. J Urol 169(suppl): 77, 2003. 11. Bariol SV, Stewart GD, McNeill SA, et al: Oncological control following laparoscopic nephroureterectomy: 7-year outcome. J Urol 172: 1805–1808, 2004. 12. Wolf JS Jr, Dash A, Hollenbeck BK, et al: Intermediate followup of hand assisted laparoscopic nephroureterectomy for urothelial carcinoma: factors associated with outcomes. J Urol 173: 1102–1107, 2005. 13. Tsujihata M, Nonomura N, Tsujimura A, et al: Laparoscopic nephroureterectomy for upper tract transitional cell carcinoma: comparison of laparoscopic and open surgery. Eur Urol 49: 332– 336, 2006. 14. Rassweiler JJ, Schulze M, Marrero R, et al: Laparoscopic nephroureterectomy for upper urinary tract transitional cell carcinoma: is it better than open surgery? Eur Urol 46: 690 – 697, 2004. 15. El Fettouh HA, Rassweiler JJ, Schulze M, et al: Laparoscopic radical nephroureterectomy: results of an international multicenter study. Eur Urol 42: 447– 452, 2002. 16. Saika T, Nishiguchi J, Tsushima T, et al: Comparative study of ureteral stripping versus open ureterectomy for nephroureterectomy in patients with transitional carcinoma of the renal pelvis. Urology 63: 848 – 852, 2004. 17. Sagalowsky AI, and Jarrett TW: Management of urothelial tumors of the renal pelvis and ureter, in Walsh PC, Retik AB, Vaughan ED, et al (Eds): Campbell’s Urology, 8th ed. Philadelphia, WB Saunders, 2002, vol 4, pp 2845–2847.
461
METHODS
RESULTS
CONCLUSIONS
To determine the oncologic safety of laparoscopic nephroureterectomy (LNU), we compared the long-term oncologic outcome of LNU versus open nephroureterectomy (ONU) in patients with upper tract transitional cell carcinoma. A total of 367 nephroureterectomy procedures were performed at our institutes for upper tract transitional cell carcinoma without distant metastases. Of 224 patients without concomitant or previous bladder cancer, 58 underwent LNU with open intact specimen retrieval plus open distal ureter and bladder cuff removal and 166 underwent ONU. Their data were reviewed and analyzed retrospectively. The mean follow-up was 13.6 months (range 14 to 34) for the LNU group and 28.0 months (range 14 to 36) for the ONU group. Bladder recurrence was recognized in 19 patients (32.8%) after LNU at a median follow-up of 5.6 months compared with 63 patients (38.0%) after ONU. Local recurrence only developed in 2 patients (1.1%) after ONU. One port site metastasis occurred in a patient who had undergone LNU. Distant metastases developed in 10 patients (17.2 %) after LNU and 33 patients (19.9%) after ONU. The frequency of bladder recurrence, local recurrence, and distant metastases did not differ significantly between the two groups. The actual disease-free 2-year survival rates were similar (75.6% versus 81.7%). In all patients, the risk of metastases and death increased with advanced tumor stage and grade, but not by surgical procedure. In the surgical management of upper tract transitional cell carcinoma, LNU does not negatively affect long-term oncologic control and can be considered an alternative modality. Tumor stage and grade are, however, important prognostic factors in the incidence of metastases and cancer-specific mortality. UROLOGY 69: 457– 461, 2007. © 2007 Elsevier Inc.
O
pen nephroureterectomy (ONU) with bladder cuff excision has been considered the reference standard for treatment of upper urinary tract transitional cell carcinoma (TCC) during the past decades. However, the morbidity of open surgery (eg, severe pain and lengthy hospital stay) is inevitable. In 1991, Clayman et al.1 first described the technique of laparoscopic nephroureterectomy (LNU), which was soon replicated by various investigators worldwide.2,3 Recently, From the Department of Urology, Okayama University Medical School, Okayama; Department of Urology, Kure Kyosai Hospital, Kure; Department of Urology, Okayama Central Hospital, Okayama; Department of Urology, Mitoyo General Hospital, Kanonji; and Department of Urology, National Okayama Medical Center, Okayama, Japan Reprint requests: Takashi Saika, M.D., Ph.D., Department of Urology, Okayama University Medical School, 2-5-1 Shikata-cho Okayama, 700-8558 Japan. E-mail: [email protected] Submitted: June 12, 2006; accepted (with revisions): November 16, 2006
© 2007 Elsevier Inc. All Rights Reserved
LNU has been used to treat upper urinary tract TCC, with reduced morbidity. However, when considering the oncologic indications, such advantages must be balanced against the possible risks, such as port site metastases and local recurrence.4,5 With the increasing acceptance of laparoscopic radical nephrectomy for renal cell cancer, some institutes6 –15 have recently reported comparative studies on the oncologic aspects of ONU and LNU. However, these data come from a relatively small number of patients with short-term follow-up. Additionally, some of the reports included patients with previous or concomitant bladder cancer. To determine whether the oncologic safety of LNU is at least equivalent to that of ONU, the oncologic outcome of LNU versus ONU was compared in a multi-institute study of a relatively large number of patients with upper tract TCC and without previous or concomitant bladder cancer. 0090-4295/07/$32.00 doi:10.1016/j.urology.2006.11.005
457
Table 2. Oncologic results
Table 1. Patient characteristics Characteristic Age (yr) Mean Range Sex Male Female Side Left Right Location Ureter Pelvis Both Unknown Urine cytology Positive Negative Suspicious Unknown Morphology Papillary Nonpapillary Mixed Unknown No. Single Multiple Unknown Pathologic stage pTa pT1 pT2 pT3 pT4 pTis Grade 1 2 3
LNU (n ⫽ 58)
ONU (n ⫽ 166)
P Value
72 ⫾ 8.3 48–84
72 ⫾ 8.9 46–92
0.575
40 (69.0) 18 (31.0)
114 (68.7) 52 (31.3)
14 (24.1) 44 (75.9)
94 (56.6) 72 (43.4)
33 (56.9) 22 (37.9) 3 (5.2) 0 (0)
72 (43.4) 87 (52.4) 5 (3.0) 2 (1.2)
26 (44.8) 25 (43.1) 3 (5.2) 4 (6.9)
88 (53.0) 50 (30.1) 10 (6.0) 18 (10.9)
38 (65.5) 18 (31.0) 2 (3.5) 0 (0)
116 (69.9) 43 (25.9) 1 (0.6) 6 (3.6)
42 (72.4) 14 (24.1) 2 (3.5)
123 (74.1) 39 (23.5) 4 (2.4)
11 (19.0) 16 (27.6) 6 (10.3) 24 (41.4) 0 (0) 1 (1.7)
22 (13.3) 41 (24.7) 16 (9.6) 73 (44.0) 7 (4.2) 7 (4.2)
4 (6.9) 31 (53.4) 23 (39.7)
15 (9.0) 87 (52.4) 64 (38.6)
0.967 ⬍0.05 0.188
0.230
0.906
0.497
0.880
ONU
⫽
open
MATERIAL AND METHODS We retrospectively reviewed 367 patients with upper urinary tract TCC from January 2000 to December 2004. Of 224 patients without concomitant or previous bladder cancer, 58 (40 men and 18 women) with a mean age of 72 years (range 48 to 84) underwent LNU with open intact specimen retrieval plus open distal ureter and bladder cuff removal, and 166 (114 men and 52 women) with a mean age of 72 years (range 46 to 92) underwent ONU with bladder cuff excision. Upper urinary tract TCC was diagnosed by intravenous urography, retrograde pyelography, computed tomography of the abdomen, magnetic resonance imaging, and ureteroscopy with or without biopsy. In all patients, preoperative cystoscopy and radiologic examinations were performed to rule out metastasis and concomitant bladder tumors. Pertinent patient characteristics are given in Table 1. The male/female ratio, distribution of the site of upper tract TCC, urine cytology, tumor morphology, and pathologic feature were similar between the two groups. Only the distribution of the side was statistically different. 458
LNU (n ⫽ 58)
ONU (n ⫽ 166)
P Value
Bladder recurrence 19 (32.8) 63 (38.0) 0.480 Median interval to 5.6 ⫾ 7.0 6.4 ⫾ 10.6 recurrence (mo) Metastasis 10 (17.2) 33 (19.9) 0.660 Median interval to 14.1 ⫾ 8.8 11.2 ⫾ 13.3 metastasis (mo) Disease-free 2-year 75.6 81.7 survival rate (%) Local recurrence (n) 1 (port) 2 Survival duration (%) Cause-specific 85.2 87.0 2-yr survival rate Overall 2-yr 83.7 83.6 survival rate Abbreviations as in Table 1. Data in parentheses are percentages.
0.156
LNU ⫽ laparoscopic nephroureterectomy; nephrourecterectomy. Data in parentheses are percentages.
Variable
LNU was performed using the retroperitoneal approach. The patients were placed in a lateral position. After a retroperitoneal working space had been created using a balloon dissector, the pneumoretroperitoneum was maintained with carbon dioxide gas at 8 mm Hg. Four trocars were inserted in the usual manner. The posterior peritoneum was mobilized medially so that dissection of Gerota’s fascia and the renal pedicle could be fully performed. The lymphatic channels around the renal pedicle were excised to expose the renal artery, which was isolated, clipped, and divided. The renal vein was also mobilized and secured with a vascular stapler or clips. Next, the ureter was secured with clips. Caudally, the fatty tissue around the ureter was divided to the cross with the iliac vessels. Lymphadenectomy was not performed routinely for renal pelvic cancer. After the patient had been rotated back to the horizontal position, an approximately 7-cm pararectal incision or mid-lower abdominal incision was made, and the entire distal ureter, including the intramural portion and the ureteral orifice, was removed. This was performed in two ways. In the case of pelvic or upper ureter cancer, the dissection was performed by extravesical dissection of the distal ureter and the intramural portion within the bladder wall all the way to the ureteral orifice. The ureter was tented up, and the bladder mucosa was divided between clamps. In the case of lower ureter cancer, an anterior cystostomy was made and intravesical and extravesical dissection performed. One centimeter of bladder mucosa was included circumferentially around the ureteral orifice. The entire nephroureterectomy specimen was removed en bloc using the incision. On the basis of these surgical procedures and the histopathologic findings, completely removal of the distal ureter was confirmed. Cystoscopy was performed every 3 months for 2 years after transurethral resection, then every 4 months from 2 to 3 years, every 6 months from 3 to 5 years, and annually after 5 years. Urine cytology was examined at cystoscopy. Intravenous urography, pelvic computed tomography, and chest radiography were performed annually. The mean follow-up was 13.6 months (range 14 to 34) for the LNU group and 28.0 months (range 14 to 36) for the ONU group. The oncologic parameters (local recurrence, bladder tumor, distant metastasis, survival) were recorded and compared beUROLOGY 69 (3), 2007
Figure 1. (A) Intravesicle recurrences, (B) progression-free survival, (C) cause-specific survival, and (D) overall survival according to surgical procedures. No statistically significant difference was recognized between LNU and ONU groups for any of these variables. tween the two groups using the Mann-Whitney U test. Diseasespecific survival was calculated from the date of surgery to the date of the last follow-up visit and was analyzed using the Kaplan-Meier method. For all statistical tests, P ⬍0.05 was considered to indicate a significant difference.
RESULTS Table 2 gives the comparative oncologic results between the LNU and ONU groups. Bladder tumor recurrence occurred in 19 patients (32.8%) in the LNU group and 63 patients (38.0%) in the ONU group. No statistically significant difference was observed (P ⫽ 0.480). The median duration to the intravesical recurrences was 5.6 months and 6.4 months in the LNU and ONU groups, respectively. No statistically significant difference was found between the two groups (P ⫽ 0.911; Fig 1A). Local recurrence developed in 1 patient at the port site in the LNU group and in 2 patients in the ONU group. In the case of port site recurrence, urine extravasation resulting from urinary tract obstruction by ureteral cancer was observed before surgery. Distant metastasis developed in 10 patients (17.2%) in the LNU group and 33 patients (19.9%) in the ONU group. The median duration to distant metastasis recurrence was 14.1 months and 11.2 months in the LNU and ONU groups, respectively. No statistically significant difference was obUROLOGY 69 (3), 2007
served in progression-free survival rates (P ⫽ 0.594), and the actual disease-free 2-year survival rate was 75.6% and 81.7% in the LNU and ONU groups, respectively (Fig. 1B). Five patients in the LNU group died of distant metastasis (two in the lung, one in the liver, one in the liver and port site, and one in the lymph nodes) during the follow-up period. Twenty-five patients in the ONU group died of distant metastasis (eight in the bone, two in the lung, five in the liver, two in the local site, and three in the lymph nodes) during the follow-up period. No statistically significant difference was observed in the cause-specific survival (P ⫽ 0.889; Fig. 1C) or overall survival (P ⫽ 0.532; Fig. 1D) rate. For all patients, advanced tumor stage and grade increased the risk of metastases and death (Fig. 2).
COMMENT With recent technical improvements, the rate of complications with LNU has decreased. Several investigators have introduced laparoscopic procedures for radical nephroureterectomy and suggested their benefit for patient recovery with disease control comparable to that of traditional open surgery on the basis of the results of comparative studies (Table 3). However, the number of patients in each study has been relatively small. In addi459
Figure 2. (A) Progression-free survival and (B) overall survival according to stage. (C) Progression-free survival and (D) overall survival according to cancer grade. Statistically significant better survival was observed in patients with lower stage (P ⬍0.001) and in patients with lower grade (P ⬍0.01).
Table 3. Results of comparative studies between LNU and ONU for upper urinary tract TCC Investigator Shalhav et al.6 McNeill et al.7 Kawauchi et al.8 Klingler et al.9 Rassweiler et al.14 Bariol et al.11 Tsujihata et al.13 Present study
LNU/ONU (n)
Bladder Recurrence (%)
Local Recurrence (%)
Distant Metastasis (%)
2-yr Survival (%)
13/13 25/42 34/34 19/15 23/21 26/42 25/24 58/166
23/53.8 28/42 9/38 10.5/13.3 34.8/14.4 28/42 28/33.3 32.8/38.0
15.3/0 8/15.4 0/0 5.3/6.6 0/4.8 4/15 n.a. 2.0*/1.0
15.3/23 28/18 6.0/9.0 10.5/6.6 17.4/28.5 28/18 0/8 17.2/19.9
77/69 74/68 NA 94.7/93.7 89/63 NA NA 85.2/87.0
TCC ⫽ transitional cell carcinoma; NA ⫽ not available; other abbreviations as in Table 1. * Port site recurrence.
tion, the oncologic background (eg, history of, or concomitant, bladder tumor) and surgical procedure, especially in terms of distal ureterectomy, which could affect the oncologic outcome, have differed in those studies. Regarding the radical nephroureterectomy procedure, the disposal method of the distal ureter and bladder cuff is one point of controversy. A number of different approaches to the distal ureter have been described with varying degrees of oncologic safety. Although using minimally invasive techniques is commendable in an effort to decrease postoperative morbidity, we believe that establishing better oncologic outcomes is a more important issue. A number of cases of local recurrence have been described using the “pluck” technique. We have already 460
reported that nephroureterectomy with transurethral stripping has a significantly greater intravesical recurrence rate statistically than does conventional nephroureterectomy with a bladder cuff.16 Therefore, every patient in the present series underwent removal of the distal ureter with an open technique. The low rate of local recurrence in the present study has justified this policy. Our present study also had some problems because it was retrospective. First, we had no definitive criteria for choosing the surgical procedure, including the indication for lymphadenectomy, which might have caused the difference in the mean follow-up periods between the two groups. Second, the follow-up period in the LNU group UROLOGY 69 (3), 2007
might not have been long enough to evaluate the survival. However, our study does bring some precious information regarding the oncologic outcome after surgery of upper urinary tract TCC, including the following. Our series did not include patients with a history of, or concomitant, bladder tumor. The LNU and ONU groups were equivalent with respect to the grade and stage of the tumor removed, which could affect bladder recurrence, development of metastases, and survival. Our study is unique in this point of comparison with previous reports. With this similar background, the incidence of metastases and bladder recurrence were within the expected range17 and were equal in the LNU and ONU groups. Predictors of bladder recurrence could not be identified. The survival data have confirmed that the clinical progression reflected the aggressive nature of the initial disease and not the surgical procedure, although the follow-up period for LNU might be relatively short to draw such a conclusion. Advanced stage and grade have been confirmed as predictors of metastatic recurrence and death. Our results suggest that LNU with open ureterectomy seems to be a safe alternative for the treatment of upper urinary tract TCC with cancer control similar to that of ONU. One patient experienced a port site recurrence. Rassweiler et al.5 reported 6 cases of port site metastasis (1.6%) in 377 patients, occurring 3 to 12 months after laparoscopy. Klingler et al.9 noted that the use of the ultrasonic shears for tissue dissection results in uncontrollable tissue and fluid evaporation that might be an origin of cancer cell spread. In our case, extravasated urine, which might have contained cancer cells, was present in the surgical field. This was one possible reason for local recurrence. In such a case, the use of ultrasonic shears might be avoided for scattering cancer cells during LNU.
CONCLUSIONS In the surgical management of upper tract TCC, LNU does not negatively affect oncologic control and can be an alternative modality. The tumor stage and grade are, however, important prognostic factors in the development of metastases and cancer-specific mortality. The results from longer term studies are warranted to clarify this issue.
UROLOGY 69 (3), 2007
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