- Email: [email protected]
Is Radical Nephroureterectomy and Lymph Node Dissection Necessary for Upper-tract TCC?
EUROPEAN UROLOGY SUPPLEMENTS 9 (2010) 442–445
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Is Radical Nephroureterectomy and Lymph Node Dissection Necessary for Upper-tract TCC? S. Joniau a,*, B. Van Cleynenbreugel a, W. Blyweert a, I. Romics b, H. Van Poppel a a
Department of Urology, University Hospital Leuven, K.U.Leuven, Belgium
b
Urology, Semmelweis University, H-1082 Budapest, Hungary
Article info
Abstract
Keywords: Transitional cell carcinoma Upper-tract Lymph node dissection Nephroureterectomy
Upper urinary tract transitional cell carcinoma (UUTT) is a rare condition, and there are no internationally validated guidelines on how to treat these lesions. Invasive and metastatic disease is more common than in bladder transitional cell carcinoma (TCC). Ureteroscopy with biopsy and computed tomography (CT) urography add diagnostic accuracy; however, in high-grade lesions, muscle invasion and lymph nodes may be missed in 10–40% of the cases. Open nephroureterectomy (NU) remains the gold standard against which other approaches should be compared. Laparoscopic NU is becoming widely accepted as a minimally invasive alternative, delivering similar oncologic outcomes at short or intermediate follow-up. For lowstage, low-grade lesions, for solitary lesions and in imperative indications, nephronsparing surgery (NSS) may be offered to the patient. The role of lymphadenectomy lies in correct staging, and its therapeutic benefit remains controversial. Ideally, large international, prospective trials should assess the best management of UUTT.
Please visit www.eu-acme.org/ europeanurology to read and answer questions on-line. The EU-ACME credits will then be attributed automatically.
1.
# 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. University Hospital Leuven, Herestraat 49, 3000 Leuven, Belgium. Tel. +32 16 34.66.87; Fax: +32 16 34.69.31. E-mail address: [email protected] (S. Joniau).
Introduction
The incidence of upper urinary tract transitional cell carcinoma (UUTT) is 0.6–1.1 out of 100 000 per year. UUTT constitutes 5–7% of all urothelial tumours, with 4% located in the renal pelvis and calices and about 3% in the ureter. It seldom presents as bilateral disease (2–4%) [1]. Eighty percent of UUTT is preceded by bladder cancer (BCa). Patients who present with superficial bladder transitional cell carcinoma (TCC) have a 2–4% incidence of metachronous upper-tract tumours. Incidence of metachronous UUTT increases with time: 2.7% within 8–10 yr and 8.1% within 10–15 yr. Carcinoma in situ (CIS) of the bladder is the highest risk factor for upper-tract recurrence (up to 21%) [2,3]. Of patients who present with initial UUTT, 20–75% will develop metachronous BCa. Most of these will be diagnosed within 2 yr of the diagnosis of initial UUTT. These
observations point to the need for close surveillance of the bladder in patients with UUTT [4]. The natural history of UUTT has been reported to be more aggressive than bladder TCC. Muscle-invasive disease at presentation is common and reported to be 40% more common than in BCa. Up to 50% of renal pelvis and ureteral tumours are invasive, and 19% present with metastatic disease [5]. The disease-specific survival (DSS) in UUTT depends on the TNM stage of the disease. In situ and superficial UUTT have a 89–95% 5-yr DSS, while regional disease and muscle-invasive localised disease have a 63% 5-yr DSS. Patients who present with metastatic disease have a poor prognosis, with 16% DSS at 5 yr [6]. It has been questioned whether tumour localisation constitutes a prognostic factor in patients with UUTT. In a multicentre analysis of 1249 patients with UUTT, Raman and co-workers showed that location of TCC within the renal pelvis had no
1569-9056/$ – see front matter # 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.eursup.2010.03.005
EUROPEAN UROLOGY SUPPLEMENTS 9 (2010) 442–445
different recurrence-free survival (RFS) or DSS compared to location within the ureter ( p = 0.7 and p = 0.8, respectively). In the subgroup of patients who presented with organconfined UUTT, they noted significant differences in RFS and DSS compared to patients with renal pelvis TCC versus ureteric TCC ( p = 0.02 and p = 0.02, respectively). However, when tumour localisation was entered in a Cox multivariable analysis, tumour location had no predictive significance when corrected for pT classification, tumour grade, and pN classification (hazard ratio: 1.22; 95% confidence interval, 0.942–1.58; p = 0.133) [7]. 2. Rationale for radical treatment of upper urinary tract transitional cell carcinoma Open nephroureterectomy (NU) with en bloc excision of the ureter using a periureteral bladder cuff has long been considered the gold standard treatment of UUTT. However, TCC of the bladder is managed conservatively in most patients. The question now rises whether conservative management comparable to TCC of the bladder can be used in UUTT. There are several arguments against this. First, staging accuracy of computed tomography (CT) urography for UUTT is only 60%. CT may miss lesions <5 mm and is not ideal for lymph node staging. Nevertheless, detection rates by CT urography are much better than intravenous urography, and sensitivity for detection is at 96%, while specificity for detection approaches 100% [8]. Second, although ureteroscopy with biopsy may show a good correlation of biopsy grade with surgical grade, the correlation of biopsy grade with surgical stage is only moderate. Keeley et al showed a 90% grade correlation for low-grade tumours and a 92% correlation in high-grade tumours. Of grade I–II lesions on biopsy, 87% had low-stage disease on final histopathology, while in high-grade lesions, only 67% will have high-stage disease on final histopathology [9]. Thus, muscular invasion may be missed by both CT urography and biopsy, and CT may miss lymph node invasion. An important group of patients presenting with UUTT will be at risk for understaging, and conservative treatment or kidney-sparing treatments in those patients may be largely insufficient. Another argument in favour of radical surgery is that recurrence of UUTT is common after local therapy. Ipsilateral recurrence rates after endoscopic resection have been reported to be 31–65%. Recurrence of TCC in a retained stump after NU has been reported to be 10–70%. Furthermore, recurrence is invariably distal to the primary tumour. Contralateral upper-tract tumours are rare [4]. These points may further argue for radical treatment of UUTT. 3. Is there a role for nephron-sparing surgery in upper urinary tract transitional cell carcinoma? There is a general consensus that for low-stage, low-grade lesions, for solitary lesions; and in absolute indications, nephron-sparing surgery (NSS) may be offered to the patient. However, this surgery may be technically demanding, and
443
regular upper-tract follow up is mandatory. A detailed description hereof is provided elsewhere in this issue. 4.
Open or laparoscopic nephroureterectomy?
In the last decade, we have witnessed a dramatic shift in surgical approach for kidney and prostate cancer in favour of conventional laparoscopy and robot-assisted laparoscopic surgery. The same has happened in the field of UUTT, where in many expert institutions laparoscopic NU is now preferred over the open approach. However, several questions remain unanswered. Some surgeons prefer the transperitoneal approach over the retroperitoneal approach. Some prefer a full laparoscopic approach, others a hand-assisted approach. The technique of excision of the distal ureter and bladder cuff remains another controversial issue. Several techniques have been described, such as the Stapling technique, the Pluck technique, ureteral stripping, and open excision, and the issue was recently reviewed by Srirangam et al [10]. Whatever the approach and whichever route is chosen, sound oncologic surgical principles should remain identical: a complete en bloc resection with intact bladder cuff should be performed, avoiding tumour seeding. Table 1 lists advantages, disadvantages, and contraindications of the different approaches to the distal ureter and bladder cuff during laparoscopic NU [11–15]. There are some limitations in the urologic literature regarding comparison between laparoscopic NU and open NU. In most of the studies on laparoscopic NU, follow-up is short, patient numbers are limited, and the setting is almost exclusively retrospective. However, all laparoscopic techniques show good results—comparable to open NU. There seems to be a general consensus on the management of the distal ureter in favour of open cuff resection, implying that after laparoscopically freeing the kidney and controlling the hilar vessels, the kidney is placed in the iliac fossa and the laparoscopic access wounds closed. The patient is then usually repositioned, and a Pfannenstiel or oblique lower abdominal incision is made through which the kidney and ureter are delivered and the distal ureterectomy and bladder cuff resection completed. Table 2 provides an overview of comparative series of laparoscopic or hand-assisted laparoscopic versus open NU for UUTT. 5. What is the role of lymphadenectomy in nephroureterectomy? In a recent multicenter analysis of 1130 patients undergoing open NU, Roscigno et al noted 25.4% positive lymph nodes in the 552 patients who underwent lymphadenectomy. In contrast, 578 (51.1%) patients did not undergo lymph node dissection (LND), the reason being unclear. In a further subanalysis, the DSS of patients who did not receive LND was consistently worse than patients who had undergone LND and were N0 at histopathology. This effect was even stronger in those patients with muscle-invasive UUTT [23]. This study clearly showed the value of a LND in staging and
444
EUROPEAN UROLOGY SUPPLEMENTS 9 (2010) 442–445
Table 1 – Advantages, disadvantages and contraindications of different surgical techniques for handling the distal ureter Technique Stapler technique
Advantages Urinary tract remains closed
Pluck technique (TURUO)
Stripping of the ureter
Open bladder cuff resection
Intact, en bloc removal Wide excision of bladder cuff possible
Disadvantages
Contraindications
Tumoural implations in staple line No intraoperative confirmation of complete resection Damage to contralateral ureteral orifice Risk of stone formation Retroperitoneal tumour seeding (case reports) Retention of distal ureteral segment
Exposition of bladder and urethra to the mucosa of the stripped ureter Retention of the intramural ureter Two surgical specimens Risk of damage to the contralateral ureteral orifice (extravesical technique) Possibility of incomplete resection (extravesical technique) Difficult in obese patients; following RT
Distal ureteral tumours Bladder tumours near ureteral orifice
TCC of the distal ureter and bladder TCC in the proximity of UVJ Active bladder TCC History of RT Ureter TCC Active bladder TCC (risk of extravasation) Fibrosis of the ureter (lithiasis, stricture, RT) Active bladder TCC
TURUO = transurethral resection of the ureteral orifice; TCC = transitional cell carcinoma; UVJ = ureterovesical junction; RT = radiation therapy
Table 2 – Literature overview of studies comparing laparoscopic versus open nephroureterectomy (adapted from [4]) Series
McNeill [16] Seifman [17] Raman [18] Roupreˆt [19] Manabe [20] Gill [21] Shalhav [22]
No. patients, laparoscopic/open
Follow-up, mo, laparoscopic/open
Recurrence rate, %*, laparoscopic/open
25/42 16/11 38/52 26/20 58/166 42/35 25/17
33/42 19/16 32/52 78/69 14/28 11/34 24/43
NR 19/64 40/50 54/20 25/18 23/37 23/54
DSS, laparoscopic/open 84/79 NR 97/83 90/62 85/87 97/87 77/77
DSS = disease-specific survival; NR = not reported All sites of recurrence (bladder, contralateral upper tract, metastatic)
*
outcome assessment. However, the study did not provide insight into a possible benefit of an extended LND in patients with UUTT. In fact, the therapeutic benefit of a lymphadenectomy in UUTT remains controversial. Brausi et al found a positive correlation between LND and survival; Roscigno et al did not [23–25]. However, as mentioned above, LND adds to correct staging and delivers prognostic information. It is recommended in high-grade upper-tract lesions and in clinical T2 to clinical T4 lesions. In a further analysis of the patients, Roscigno et al clearly stated that at least eight nodes should be removed to achieve 75% accuracy of probability of finding one or more positive nodes [23]. Thus far, predictive tools are absent. 6.
Complete urinary tract extirpation
Complete urinary tract extirpation (CUTE) is a reasonable option in a highly selected patient population with T1–3 bladder TCC/CIS and massive bilateral UUTT with no metastases or unilateral UUTT with an afunctional contralateral kidney. Recently, Blyweert et al presented their results of CUTE in 17 patients. This is so far the largest series of CUTE; from the analysis, the feasibility of this elaborate surgery was shown. There was, however, an elevated perioperative risk, with three perioperative mortalities.
Major non-lethal early complications were identified in four other patients. The mean follow-up was 39 mo. During follow-up, kidney transplantation was performed on an ileal conduit in four patients. Patients who were on preoperative immunotherapy (cardiac transplantation [n = 2] or kidney transplantation [n = 3]) had the worst outcomes [26]. 7.
Conclusions
UTCC is a rare condition, and literature on this disease is rather scarce. There are no internationally validated guidelines on how to treat these lesions. Invasive and metastatic disease is more common than in bladder TCC. Ureteroscopy with biopsy and CT urography add diagnostic accuracy, but in high-grade lesions, muscle invasion and lymph nodes may be missed in 10–40% of the cases. The treatment of UUTT should be tailored both to patient factors and tumour factors. Open NU remains the gold standard against which other approaches should be compared. Laparoscopic NU is becoming widely accepted as a minimally invasive alternative, delivering similar oncologic outcomes at short and intermediate follow-up. For low-stage, low-grade lesions; solitary lesions; and in absolute indications, NSS may be offered to the patient.
445
EUROPEAN UROLOGY SUPPLEMENTS 9 (2010) 442–445
The role of lymphadenectomy lies in correct staging. Its likely therapeutic benefit remains controversial. Ideally, large international, prospective trials should assess the best management of UUTT. Of note in the last 2 yr, multicenter collaborative, retrospective studies have been initiated and have provided new insights into this infrequent condition and its management [7,23,24]. These may be used as a basis to initiate further prospective studies.
[12] Palou J, Caparro´s J, Orsola A, Xavier B, Vicente J. Transurethral resection of the intramural ureter as the first step of nephroureterectomy. J Urol 1995;154:43–4. [13] Geavlete P, Georgescu D, Bancu S, Mirciulescu V. Endoscopic ureteral procedures for one-step nephroureterectomy: experience in 100 cases. J Endourol 2007;21:1019–24. [14] Laguna MP, de la Rosette JJMCH. The endoscopic approach to the distal ureter in nephroureterectomy for upper urinary tract tumor. J Urol 2001;166:2017–22. [15] Taweemonkongsap T, Nualyong C, Amornvesukit T, et al. Outcomes
Conflicts of interest
of surgical treatment for upper urinary tract transitional cell carcinoma: comparison of retroperitoneoscopic and open nephro-
The authors have nothing to disclose.
ureterectomy. World J Surg Oncol 2008;6:3. [16] McNeill SA, Chrisofos M, Tolley DA. The long-term outcome after laparoscopic nephroureterectomy: a comparison with open
Funding support
nephroureterectomy. BJU Int 2000;86:619–23. [17] Seifman BD, Montie JE, Wolf Jr JS. Prospective comparison between
None.
hand-assisted laparoscopic and open surgical nephroureterectomy for urothelial cell carcinoma. Urology 2001;57:133–7. [18] Raman JD, Palese MA, Ng CK, et al. Hand-assisted laparoscopic
References [1] Melamed MR, Reuter VE. Pathology and staging of urothelial tumors
nephroureterectomy for upper urinary tract transitional cell carcinoma. JSLS 2006;10:432–8. [19] Roupreˆt M, Hupertan V, Sanderson KM, et al. Oncologic control after
of the kidney and ureter. Urol Clin North Am 1993;20:333–47.
open or laparoscopic nephroureterectomy for upper urinary tract
[2] Holma¨ng S, Johansson SL. Synchronous bilateral ureteral and renal
transitional cell carcinoma: a single center experience. Urology
pelvic carcinomas: incidence, etiology, treatment and outcome. Cancer 2004;101:741–7. [3] Rabbani F, Perrotti M, Russo P, Herr HW. Upper-tract tumors after
2007;69:656–61. [20] Manabe D, Saika T, Ebara S, et al., Okayama Urological Research Group, Okayama, Japan. Comparative study of oncologic outcome
an initial diagnosis of bladder cancer: argument for long-term
of
surveillance. J Clin Oncol 2001;19:94–100.
ureterectomy for upper urinary tract transitional cell carcinoma.
[4] Raman JD, Scherr DS. Management of patients with upper urinary
laparoscopic
nephroureterectomy
and
standard
nephro-
Urology 2007;69:457–61.
tract transitional cell carcinoma. Nat Clin Pract Urol 2007;4:432–43.
[21] Gill IS, Sung GT, Hobart MG, et al. Laparoscopic radical nephro-
[5] Stewart GD, Bariol SV, Grigor KM, Tolley DA, McNeill SA. A compar-
ureterectomy for upper tract transitional cell carcinoma: the Cleve-
ison of the pathology of transitional cell carcinoma of the bladder and upper urinary tract. BJU Int 2005;95:791–3. [6] Munoz JJ, Ellison LM. Upper tract urothelial neoplasms: incidence and survival during the last 2 decades. J Urol 2000;164:1523–5. [7] Raman JD, Ng CK, Scherr DS, et al. Impact of tumor location on
land Clinic experience. J Urol 2000;164:1513–22. [22] Shalhav AL, Dunn MD, Portis AJ, Elbahnasy AM, McDougall EM, Clayman RV. Laparoscopic nephroureterectomy for upper tract transitional cell cancer: the Washington University experience. J Urol 2000;163:1100–4.
prognosis for patients with upper tract urothelial carcinoma man-
[23] Roscigno M, Shariat SF, Margulis V, et al. The extent of lymphade-
aged by radical nephroureterectomy. Eur Urol. In press. DOI:10.1016/
nectomy seems to be associated with better survival in patients
j.eururo.2009.07.002.
with nonmetastatic upper-tract urothelial carcinoma: how many
[8] Vikram R, Sandler CM, Ng CS. Imaging and staging of transitional cell carcinoma: part 2, upper urinary tract. AJR Am J Roentgenol 2009;192:1488–93. [9] Keeley FX, Kulp DA, Bibbo M, McCue PA, Bagley DH. Diagnostic accuracy of ureteroscopic biopsy in upper tract transitional cell carcinoma. J Urol 1997;157:33–7.
lymph nodes should be removed? Eur Urol 2009;56:512–8. [24] Roscigno M, Cozzarini C, Bertini R, et al. Prognostic value of lymph node dissection in patients with muscle-invasive transitional cell carcinoma of the upper urinary tract. Eur Urol 2008;53: 794–802. [25] Brausi MA, Gavioli M, De Luca G, et al. Retroperitoneal lymph node
[10] Srirangam SJ, van Cleynenbreugel B, van Poppel H. Laparoscopic
dissection (RPLD) in conjunction with nephroureterectomy in the
nephroureterectomy: the distal ureteral dilemma. Adv Urol. In
treatment of infiltrative transitional cell carcinoma (TCC) of the
press. DOI:10.1155/2009/316807.
upper urinary tract: impact on survival. Eur Urol 2007;52:1414–9.
[11] Jarrett TW, Chan DY, Cadeddu JA, Kavoussi LR. Laparoscopic
[26] Blyweert W, Joniau S, Van Poppel H. Complete urinary tract extirpa-
nephroureterectomy for the treatment of transitional cell carci-
tion: a single centre series of 17 patients. Urology 2009;74(Suppl 4):
noma of the upper urinary tract. Urology 2001;57:448–53.
S110.
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Is Radical Nephroureterectomy and Lymph Node Dissection Necessary for Upper-tract TCC? S. Joniau a,*, B. Van Cleynenbreugel a, W. Blyweert a, I. Romics b, H. Van Poppel a a
Department of Urology, University Hospital Leuven, K.U.Leuven, Belgium
b
Urology, Semmelweis University, H-1082 Budapest, Hungary
Article info
Abstract
Keywords: Transitional cell carcinoma Upper-tract Lymph node dissection Nephroureterectomy
Upper urinary tract transitional cell carcinoma (UUTT) is a rare condition, and there are no internationally validated guidelines on how to treat these lesions. Invasive and metastatic disease is more common than in bladder transitional cell carcinoma (TCC). Ureteroscopy with biopsy and computed tomography (CT) urography add diagnostic accuracy; however, in high-grade lesions, muscle invasion and lymph nodes may be missed in 10–40% of the cases. Open nephroureterectomy (NU) remains the gold standard against which other approaches should be compared. Laparoscopic NU is becoming widely accepted as a minimally invasive alternative, delivering similar oncologic outcomes at short or intermediate follow-up. For lowstage, low-grade lesions, for solitary lesions and in imperative indications, nephronsparing surgery (NSS) may be offered to the patient. The role of lymphadenectomy lies in correct staging, and its therapeutic benefit remains controversial. Ideally, large international, prospective trials should assess the best management of UUTT.
Please visit www.eu-acme.org/ europeanurology to read and answer questions on-line. The EU-ACME credits will then be attributed automatically.
1.
# 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. University Hospital Leuven, Herestraat 49, 3000 Leuven, Belgium. Tel. +32 16 34.66.87; Fax: +32 16 34.69.31. E-mail address: [email protected] (S. Joniau).
Introduction
The incidence of upper urinary tract transitional cell carcinoma (UUTT) is 0.6–1.1 out of 100 000 per year. UUTT constitutes 5–7% of all urothelial tumours, with 4% located in the renal pelvis and calices and about 3% in the ureter. It seldom presents as bilateral disease (2–4%) [1]. Eighty percent of UUTT is preceded by bladder cancer (BCa). Patients who present with superficial bladder transitional cell carcinoma (TCC) have a 2–4% incidence of metachronous upper-tract tumours. Incidence of metachronous UUTT increases with time: 2.7% within 8–10 yr and 8.1% within 10–15 yr. Carcinoma in situ (CIS) of the bladder is the highest risk factor for upper-tract recurrence (up to 21%) [2,3]. Of patients who present with initial UUTT, 20–75% will develop metachronous BCa. Most of these will be diagnosed within 2 yr of the diagnosis of initial UUTT. These
observations point to the need for close surveillance of the bladder in patients with UUTT [4]. The natural history of UUTT has been reported to be more aggressive than bladder TCC. Muscle-invasive disease at presentation is common and reported to be 40% more common than in BCa. Up to 50% of renal pelvis and ureteral tumours are invasive, and 19% present with metastatic disease [5]. The disease-specific survival (DSS) in UUTT depends on the TNM stage of the disease. In situ and superficial UUTT have a 89–95% 5-yr DSS, while regional disease and muscle-invasive localised disease have a 63% 5-yr DSS. Patients who present with metastatic disease have a poor prognosis, with 16% DSS at 5 yr [6]. It has been questioned whether tumour localisation constitutes a prognostic factor in patients with UUTT. In a multicentre analysis of 1249 patients with UUTT, Raman and co-workers showed that location of TCC within the renal pelvis had no
1569-9056/$ – see front matter # 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.eursup.2010.03.005
EUROPEAN UROLOGY SUPPLEMENTS 9 (2010) 442–445
different recurrence-free survival (RFS) or DSS compared to location within the ureter ( p = 0.7 and p = 0.8, respectively). In the subgroup of patients who presented with organconfined UUTT, they noted significant differences in RFS and DSS compared to patients with renal pelvis TCC versus ureteric TCC ( p = 0.02 and p = 0.02, respectively). However, when tumour localisation was entered in a Cox multivariable analysis, tumour location had no predictive significance when corrected for pT classification, tumour grade, and pN classification (hazard ratio: 1.22; 95% confidence interval, 0.942–1.58; p = 0.133) [7]. 2. Rationale for radical treatment of upper urinary tract transitional cell carcinoma Open nephroureterectomy (NU) with en bloc excision of the ureter using a periureteral bladder cuff has long been considered the gold standard treatment of UUTT. However, TCC of the bladder is managed conservatively in most patients. The question now rises whether conservative management comparable to TCC of the bladder can be used in UUTT. There are several arguments against this. First, staging accuracy of computed tomography (CT) urography for UUTT is only 60%. CT may miss lesions <5 mm and is not ideal for lymph node staging. Nevertheless, detection rates by CT urography are much better than intravenous urography, and sensitivity for detection is at 96%, while specificity for detection approaches 100% [8]. Second, although ureteroscopy with biopsy may show a good correlation of biopsy grade with surgical grade, the correlation of biopsy grade with surgical stage is only moderate. Keeley et al showed a 90% grade correlation for low-grade tumours and a 92% correlation in high-grade tumours. Of grade I–II lesions on biopsy, 87% had low-stage disease on final histopathology, while in high-grade lesions, only 67% will have high-stage disease on final histopathology [9]. Thus, muscular invasion may be missed by both CT urography and biopsy, and CT may miss lymph node invasion. An important group of patients presenting with UUTT will be at risk for understaging, and conservative treatment or kidney-sparing treatments in those patients may be largely insufficient. Another argument in favour of radical surgery is that recurrence of UUTT is common after local therapy. Ipsilateral recurrence rates after endoscopic resection have been reported to be 31–65%. Recurrence of TCC in a retained stump after NU has been reported to be 10–70%. Furthermore, recurrence is invariably distal to the primary tumour. Contralateral upper-tract tumours are rare [4]. These points may further argue for radical treatment of UUTT. 3. Is there a role for nephron-sparing surgery in upper urinary tract transitional cell carcinoma? There is a general consensus that for low-stage, low-grade lesions, for solitary lesions; and in absolute indications, nephron-sparing surgery (NSS) may be offered to the patient. However, this surgery may be technically demanding, and
443
regular upper-tract follow up is mandatory. A detailed description hereof is provided elsewhere in this issue. 4.
Open or laparoscopic nephroureterectomy?
In the last decade, we have witnessed a dramatic shift in surgical approach for kidney and prostate cancer in favour of conventional laparoscopy and robot-assisted laparoscopic surgery. The same has happened in the field of UUTT, where in many expert institutions laparoscopic NU is now preferred over the open approach. However, several questions remain unanswered. Some surgeons prefer the transperitoneal approach over the retroperitoneal approach. Some prefer a full laparoscopic approach, others a hand-assisted approach. The technique of excision of the distal ureter and bladder cuff remains another controversial issue. Several techniques have been described, such as the Stapling technique, the Pluck technique, ureteral stripping, and open excision, and the issue was recently reviewed by Srirangam et al [10]. Whatever the approach and whichever route is chosen, sound oncologic surgical principles should remain identical: a complete en bloc resection with intact bladder cuff should be performed, avoiding tumour seeding. Table 1 lists advantages, disadvantages, and contraindications of the different approaches to the distal ureter and bladder cuff during laparoscopic NU [11–15]. There are some limitations in the urologic literature regarding comparison between laparoscopic NU and open NU. In most of the studies on laparoscopic NU, follow-up is short, patient numbers are limited, and the setting is almost exclusively retrospective. However, all laparoscopic techniques show good results—comparable to open NU. There seems to be a general consensus on the management of the distal ureter in favour of open cuff resection, implying that after laparoscopically freeing the kidney and controlling the hilar vessels, the kidney is placed in the iliac fossa and the laparoscopic access wounds closed. The patient is then usually repositioned, and a Pfannenstiel or oblique lower abdominal incision is made through which the kidney and ureter are delivered and the distal ureterectomy and bladder cuff resection completed. Table 2 provides an overview of comparative series of laparoscopic or hand-assisted laparoscopic versus open NU for UUTT. 5. What is the role of lymphadenectomy in nephroureterectomy? In a recent multicenter analysis of 1130 patients undergoing open NU, Roscigno et al noted 25.4% positive lymph nodes in the 552 patients who underwent lymphadenectomy. In contrast, 578 (51.1%) patients did not undergo lymph node dissection (LND), the reason being unclear. In a further subanalysis, the DSS of patients who did not receive LND was consistently worse than patients who had undergone LND and were N0 at histopathology. This effect was even stronger in those patients with muscle-invasive UUTT [23]. This study clearly showed the value of a LND in staging and
444
EUROPEAN UROLOGY SUPPLEMENTS 9 (2010) 442–445
Table 1 – Advantages, disadvantages and contraindications of different surgical techniques for handling the distal ureter Technique Stapler technique
Advantages Urinary tract remains closed
Pluck technique (TURUO)
Stripping of the ureter
Open bladder cuff resection
Intact, en bloc removal Wide excision of bladder cuff possible
Disadvantages
Contraindications
Tumoural implations in staple line No intraoperative confirmation of complete resection Damage to contralateral ureteral orifice Risk of stone formation Retroperitoneal tumour seeding (case reports) Retention of distal ureteral segment
Exposition of bladder and urethra to the mucosa of the stripped ureter Retention of the intramural ureter Two surgical specimens Risk of damage to the contralateral ureteral orifice (extravesical technique) Possibility of incomplete resection (extravesical technique) Difficult in obese patients; following RT
Distal ureteral tumours Bladder tumours near ureteral orifice
TCC of the distal ureter and bladder TCC in the proximity of UVJ Active bladder TCC History of RT Ureter TCC Active bladder TCC (risk of extravasation) Fibrosis of the ureter (lithiasis, stricture, RT) Active bladder TCC
TURUO = transurethral resection of the ureteral orifice; TCC = transitional cell carcinoma; UVJ = ureterovesical junction; RT = radiation therapy
Table 2 – Literature overview of studies comparing laparoscopic versus open nephroureterectomy (adapted from [4]) Series
McNeill [16] Seifman [17] Raman [18] Roupreˆt [19] Manabe [20] Gill [21] Shalhav [22]
No. patients, laparoscopic/open
Follow-up, mo, laparoscopic/open
Recurrence rate, %*, laparoscopic/open
25/42 16/11 38/52 26/20 58/166 42/35 25/17
33/42 19/16 32/52 78/69 14/28 11/34 24/43
NR 19/64 40/50 54/20 25/18 23/37 23/54
DSS, laparoscopic/open 84/79 NR 97/83 90/62 85/87 97/87 77/77
DSS = disease-specific survival; NR = not reported All sites of recurrence (bladder, contralateral upper tract, metastatic)
*
outcome assessment. However, the study did not provide insight into a possible benefit of an extended LND in patients with UUTT. In fact, the therapeutic benefit of a lymphadenectomy in UUTT remains controversial. Brausi et al found a positive correlation between LND and survival; Roscigno et al did not [23–25]. However, as mentioned above, LND adds to correct staging and delivers prognostic information. It is recommended in high-grade upper-tract lesions and in clinical T2 to clinical T4 lesions. In a further analysis of the patients, Roscigno et al clearly stated that at least eight nodes should be removed to achieve 75% accuracy of probability of finding one or more positive nodes [23]. Thus far, predictive tools are absent. 6.
Complete urinary tract extirpation
Complete urinary tract extirpation (CUTE) is a reasonable option in a highly selected patient population with T1–3 bladder TCC/CIS and massive bilateral UUTT with no metastases or unilateral UUTT with an afunctional contralateral kidney. Recently, Blyweert et al presented their results of CUTE in 17 patients. This is so far the largest series of CUTE; from the analysis, the feasibility of this elaborate surgery was shown. There was, however, an elevated perioperative risk, with three perioperative mortalities.
Major non-lethal early complications were identified in four other patients. The mean follow-up was 39 mo. During follow-up, kidney transplantation was performed on an ileal conduit in four patients. Patients who were on preoperative immunotherapy (cardiac transplantation [n = 2] or kidney transplantation [n = 3]) had the worst outcomes [26]. 7.
Conclusions
UTCC is a rare condition, and literature on this disease is rather scarce. There are no internationally validated guidelines on how to treat these lesions. Invasive and metastatic disease is more common than in bladder TCC. Ureteroscopy with biopsy and CT urography add diagnostic accuracy, but in high-grade lesions, muscle invasion and lymph nodes may be missed in 10–40% of the cases. The treatment of UUTT should be tailored both to patient factors and tumour factors. Open NU remains the gold standard against which other approaches should be compared. Laparoscopic NU is becoming widely accepted as a minimally invasive alternative, delivering similar oncologic outcomes at short and intermediate follow-up. For low-stage, low-grade lesions; solitary lesions; and in absolute indications, NSS may be offered to the patient.
445
EUROPEAN UROLOGY SUPPLEMENTS 9 (2010) 442–445
The role of lymphadenectomy lies in correct staging. Its likely therapeutic benefit remains controversial. Ideally, large international, prospective trials should assess the best management of UUTT. Of note in the last 2 yr, multicenter collaborative, retrospective studies have been initiated and have provided new insights into this infrequent condition and its management [7,23,24]. These may be used as a basis to initiate further prospective studies.
[12] Palou J, Caparro´s J, Orsola A, Xavier B, Vicente J. Transurethral resection of the intramural ureter as the first step of nephroureterectomy. J Urol 1995;154:43–4. [13] Geavlete P, Georgescu D, Bancu S, Mirciulescu V. Endoscopic ureteral procedures for one-step nephroureterectomy: experience in 100 cases. J Endourol 2007;21:1019–24. [14] Laguna MP, de la Rosette JJMCH. The endoscopic approach to the distal ureter in nephroureterectomy for upper urinary tract tumor. J Urol 2001;166:2017–22. [15] Taweemonkongsap T, Nualyong C, Amornvesukit T, et al. Outcomes
Conflicts of interest
of surgical treatment for upper urinary tract transitional cell carcinoma: comparison of retroperitoneoscopic and open nephro-
The authors have nothing to disclose.
ureterectomy. World J Surg Oncol 2008;6:3. [16] McNeill SA, Chrisofos M, Tolley DA. The long-term outcome after laparoscopic nephroureterectomy: a comparison with open
Funding support
nephroureterectomy. BJU Int 2000;86:619–23. [17] Seifman BD, Montie JE, Wolf Jr JS. Prospective comparison between
None.
hand-assisted laparoscopic and open surgical nephroureterectomy for urothelial cell carcinoma. Urology 2001;57:133–7. [18] Raman JD, Palese MA, Ng CK, et al. Hand-assisted laparoscopic
References [1] Melamed MR, Reuter VE. Pathology and staging of urothelial tumors
nephroureterectomy for upper urinary tract transitional cell carcinoma. JSLS 2006;10:432–8. [19] Roupreˆt M, Hupertan V, Sanderson KM, et al. Oncologic control after
of the kidney and ureter. Urol Clin North Am 1993;20:333–47.
open or laparoscopic nephroureterectomy for upper urinary tract
[2] Holma¨ng S, Johansson SL. Synchronous bilateral ureteral and renal
transitional cell carcinoma: a single center experience. Urology
pelvic carcinomas: incidence, etiology, treatment and outcome. Cancer 2004;101:741–7. [3] Rabbani F, Perrotti M, Russo P, Herr HW. Upper-tract tumors after
2007;69:656–61. [20] Manabe D, Saika T, Ebara S, et al., Okayama Urological Research Group, Okayama, Japan. Comparative study of oncologic outcome
an initial diagnosis of bladder cancer: argument for long-term
of
surveillance. J Clin Oncol 2001;19:94–100.
ureterectomy for upper urinary tract transitional cell carcinoma.
[4] Raman JD, Scherr DS. Management of patients with upper urinary
laparoscopic
nephroureterectomy
and
standard
nephro-
Urology 2007;69:457–61.
tract transitional cell carcinoma. Nat Clin Pract Urol 2007;4:432–43.
[21] Gill IS, Sung GT, Hobart MG, et al. Laparoscopic radical nephro-
[5] Stewart GD, Bariol SV, Grigor KM, Tolley DA, McNeill SA. A compar-
ureterectomy for upper tract transitional cell carcinoma: the Cleve-
ison of the pathology of transitional cell carcinoma of the bladder and upper urinary tract. BJU Int 2005;95:791–3. [6] Munoz JJ, Ellison LM. Upper tract urothelial neoplasms: incidence and survival during the last 2 decades. J Urol 2000;164:1523–5. [7] Raman JD, Ng CK, Scherr DS, et al. Impact of tumor location on
land Clinic experience. J Urol 2000;164:1513–22. [22] Shalhav AL, Dunn MD, Portis AJ, Elbahnasy AM, McDougall EM, Clayman RV. Laparoscopic nephroureterectomy for upper tract transitional cell cancer: the Washington University experience. J Urol 2000;163:1100–4.
prognosis for patients with upper tract urothelial carcinoma man-
[23] Roscigno M, Shariat SF, Margulis V, et al. The extent of lymphade-
aged by radical nephroureterectomy. Eur Urol. In press. DOI:10.1016/
nectomy seems to be associated with better survival in patients
j.eururo.2009.07.002.
with nonmetastatic upper-tract urothelial carcinoma: how many
[8] Vikram R, Sandler CM, Ng CS. Imaging and staging of transitional cell carcinoma: part 2, upper urinary tract. AJR Am J Roentgenol 2009;192:1488–93. [9] Keeley FX, Kulp DA, Bibbo M, McCue PA, Bagley DH. Diagnostic accuracy of ureteroscopic biopsy in upper tract transitional cell carcinoma. J Urol 1997;157:33–7.
lymph nodes should be removed? Eur Urol 2009;56:512–8. [24] Roscigno M, Cozzarini C, Bertini R, et al. Prognostic value of lymph node dissection in patients with muscle-invasive transitional cell carcinoma of the upper urinary tract. Eur Urol 2008;53: 794–802. [25] Brausi MA, Gavioli M, De Luca G, et al. Retroperitoneal lymph node
[10] Srirangam SJ, van Cleynenbreugel B, van Poppel H. Laparoscopic
dissection (RPLD) in conjunction with nephroureterectomy in the
nephroureterectomy: the distal ureteral dilemma. Adv Urol. In
treatment of infiltrative transitional cell carcinoma (TCC) of the
press. DOI:10.1155/2009/316807.
upper urinary tract: impact on survival. Eur Urol 2007;52:1414–9.
[11] Jarrett TW, Chan DY, Cadeddu JA, Kavoussi LR. Laparoscopic
[26] Blyweert W, Joniau S, Van Poppel H. Complete urinary tract extirpa-
nephroureterectomy for the treatment of transitional cell carci-
tion: a single centre series of 17 patients. Urology 2009;74(Suppl 4):
noma of the upper urinary tract. Urology 2001;57:448–53.
S110.