Laparoscopic Retroperitoneal Lymph Node Dissection: Does It Still Have a Role in the Management of Clinical Stage I Nonseminomatous Testis Cancer? A European Perspective

european urology 54 (2008) 1004–1019

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Review – Testis Cancer

Laparoscopic Retroperitoneal Lymph Node Dissection: Does It Still Have a Role in the Management of Clinical Stage I Nonseminomatous Testis Cancer? A European Perspective Jens J. Rassweiler a,*, Walter Scheitlin a, Axel Heidenreich b, M. Pilar Laguna c, Gu¨nter Janetschek d a

Department of Urology, Klinikum Heilbronn, University of Heidelberg, Heidelberg, Germany Department of Urology, University of Cologne, Cologne, Germany c Department of Urology, Amsterdam Medical Centre, Amsterdam, The Netherlands d Department of Urology, Elisabethinen Hospital Linz, Linz, Austria b

Article info

Abstract

Article history: Accepted August 5, 2008 Published online ahead of print on August 13, 2008

Context: Laparoscopic retroperitoneal lymph node dissection (L-RPLND) is not recommended as standard tool in European Association of Urology (EAU) guidelines. Objective: To update the role of L-RPLND in patients with clinical stage I nonseminomatous germ cell tumour (NSGCT) compared to open retroperitoneal lymph node dissection (O-RPLND). Evidence acquisition: A systematic literature search from 1992 to 2008 was performed in Medline, EMBASE, and Cochrane. The largest series from each group was considered. Comparative analysis was based on raw data of series published in 2000 and later. Evidence synthesis: Results of >800 patients treated by L-RPLND reported in 34 articles were analyzed. Lymph node dissection (LND) was based on modified templates, removing an average of 16 (5–36) lymph nodes. At experienced centres, complication rates were 15.6% (9.4– 25.7), including 2% (0–5) retrograde ejaculation and 1.7% (0–6) reintervention. Operating room times are longer compared to O-RPLND (204 vs 186 min). Five publications with a follow-up of 63 (36–89) mo include 557 patients. One hundred twenty-six of 140 (90%) patients with positive nodes (25%, range: 17–38) received adjuvant chemotherapy, resulting in a local relapse rate of 1.4% (0.7–2.3) with no in-field recurrence; rate of distant relapses was 3.3% (1.8– 4.6), including one port-site metastasis; and rate of biochemical failure was 0.9% (0.7–2.3). Two of 14 patients with positive nodes (pN1) who did not receive adjuvant chemotherapy relapsed, both 8 mo after surgery, and were salvaged by chemotherapy. Compared with O-RPLND, there was no difference in relapse rates, percentage of patients receiving chemotherapy (29% vs 31%), chemotherapy (CTx) cycles per cohort (0.6), rate of salvage surgery (1.2% vs 1.5%), and patients with no evidence of disease (NED; 100% vs 99.7%). Conclusions: L-RPLND offers similar staging accuracy and long-term outcome to O-RPLND. In a late series of experienced L-RPLND centres, there was a trend towards fewer complications. L-RPLND represents a valuable tool for experienced laparoscopic surgeons. Further studies must focus on the curative potential of the procedure in pathologic stage IIA.

Keywords: Testis cancer Nonseminomatous germ cell cancer Retroperitoneal lymphadenectomy Laparoscopy Surveillance

# 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved.

* Corresponding author. Department of Urology, University of Heidelberg, Am Gesundbrunnen 20, D-74078 Heilbronn, Germany. Tel. +49 7131 492400; Fax: +49 7131 492429. E-mail address: [email protected] (J.J. Rassweiler). 0302-2838/$ – see back matter # 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved.

doi:10.1016/j.eururo.2008.08.022

european urology 54 (2008) 1004–1019

1.

Introduction

Of all clinical stage I nonseminomatous germ cell tumours (NSGCT), 20–30% have already metastasized into retroperitoneal lymph nodes but are not detectable by imaging techniques. Retroperitoneal lymph node dissection (RPLND) has been applied widely to detect metastases [1,2]. However, owing to the effectiveness of platinum-based chemotherapy (CTx), the role of RPLND has decreased within past years [3–6]. Recently, the European Germ Cell Cancer Consensus Group (EGCCCG) has recommended a risk-adapted approach [5], which is also reflected in the 2008 European Association of Urology (EAU) guidelines [6]. Initially, the percentage of embryonal carcinoma was considered a risk factor for the presence of lymph node metastases [7]; actually, only peritumoural vascular invasion is regarded as a risk factor. Such high-risk patients should receive two cycles of platinum-based CTx. Low-risk patients are subjected to surveillance [8]. Open RPLND (O-RPLND) is the second option in both cases. The EAU guidelines use the following description of the role of laparoscopic RPLND (L-RPLND): ‘‘It may become a good alternative to an open staging RPLND, but currently cannot be recommended as a standard diagnostic tool.’’ We felt that an evaluation of the current results of L-RPLND may improve the body of evidence. To minimize any existing bias in favour of laparoscopy, the team of authors includes two experts in O-RPLND, both members of the EAU guideline committee. 2.

Methods

2.1.

Literature search

A systematic search of the literature using the terms testis tumour, laparoscopic retroperitoneal lymph node dissection, low stage, complications, surveillance, and chemotherapy was performed in Medline, EMBASE, and Cochrane. The inclusion criteria were randomized controlled trials (RCT) or observational series of good quality. The largest series from each group of authors was included when fulfilling the abovementioned criteria. Previous series from the same group were taken only if they provided additional information. Primary outcome parameters were disease-free survival and relapse rate. Secondary outcome parameters included perioperative morbidity and long-term complications classified according to the Clavien system [9].

2.2. Meta-analysis to compare laparoscopic with open retroperitoneal lymph node dissection For comparison of O-RPLND and L-RPLND, only articles published in the year 2000 or later were considered. The summarised data were calculated based on the raw data of

1005

each article. For statistical analysis of continuous variables, student t test or Wilcoxon rank sum test was used. Categorical variables were compared using the Person x2 and Fisher exact tests. A p value <0.05 was determined as statistically significant.

2.2.1.

Comparison of operative outcome

To compare the perioperative outcome of L-RPLND with O-RPLND, we have selected the five largest contemporary L-RPLND-series, reporting on 449 patients [10–14], versus the results of four European and North American (n = 524) open series [15–18] (Table 2).

2.2.2.

Comparison of oncologic outcome

Long-term oncologic data provided by five (n = 557) international L-RPLND-series [11,13,14,19,20] were compared to five (n = 761) and to three (n = 513) international O-RPLND series [7,16,17,21,22], respectively, focusing on rate and site of relapse and on incidence and amount of CTx as well as on disease-free survival (Tables 3 and 5).

2.3.

Comparative studies

The results of four single-centre studies retrospectively comparing L-RPLND with O-RPLND [23–26] were analyzed (Table 4).

3.

Results

3.1.

Historic aspects

In 1992, Hulbert and Fraley reported the first case of L-RPLND [27]. Two years later, Klotz [28] presented a series of four patients, and Gerber et al [29] pooled the early experience of five institutions in North America. Based on animal studies, Janetschek et al [30] presented the first larger single-centre series. Table 1 summarizes the results of all subsequent early studies worldwide, including 179 patients [29– 40]. Further innovative presentations focused on an extra- or retroperitoneal approach [35,41,42]; an infrared ureteral stent [43]; the description of the nerve-sparing technique [44], especially using a water-jet dissector [45]; the use of intraoperative radio-guided sentinel lymph node mapping [46]; and hand-assisted [47] or even robot-assisted [48] techniques. After >15 yr, the results of >800 patients have been reported. 3.2.

Technical aspects

3.2.1.

Different modified template

All laparoscopic groups performed a modified RPLND with en bloc resection of lymphatic tissue following the recommendations for open surgery [49–51]. Eggener et al [51] recently elaborated on the differences of these templates.

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european urology 54 (2008) 1004–1019

Table 1 – Operative data from an initial series of laparoscopic retroperitoneal lymph node dissection for stage I disease Author

n

Gerber [29], 1994 (United States) Janetschek [30], 1994 (Innsbruck, Austria) Rassweiler [31], 1996 (Mannheim/ Heilbronn, Germany) Bianchi [32], 1998 (Verona, Italy) Zhuo [33], 1998 (Berlin, Germany) Nelson [34], 1999 (Baltimore, MD, USA) LeBlanc [35], 2001 (Lille/Lyon, France) Yang [36], 2003 (Shenzhen, China) Porter [37], 2003 (Seattle, WA, USA) Matsunuma [38], 2003 (Nagoya, Japan) Tobias-Machado [39], 2004 (Sao Paolo, Brazil) Corvin [40], 2004 (Tuebingen, Germany) Range

20 15

480 480

30 46.7

10 13.3

17

294

23.5

6 13 29 20 9 24 3 5

325 292 258 240 260 294 204 200

18 7.7 13.8 – – 12.5 – 20

18 179

OR time Complication Conversion Reintervention Hospital Positive (minutes) (%) (%) (%) stay (days) nodes (%)

232 200–480

5.6 5.6–46.7

5 –

3 5.5

17 20

5.8

5.8

4.5

5.8

– 7.7 6.9 – – – – –

– – – – – – – –

4.8 6.4 2.6 1.2 5.5 2.1 N/A 3

33 – 41 30 – 62.5 – 40

– 5.8–13.3

– 5–5.8

N/A 1.2–6.4

38.9 5.8–62.5

OR = operating room; N/A = not available.

European and South American L-RPLND centres [10,11,13,14,25,30–32,40,41] followed the template of Weissbach et al [49], including on the left side the upper preaortic (field 4, above the inferior mesenteric artery) and para-aortic (fields 5 + 10) nodes and on the right side the paracaval (fields 1 + 6), precaval (fields 2 + 7), interaortocaval (fields 3 + 8), upper preaortic (field 4), and right iliac (field 11) nodes. Left iliac (field 12) and suprahilar nodes (field 15) were not included (Fig. 1). Recently, two L-RPLND centres included the left iliac group (field 12) in the template [11,19].

North American L-RPLND centres [20,29,34,37] performed the dissection as proposed by Donohue and Foster [50], including on the left side the upper interaortocaval (field 3), left para-aortic (fields 5 + 10), and left iliac (field 12) groups and on the right side the paracaval (fields 1 + 6), precaval (fields 2 + 7), interaortocaval (fields 3 + 8), and right iliac (field 11) groups but not the preaortic (field 4) group. Recently, one L-RPLND centre reported to extend the dissection on the contralateral side if positive lymph nodes are found [52].

Fig. 1 – Modified templates of laparoscopic retroperitoneal lymph node dissection (L-RPLND) with percentage and site of pN+ in Weissbach study [49], including the definition and numbers of fields. GT = site of growing teratoma (n = 1) in the Cresswell study [14]; Rec = sites of recurrent metastasis following pN0 at L-RPLND.

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european urology 54 (2008) 1004–1019

A unilateral or bilateral nerve-sparing technique with preservation of the sympathetic fibres and ganglia within the template as proposed by Jewett [53] has been described laparoscopically by Peschel et al [44] but has not yet become a routine procedure. 3.2.2.

Operative technique

Under general anaesthesia, the patient is placed in a lateral oblique/flank position on the relevant side. The dissection can be performed through a trans- or retroperitoneal access. Important landmarks include the adequate exposure of the vena cava and/or the aorta, the renal vein(s), and the ureter. Capture of the resected nodal tissue is facilitated by use of a small-sized, self-opening organ bag because of the malignant potential of the lymphatic tissue. 3.3.

abstract) reported on port-site metastases [10,14,54]. Twenty-six articles were excluded because of significantly overlapping results from the same authors or presenting reviews of L-RPLND. There were no RCTs published concerning L-RPLND and only two analyzing the role of O-RPLND [22,55].

Selection of articles

Since 1992, we identified 60 articles reporting on >800 patients with clinical stage I NSGCT who underwent L-RPLND. Twenty-two papers were of historical interest or reported on technical details [27–48,52]. Seven articles focused on perioperative and long-term oncologic results [10–14,19,20]; four retrospective series compared O-RPLND and L-RPLND [23–26]. Three papers (one only as an

3.4. Evaluation of laparoscopic retroperitoneal lymph node dissection 3.4.1.

Operative data

In early series (n = 191), the conversion rate ranged between 5.8% and 13.3%, mainly because of uncontrollable bleeding from injury to larger vessels, whereas in recent publications, the conversion rate dropped to 3.3% (range: 1.1–5.4%; Tables 1 and 2). Accordingly, the mean operating time of the procedure decreased significantly from 258–480 min to 204 min (range: 138–261 min). Nineteen (3.8%) patients underwent an abbreviated dissection because of positive lymph nodes found on frozen section [34,41]. Initially, the rate of positive lymph nodes varied unacceptably (5.8–62.5%), but in the last six recent series (n = 557), the rate was 25% (range: 18–38; Table 3). Only three contemporary studies recorded the number of removed lymph nodes with a mean of 16 (range: 14–20) nodes [14,19,20].

Table 2 – Operative data from later series (2000–2008) of laparoscopic and open retroperitoneal lymph node dissection for stage I disease Author Laparoscopy Castillo [10], 2004 (Santiago, Chile) Albqami [1], 2005 (Linz, Austria) Romero [12], 2006 (Baltimore, MD, USA) Neyer [13], 2007 (Innsbruck, Austria) Cresswell [14], 2008 (Heilbronn, Germany) Total Open surgery Weissbach [15], 2000 Spermon [16], 2002 (The Netherlands) Heidenreich [17], 2003 (Germany) Beck [18], 2007 (Indianapolis, IN, USA) Total

n

OR time (minutes)

Complication (%)

Conversion (%)

Reintervention (%)

Hospital stay (days)

No. of nodes

96

138

14.6

4.2

1.0

1.8

14 (5–36)

103

217

11.6

2.9

0

3.6

N/A

77

N/A

10.8

5.4

0

2.0

N/A

136

261

25.7

5.1

0.7

4.1

N/A

87

177

9.4

1.1

5.7

5.0

14 (4–25)

499

204

15.6

3.8

1.4

3.3

14

109 101

N/A 158

41.0 40.0

N/A N/A

0 13.0

N/A 6.0

N/A N/A

239

214

34.2

N/A

8.9

8.0

18.5 (9–57)

75

132

16.1*

N/A

0

2.8

N/A

524

186

33

N/A

6.6

6.6

19

OR = operating room; N/A = not available. No data on retrograde ejaculation (no nerve-sparing in 6.7%).

*

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european urology 54 (2008) 1004–1019

Table 3 – Long-term oncologic data from later series (2000–2008) of laparoscopic and open retroperitoneal lymph node dissection for stage I disease Author

Laparoscopy Albqami [11], 2005 (Linz, Austria) Neyer [13], 2007 (Innsbruck, Austria) Castillo [19], 2007 (Santiago, Chile) Nielsen [20], 2007 (United States) Cresswell [14], 2008 (Heilbronn, Germany) Total Open surgery Spermon [16], 2002 (The Netherlands) Heidenreich [17], 2003 (Germany) Stephenson [21], 2005 (Memorial Sloan-Kettering Cancer Center, USA) Al-Tourah [7], 2005 (Canada) Albers [22], 2008 (Germany) Total

n

Positive Retroperitoneal In-field Distant Biochemical Secondary Follow-up nodes (%) relapse (%) relapse (%) relapse (%) failure (%) retroperitoneal (mo) surgery (%)

103

25

1.0

0

2.9

1.0

0

62

136

18

0.7

0

4.4

0.7

1.4

89

111

19

1.8

0

1.8

0.9

0

30

120

38

1.6

0

4.1

1.6

3.3

36

87

24

2.3

0

4.6

2.3

2.3

84

557

25

1.4

0

3.3

0.9

1.1

63

101

31

0

0

8.9

0

0

83

239

28

1.3

0.8

4.2

1.2

0.8

44

196

34*

1.5

0.45

4.5

N/A

3.1

53

52

40*

0

0

7.6

0

1.9

48

173

18.5

2.8

0.6

4.6

3.4

1.2

56

761

28.5

1.3

0.45

6.1

1.1

1.5

54

N/A = not available. Only patients with predominant embryonal carcinoma and/or lymphovascular invasion.

*

3.4.2.

Complications

Complication rates (Tables 1 and 2) varied between 5.6% and 46.7% in early series, decreasing to 15.6% (range: 9.4–25.7%) in later publications. Major intraoperative complications (Clavien III–IV) included bleeding as well as ureteral, duodenal, and gall bladder injury. With increasing experience, the majority of complications could be managed laparoscopically, which is reflected by the low conversion rates (3.7%; range: 1–5.4%) of recent series. Early postoperative complications were lymphoceles, pulmonary embolism, myonecrosis, leg paraesthesia, pressure sore, emphysema, one pseudomembranous colitis, and paralytic ileus. Most of these complications were related to the learning curve associated with long operating time. Late complications consisted of ureteral strictures and retrograde ejaculation in 2–3%, but there were three reports of port-site metastases (0.3%) in the literature [10,14,54], which had not occurred after O-RPLND. In Heilbronn [14], the pathologic slides of all 12 lymph nodes were reviewed, revealing no tumour. For entrapment of the speci-

men, only a retractor sheath was used. All three patients were salvaged by resection of the metastasis plus CTx. The reintervention rate in later series was 1.4% (range: 0–5.7%), predominantly including temporary double-J stent placement or percutaneous lymphocele drainage (Table 2). There was no change of length of postoperative hospital stay when comparing early and late studies (range: 1.2– 6.4 d), mainly related to the different health systems. 3.4.3.

Oncologic long-term follow-up

One hundred forty (25%) of the 557 men of the five long-term series had positive lymph nodes, and 126 underwent adjuvant CTx (ie, two to three cycles of polychemotherapy with cisplatin, etoposide, and bleomycin [PEB]). The retroperitoneal relapse rate was 1.4% (range: 0.7–2.3%), with no in-field recurrences according to the respective templates (Fig. 1). Distant metastases (predominantly pulmonary) occurred in 3.3% (range: 1.6–4.6%) and biochemical relapse alone occurred in 0.9% (range: 0–2.3%). This cohort included only a single port-site metastasis (0.2%). One hundred sixty-one (29%) patients were

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european urology 54 (2008) 1004–1019

Table 4 – Comparative studies of laparoscopic versus open retroperitoneal lymph node dissection: operative data Author

n

Macedo [50], 1994 Laparoscopic Open Janetschek [51], 1996 Laparoscopic Open Poulakis [52], 2006 Laparoscopic Open Abdel-Aziz [53], 2006 Laparoscopic Open

27 14 13 59 29 30 50 21 29 28 22 6

OR time Complication Reintervention Analgesics Hospital Positive (minutes) (%) (%) (hours) stay (days) nodes (%) 288 309

N/A N/A

7.1 7.7

24 72

5.5 12.4

N/A N/A

390 252

41.4 30

– 3.3

36 72

4.7 10,6

27.6 16.7

233 203

15.0 86.2

4.8 6.9

8 30

2 7

19 24

313 284

22.8 16.7

– –

N/A N/A

1.2 8.5

32 –

Comments Antegrade ejaculation open vs laparoscopic (86% vs 93%) Steep learning curve of L-RPLND Learning curve of L-RPLND decreases OR time More lymph nodes removed by O-RPLND (33 vs 17)

OR = operating room; N/A = not available; L-RPLND = laparascopic retroperitoneal lymph node dissection; O-RPLND = open retroperitoneal lymph node dissection.

treated either by adjuvant (n = 126) or salvage (n = 35) CTx, resulting in a mean of 0.6 (range: 0.4–0.8) cycles. Of the 14 patients with positive nodes (pN1) who did not receive adjuvant CTx [39,40,47], 2 patients relapsed, both 8 mo after surgery (one biochemical recurrence, one chest recurrence), and were salvaged by three and four cycles, respectively, of platinum-based CTx. Six of 557 patients (1.1%) required secondary surgical removal of retroperitoneal residual tumour following salvage CTx for retroperitoneal relapse, which revealed a mature teratoma in 4 patients and

necrotic tissue in 2 patients. Following a mean observation time of 63 mo (range: 36–89 mo), all patients had no evidence of disease (NED). 3.5. Comparison with open retroperitoneal lymph node dissection 3.5.1.

Comparative studies

There are only four comparative studies (Table 4) in the literature: two early series and two late series. Even in the late studies, L-RPLND was associated with longer operating time (30 min more) but

Table 5 – Long-term comparison of later series (2000–2008) of laparoscopic and open retroperitoneal lymph node dissection: frequency and amount of chemotherapy Author

n

Positive nodes n (%)

Retroperitoneal relapse (%)

Distant relapse/ biochemical failure (%)

Chemotherapy n (%)

No. of cycles per cohort

NED (%)

103

26 (25)

1.0

3.9

32 (31)

0.6

100

Laparoscopy Albqami [11], 2005 (Linz, Austria) Neyer [13], 2007 (Innsbruck, Austria) Castillo [19], 2007 (Santiago, Chile) Nielsen [20], 2007 (United States) Cresswell [14], 2008 (Heilbronn, Germany)

136

25 (18)

0.7

5.2

33 (24)

0.5

100

111

21 (19)

1.8

2.7

24 (22)

0.4

100

120

46 (38)

1.6

4.1

45 (38)

0.8

100

87

22 (25)

2.3

6.9

27 (31)

0.7

100

Total

557

140 (25)

1.4

4.2

161 (29)

0.6

100

101

31 (31)

0

8.9

38 (38)

0.9

98

239

67 (28)

1.3

5.4

74 (31)

0.7

100

173

32 (18)

2.9

4.6

45 (26)

0.5

100

513

130 (25)

1.6

6.6

157 (31)

0.6

Spermon [16], 2002 (The Netherlands) Heidenreich [17], 2003 (Germany) Albers [22], 2008 (Germany) Total NED, no evidence of disease.

99.6

1010

european urology 54 (2008) 1004–1019

required less analgesic (33–50% of dose) and a shorter hospital stay (4–7 d less). The data on complication rates and positive nodes were divergent. The relatively high complication rate following O-RPLND (86% vs 15%) in the study of Poulakis et al [25] was mainly related to minor postoperative complications such as fever (24% vs 5%), prolonged paralytic ileus (5% vs 20%), and wound problems (0% vs 20%). One group reported removal of more lymph nodes by open surgery [26]. Because of the immature design of all four studies (ie, small number, retrospective), the evidence level is only IV/C.

choice for diagnosis and therapy of stage I NSGCT, a risk-adapted strategy of surveillance and adjuvant CTx have become the preferred options [5,6]. L-RPLND was advocated as a compromise, offering minimally invasive lymph node staging, increasing the safety of any surveillance strategy, and avoiding overtreatment with adjuvant CTx [30,31,41]. Several critiques, however, have been mentioned: (1) insufficient template of dissection, (2) no nerve-sparing technique, (3) only a diagnostic and not therapeutic procedure, and (4) morbidity because of the learning curve.

3.5.2.

4.1. The template of laparoscopic retroperitoneal lymph node dissection

Meta-analysis of recent larger series

Concerning the operative data, we found a significantly longer operating time (204 vs 186 min; p < 0.05) for L-RPLND (n = 499) compared to O-RPLND (n = 524; Tables 3 and 5); however, complication rate (15.6% vs 33%; p < 0.05), reintervention rate (1.4% vs 6.6%; p < 0.05), and hospital stay (3.3 vs 6.6 d; p < 0.05) favoured L-RPLND. The oncologic data (Table 5) of five recent laparoscopic series (n = 557) compared with five open series (n = 761) were almost identical with respect to retroperitoneal relapse (1.3% vs 1.4%), infield relapse (0% vs 0.45%), distant progression (3.3% vs 6.1%), and biochemical failure (0.9% vs 1.1%), but the rate of positive lymph nodes was higher after ORPLND (25% vs 28.%). If, however, one excludes the two series presenting data with predominance of embryonal cell carcinoma and/or lymphovascular invasion [7,49], the figures change: 140 of 557 LRPLND-patients (25%) had positive nodes compared to 130 of 513 O-RPLND patients (25%). Moreover, the rates of patients receiving CTx were similar (29% vs 31%), resulting in an identical number of 0.6 cycles administered per cohort. The need for secondary retroperitoneal surgery also did not differ (1.1% vs 1.5%). Accordingly, both groups yielded similar cure rates (100% vs 99.6% NED). In summary, at centres of expertise, L-RPLND requires a slightly longer operating time, provides a lower overall rate of complications (including reinterventions), yields a similar rate of positive nodes, and provides similar oncologic outcomes with the same numbers of chemotherapeutic cycles per cohort compared to O-RPLND (evidence level III/B).

4.

Discussion

The management of clinical stage I NSGCT has undergone significant changes during the past decade. Whereas O-RPLND represented the first

Is the template of L-RPLND accurate enough to state that there is no need for adjuvant CTx when the node status is found to be negative [51]? Basically, this corresponds to the incidence of in-field recurrences following L-RPLND. In 557 patients, no infield relapse occurred, reflecting the diagnostic accuracy of the procedure. Moreover, excluding selective open series with predominant embryonal carcinoma and/or lymphovascular invasion [7,21,56], the rate of detected lymph node metastases averaged 25% in both groups. Retroperitoneal relapse outside the template was observed in 1.2% (range: 0.7–2.3%) of these series (Fig. 1). Any relapse outside the template may indicate that an inadequate template was performed in those cases [51]. Obviously, modified templates may differ in Europe and the United States, but this also concerns O-RPLND [49,50]. In the Heilbronn series, one leftsided recurrence occurred at the level of the left iliac group (field 15); therefore, we have extended the left-sided template [50]. The rate of retroperitoneal out-field relapse is identical when comparing L-RPLND and O-RPLND (1.4% vs 1.3%). These figures are lower than in the original Weissbach study [49] (Fig. 1), with 6% left and 3% right lymph node metastases outside the template. Any modified template represents a compromise in detecting all positive nodes and in preserving antegrade ejaculation. In this scenario, a 1.4% retroperitoneal relapse rate seems to be acceptable. Extension of dissection (ie, bilateral) may only be indicated in case of evident metastatic nodes within the modified template. In this situation, a nervesparing technique, as described by Peschel [44], should be performed. Among the authors, there is consensus that a routine bilateral L-RPLND or O-RPLND would represent a significant overtreatment with minimal benefit for the patient in this low stage.

european urology 54 (2008) 1004–1019

4.2. Nerve-sparing technique versus modified en bloc resection

There have been two different approaches minimizing the rate of retrograde ejaculation following RPLND. Weissbach et al presented the results of a multicentre study to determine the localization of solitary and multiple lymph node metastases (Fig. 1) as a basis for a modified lymphadenectomy [49]. At the same time, Jewett and colleagues published the technique of preserving the postganglionic sympathetic nerves beside the aorta to ensure antegrade ejaculation [53]. Colleselli et al [57] significantly influenced the laparoscopic approach, demonstrating in the cadaver that the L2 and L3 ganglia are close to each other and are often fused. Consecutively, antegrade ejaculation should still be present if the contralateral ganglia and postganglionic fibres below the inferior mesenteric artery are preserved. This is in favour of a template-based en bloc resection of the lymph node chains without the absolute need of nerve preservation. The high rates of antegrade ejaculation yielding 97–100% in contemporary L-RPLND series reflect the relevance of the Colleselli study [57]. It may be difficult to understand why the use of carbon dioxide insufflation and a laparoscopic en bloc dissection technique may be superior compared with previous open studies using a modified template (0–2% vs 7–14%) or even a nerve-sparing dissection with 2–6% loss of ejaculation [16,17,50,53,56]. This difference could be related to a less-extended dissection and/or the learning curve of the nerve-sparing technique. Among the authors, there is consensus that the rate of retrograde ejaculation following RPLND should be minimized. This can be achieved either by a nerve-sparing technique or using a modified template without any deterioration of the oncologic outcome. In the selected cases of a bilateral RPLND, the nerve-sparing technique may become mandatory [58]. 4.3. The therapeutic impact of laparoscopic retroperitoneal lymph node dissection

The most frequent concern about L-RPLND focuses on the therapeutic impact of the procedure (ie, avoiding CTx). Based on the RCT of Williams et al [55], adjuvant CTx in case of pathological stage II has been already applied in Europe before the introduction of L-RPLND and represents a grade A recommendation in EAU guidelines [6]. Laparoscopic centres adopted the same strategy but not for compensation of any diagnostic or therapeutic insufficiency.

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Advocates of O-RPLND emphasize that the relapse rate in case of pN+ status without adjuvant CTx ranges from 30% to 50% depending on the number and histologic pattern of involved lymph nodes and elevated markers prior to RPLND [56,59]. Laparoscopic centres always excluded patients with elevated markers after orchiectomy based on halflive kinetics. Several European centres have also used O-RPLND therapeutically in low-volume disease (ie, stage IIA, pN1). In the German Testicular Cancer Study Group, 14% of stage IIA patients had been subjected to surveillance after RPLND [17]. The therapeutic impact of L-RPLND has been tested recently in 10 lymph node–positive patients, showing a comparable relapse rate of 20% [20]. The concept of RPLND with curative intent should reduce the rate and number of chemotherapeutic cycles in the treated population. Based on the article of Stephenson and colleagues [21], we calculated the estimated CTx requirements in laparoscopic and open RPLND series. Selecting a high-risk population (41% pN+), 31% of their patients received CTx amounting to 0.8 cycles per cohort. Excluding such selected series [7,21], we were not able to detect any significant differences between L-RPLND and O-RPLND: The percentage of patients receiving CTx because of the adjuvant concept (ie, stage II), relapse in case of negative nodes (ie, stage I), or delayed relapse following surveillance was similar (29% vs 31%), and the calculated average of chemotherapeutic cycles per cohort was 0.6 in both groups. Such calculations may be biased by selection criteria for RPLND (ie, the proportion of high-risk patients) and trends to minimize the numbers of chemotherapeutic cycles (ie, two versus three) or rate of stage IIA patients under surveillance (ie, only pN1). Similar calculations, however, should be considered for future clinical studies. Based on the results of Albers et al [22], such a study could focus on the role of L-RPLND without or in combination with a single cycle of PEB. The consensus of the authors is that the curative option of L-RPLND in low-volume stage IIA (pN+) should be further studied (ie, international study), but the value of this concept in case of stage IIB disease remains uncertain. 4.4. The learning curve of retroperitoneal lymph node dissection

RPLND is challenging, whether it is performed laparoscopically or by open surgery. The expertise of the surgeon has a major impact on the outcome and morbidity of the procedure, as demonstrated for O-RPLND by the German Testicular Cancer Study

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Group [17]: The complication rate for surgeons with >20 cases varied between 8–29% compared with 25–50% if fewer than seven cases were performed. Accordingly, the complication rate of the early L-RPLND series varied between 5.6–46.7% compared with 9.4–25.7% in contemporary publications. Because of the limited number of L-RPLND centres, surgical expertise was concentrated, and the learning curves levelled off as reflected by the shorter operating room times, which, however, still differ slightly from the open series (204 vs 186 min). The observation of port-site metastases is unique to the laparoscopic approach, occurring after staging [10,14,54] and post-CTx L-RPLND [60,61], but it is rare (0.2%) and mainly related to the learning curve [60,61]. As long as L-RPLND remains a selected procedure for dedicated centres of expertise, the learning curve may not play an important role in the future. The consensus of the authors is that O-RPLND and L-RPLND represent technically challenging procedures and should be concentrated in dedicated referral centres. 4.5. Indications for laparoscopic retroperitoneal lymph node dissection

When considering the 2008 EAU guidelines for testicular tumours [5,6], it is obvious that the role of RPLND has diminished significantly. This study shows that at experienced centres, L-RPLND with adjuvant CTx has a low morbidity and demonstrates equal oncologic control in clinical stage I NSGCT as compared to O-RPLND. Thus, L-RPLND might be indicated in low-risk stages (1) if surveillance is contraindicated (ie, poor compliance), (2) if the primary tumour predominantly contains mature teratoma, or (3) if the primary NSGCT is markernegative. The last two situations are associated with a high risk of retroperitoneal teratoma. In high-risk clinical stage I, L-RPLND might be indicated if there are any contraindications for primary CTx. These are the same indications as for O-RPLND. We could show that at experienced centres, the perioperative morbidity of L-RPLND is lower than its open counterpart (evidence level IIIA). One may argue that we compared multicentre O-RPLND studies also involving low-volume surgeons [15,17] to the results of L-RPLND-experts. However, all L-RPLND-studies include the learning curves. The question is whether the reduced access trauma of the laparoscopic approach in the presence of the low long-term morbidity of both surgical techniques has any impact on the spectrum of indications. This concerns the demands on surgical

staging as well as criteria for the nonsurgical strategies. Unlike in most other urologic malignancies, for NSGCT, the importance of surgical lymph node staging has continuously diminished. Is this only attributed to the associated morbidity of the open access? Surgical staging still leaves 5–10% of the patients with the risk of undetected distant metastases. Consecutively, any therapeutic option represents a compromise to reduce the morbidity of the treatment without increasing the risk of treatment failure. In this scenario, L-RPLND may offer similar diagnostic accuracy to O-RPLND with less perioperative morbidity (ie, postoperative pain, paralytic ileus, wound problems). Further studies have to prove the therapeutic efficacy in stage IIA/ pN+; however, the operation still remains challenging. Risk factors have been identified to define lowrisk and high-risk group of patients with a risk of 13% and 64%, respectively [58]. Apart from the reduced rate and intervals of follow-up examination, L-RPLND does not offer any advantages for the low-risk group, but in the presence of vascular invasion, the morbidity of adjuvant CTx versus L-RPLND has to be compared. In an early study, Janetschek [24] demonstrated that the quality of life after L-RPLND was superior to that after two or three cycles of PEB. Of course, in 2008, only two cycles of PEB are standard, but the patients with pN0 (34–50%) would definitively benefit from L-RPLND associated with a shorter rehabilitation period and morbidity. Furthermore, the results of the recent study of the German Testicular Cancer Study Group comparing O-RPLND with one cycle of adjuvant PEB may significantly diminish the role of RPLND for stage I NSGCT [22]. Based on a phase 3 multicentre study (evidence level IA), one course of PEB was superior to RPLND as adjuvant therapy with no relapse to PEB versus 4.6% distant metastases after O-RPLND. The short- and long-term morbidity of one cycle of PEB is not comparable to the morbidity of L-RPLND or even O-RPLND; however, the long-term relapse rates of this trial have to be awaited. Because of the design of the study using 1.0 versus 0.6 cycles per cohort, the short-term outcome in favour of the CTx arm can be anticipated. This concept includes overtreatment for the vast majority of patients with pathologic stage I but may underestimate the dosage of CTx for some patients with clinically undetected metastases. Among the authors, the consensus is that the role of O-RPLND and L-RPLND has diminished in the past because of risk-adapted management and the reduction of chemotherapeutic cycles. The indications are mainly focussed on tumours not respond-

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ing to CTx as well as contraindications for surveillance and CTx.

5.

Conclusions

This study demonstrates that L-RPLND offers similar staging accuracy and long-term outcome to O-RPLND. In late series of well-experienced centres, there was a trend towards fewer complications in L-RPLND. It represents a valuable tool for selected patients with clinical stage I NGSCT. Further studies have to focus on the curative potential of the procedure, particularly in a high-risk population, as well as on the role of post-CTx L-RPLND. Author contributions: Jens J. Rassweiler had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Rassweiler, Laguna, Heidenreich, Janetschek. Acquisition of data: Rassweiler, Scheitlin, Janetschek. Analysis and interpretation of data: Rassweiler, Heidenreich, Laguna, Janetschek. Drafting of the manuscript: Rassweiler, Scheitlin. Critical revision of the manuscript for important intellectual content: Rassweiler, Laguna, Heidenreich, Janetschek. Statistical analysis: Rassweiler. Obtaining funding: None. Administrative, technical, or material support: Scheitlin. Supervision: Rassweiler. Other (specify): None. Financial disclosures: I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None. Funding/Support and role of the sponsor: None.

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Editorial Comment on: Laparoscopic Retroperitoneal Lymph Node Dissection: Does It Still Have a Role in the Management of Clinical Stage I Nonseminomatous Testis Cancer? A European Perspective Paolo Fornara, M. Raschid Hoda Clinic for Urology and Kidney Transplantation Centre, University Medical School of Halle/Wittenberg, Halle, Germany [email protected] The present paper by Rassweiler et al is a review of the currently available literature on the evidence of laparoscopic retroperitoneal lymph node dissection (L-RPLND) in patients with clinical stage I nonseminomatous germ-cell tumour (NSGCT) [1]. A systematic search for randomised controlled trials or observational series was performed using three major medical literature databases, and results for >800 patients were analysed. The paper also contains a meta-analysis comparing L-RPLND with open retroperitoneal lymph node dissection (O-RPLND). Primary outcome parameters were disease-free survival and relapse rate. Secondary outcome parameters included perioperative mor-

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[54] Sebe P, Nouri M, Haab F, Doublet JD, Gattegno B, Thibault P. Metastasis to trocar after lymphadenectomy with retroperitoneal laparoscopy. Prog Urol 2001;11:307–9. [55] Williams SD, Stablein DM, Einhorn LH, et al. Immediate adjuvant treatment versus observation with treatment at relapse in pathological stage II testicular cancer. N Engl J Med 1987;317:1433–8. [56] Stephenson AJ, Bosl GJ, Motzer J, et al. Retroperitoneal lymph node dissection for nonseminomatous germ cell testicular cancer: impact of patient selection on outcome. J Clin Oncol 2005;23:2781–8. [57] Colleselli K, Poisel S, Schachtner W, Bartsch G. Nervepreserving bilateral retroperitoneal lymphadenectomy: anatomical study and operative approach. J Urol 1990; 144:293–8. [58] Albers P. Management of stage I testis cancer. Eur Urol 2007;51:34–44. [59] Rabbani F, Sheinfield J, Farivar-Mohensi H, et al. Lowvolume nodal metastases detected at retroperitoneal lymphadenectomy for testicular cancer: pattern and prognostic factors for relapse. J Clin Oncol 2001;17:2020–5. [60] Spermon JR, Witjes JA. The danger of postchemotherapy laparoscopic retroperitoneal lymph node dissection for nonseminomatous testicular cancer. J Endourol 2008; 22:1013–6. [61] Rassweiler J, Tsivian A, Kumar AV, et al. Oncological safety of laparoscopic surgery for urologic malignancy: experience with more than 1000 operations. J Urol 2003; 169:2072–5.

bidity and long-term complications. Despite longer operation room times, L-RPLND offered similar staging accuracy and long-term outcome to ORPLND. The postorchidectomy treatment for patients with clinical stage I NSGCT remains controversial because several therapeutic options, including surveillance, primary chemotherapy, and retroperitoneal lymph node dissection (RPLND), are available. The idea behind an adjuvant therapy after orchidectomy in low-risk patients is to treat possible occult metastasis, which could relapse if only surveillance is applied. Primary chemotherapy with a cisplatin, etoposide, and bleomycin (PEB) regimen has been proven to be as efficacious as O-RPLND. Both, however, are associated with side-effects or inherent morbidity of a large laparotomy incision. Due to the superior benefits of the minimally invasive nature of laparoscopic technique, L-RPLND has the potential to become the method of choice for patients requiring RPLND. The oncologic safety in terms of tumour control and the diagnostic accuracy of L-RPLND seem to be equal to the open procedure; however, the morbidity is significantly lower. Moreover, the functional and social convalescence and

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quality of life has been reported to be better in patients receiving L-RPLND [2,3]. As pointed out by Rassweiler et al [1], the current potential for L-RPLND as a diagnostic and/or therapeutic tool is in clinical stage I NSGCT for cases in which no surveillance or chemotherapy are favoured by the patients. Regarding the curative role of RPLND (open or laparoscopic) in clinical stage IIA disease with low volume and in postchemotherapy stage IIA and IIB, some data from small-sized trials are available [4,5]. To clarify this issue, multicentre randomised trials with larger patient groups and longer follow-up are necessary and strongly encouraged. The use of laparoscopy was one of the most important steps in the progress of medicine in the 20th century. Laparoscopic radical nephrectomy is now considered the new gold-standard surgical treatment for benign renal masses as well as for localised renal cell carcinoma [6,7]. For radical prostatectomy, the laparoscopic approach provides promising results, which makes it likely to become the method of choice in the management of organconfined prostate cancer in the near future [8]. Nevertheless, laparoscopic techniques are associated with a learning curve. Hence, whenever reporting on laparoscopic methods (ie, L-RPLND), the adequate experience of the performing surgeon as well as that of the institution should be considered. For this purpose, hospital and surgeon case-load calculations to achieve optimum clinical outcome, already known from other surgical procedures, should also be applied to urologic laparoscopic procedures. As long as a high level of clinical evidence is not given for L-RPLND, only centres with adequate minimum case-load volume should be legitimate to perform this procedure.

References

Editorial Comment on: Laparoscopic Retroperitoneal Lymph Node Dissection: Does It Still Have a Role in the Management of Clinical Stage I Nonseminomatous Testis Cancer? A European Perspective Peter Albers Du¨sseldorf University, Du¨sseldorf, Germany [email protected]

low-risk tumors (no vascular invasion) and chemotherapy for high-risk tumors [1]. In Canada, the options for this patient group include surveillance, even for patients with high-risk features, based on equal cancer-specific survival data of >98% [2]. In view of these management guidelines, the review of Rassweiler and colleagues [3] is important for this small subgroup of <10% of patients with NSGCT who (1) wish to be staged surgically; (2) have pure teratomatous tumors; and (3) are at high risk for recurrence, do not want to undergo surveillance, and have contraindications for chemotherapy. In these rare situations, the patient may choose between open and laparoscopic

Surgical staging in patients with clinical stage I nonseminomatous germ cell tumors (NSGCT) has become a rare recommendation. In Europe, the recommendation is for patients to undergo a risk-adapted treatment with surveillance for

[1] Rassweiler JJ, Scheitlin W, Heidenreich A, Laguna MP, Janetschek G. Laparoscopic retroperitoneal lymph node dissection: does it still have a role in the management of clinical stage I nonseminomatous testis cancer? A European perspective. Eur Urol 2008;54:1004–19. [2] Poulakis V, Skriapas K, De Vries R, et al. Quality of life after laparoscopic and open retroperitoneal lymph node dissection in clinical stage I nonseminomatous germ cell tumor: a comparison study. Urology 2006; 68:154–60. [3] Steiner H, Peschel R, Janetschek G, et al. Long-term results of laparoscopic retroperitoneal lymph node dissection: a single-center 10-year experience. Urology 2004;63:550–5. [4] Weissbach L, Bussar-Maatz R, Flechtner H, Pichlmeier U, Hartmann M, Keller L. RPLND or primary chemotherapy in clinical stage IIA/B nonseminomatous germ cell tumors? Results of a prospective multicenter trial including quality of life assessment. Eur Urol 2000;37:582–94. [5] Neyer M, Peschel R, Akkad T, et al. Long-term results of laparoscopic retroperitoneal lymph-node dissection for clinical stage I nonseminomatous germ-cell testicular cancer. J Endourol 2007;21:180–3. [6] Fornara P, Doehn C, Seyfarth M, Jocham D. Why is urological laparoscopy minimally invasive? Eur Urol 2000; 37:241–50. [7] Fornara P, Doehn C, Friedrich HJ, Jocham D. Nonrandomized comparison of open flank versus laparoscopic nephrectomy in 249 patients with benign renal disease. Eur Urol 2001;40:24–31. [8] Jurczok A, Zacharias M, Wagner S, Hamza A, Fornara P. Prospective non-randomized evaluation of four mediators of the systemic response after extraperitoneal laparoscopic and open retropubic radical prostatectomy. BJU Int 2007;99:1461–6.

DOI: 10.1016/j.eururo.2008.08.023 DOI of original article: 10.1016/j.eururo.2008.08.022

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surgery; however, in both cases, he will ask about the experience of the surgeon and the complication rates of the procedure. In a multicenter randomized trial, the relatively high in-field recurrence rate after open retroperitoneal lymph node dissection (RPLND) was not an expected result [4]. This finding contradicts RPLND data from single centers with high operative volume and further diminishes the role of RPLND in a community setting. In their review, the authors stress the importance of experienced centers for laparoscopy and compare operative data from high-volume laparoscopic centers to multicenter data on open surgery [3]. A well-accepted definition of an ‘‘experienced laparoscopic RPLND center,’’ however, is not available. In summary, this review [3] focuses on a minority of patients for whom laparascopic RPLND (L-RPLND) may be an option; however, not even high-risk patients would benefit from a double procedure of laparoscopic staging and chemotherapy for metastatic disease, as opposed to surveillance and chemotherapy for treatment of metastases. The clinical problem of overtreatment of curable patients is not solved with laparoscopy.

References

Editorial Comment on: Laparoscopic Retroperitoneal Lymph Node Dissection: Does It Still Have a Role in the Management of Clinical Stage I Nonseminomatous Testis Cancer? A European Perspective Giorgio Pizzocaro Urology Clinic 2nd, University of Milan, San Giuseppe Hospital, Milan, Italy [email protected]

the testis by comparing large, recent series of L-RPLND and O-RPLND. Risk factors were not considered. Table 2 in their paper demonstrates a minimal difference in operative time; a smaller number of removed nodes in L-RPLND (14 vs 19 in O-RPLND); and a shorter hospital stay (3.3 vs 6.6 d) for L-RPLND, even if the same short hospital stay has been recently reported in O-RPLND [3]. Interestingly, approximately 30% of patients in both groups received postoperative chemotherapy (Table 4 in the paper): This means that nearly all patients with positive nodes in both groups received adjuvant chemotherapy! Surgery followed by adjuvant chemotherapy can be considered overtreatment compared to surveillance in lowrisk patients and adjuvant chemotherapy in highrisk patients. It has been reported that after O-RPLND alone [4], relapses do occur in approximately 10% of pathological stage I patients and in 30% of pathological stage IIA (pN1) patients. To compare L-RPLND versus O-RPLND today, we need to stratify clinical stage I patients into good- and poor-risk categories. Good-risk patients could be randomised to O-RPLND versus L-RPLND without postoperative

Postorchiectomy treatment of clinical stage I nonseminomatous germ cell tumours (NSGCT) of the testis is controversial. The European Germ Cell Cancer Cooperative Group (EGCCCG) recommends surveillance for low-risk patients (no peritumoral vascular invasion; expected relapse rate of 14–22%) and two courses of regular bleomycin, etoposide, and cisplatin (BEP) in poor-risk patients (peritumoral vascular invasion present; expected relapse rate of 48%). Retroperitoneal lymph node dissection (RPLND) is considered an alternative option in both cases [1]. Rassweiler et al [2] try to demonstrate the equivalence of open RPLND (O-RPLND) and laparoscopic RPLND (L-RPLND) in clinical stage I NSGCT of

[1] Albers P, Albrecht W, Algaba F, et al. EAU guidelines on testicular cancer. Arnhem, the Netherlands: European Association of Urology; 2008 http://www.uroweb.org/ fileadmin/tx_eauguidelines/09%20Testicular%20Cancer. pdf. [2] Duran I, Sturgeon JF, Jewett MA, et al. Initial versus recent outcomes with a non–risk adapted surveillance policy in stage I non-seminomatous germ cell tumors (NSGCT). J Clin Oncol 2007;25(Suppl June 20), abstract 5021. [3] Rassweiler JJ, Scheitlin W, Heidenreich A, Laguna MP, Janetschek G. Laparoscopic retroperitoneal lymph node dissection: does it still have a role in the management of clinical stage I nonseminomatous testis cancer? A European perspective. Eur Urol 2008;54:1004–19. [4] Albers P, Siener R, Krege S, et al. One course of adjuvant PEB chemotherapy versus retroperitoneal lymph node dissection in patients with stage I non-seminomatous germ-cell tumors (NSGCT): results of the German Prospective Multicenter Trial (Association of Urological Oncology (AUO)/German Testicular Cancer Study Group). J Clin Oncol 2008;26(Suppl June 20):2966–72.

DOI: 10.1016/j.eururo.2008.08.024 DOI of original article: 10.1016/j.eururo.2008.08.022

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adjuvant chemotherapy, which would be given only at relapse. Poor-risk patients would not enter this trial; they can enter a confirmatory trial of adjuvant chemotherapy versus RPLND followed by chemotherapy at relapse [5].

References [1] Krege S, Beyer J, Souchou R, et al. European consensus conference on diagnosis and treatment of germ cell cancer: a report of the second meeting of the European Germ Cell Cancer Consensus Group (EGCCCG): part I. Eur Urol 2008;53:478–96. [2] Rassweiler JJ, Scheitlin W, Heidenreich A, Laguna MP, Janetschek G. Laparoscopic retroperitoneal lymph node dissection: does it still have a role in the management of

Editorial Comment on: Laparoscopic Retroperitoneal Lymph Node Dissection: Does It Still Have a Role in the Management of Clinical Stage I Nonseminomatous Testis Cancer? A European Perspective Nicolas Mottet Urology Department, Clinique Mutualiste, St Etienne, France [email protected] This review focuses on laparoscopic retroperitoneal lymph node dissection (L-RPLND) [1]. The results suggest that it is a reliable procedure in expert hands. Many aspects remain unclear, such as the claimed benefit of ejaculation preservation using laparoscopy (97% compared with 81% in open RPLND). It is difficult to believe that both en bloc procedures include the same templates. The role of two courses of chemotherapy only if pN1 after a full bilateral RPLND is also unclear (a bilateral L-RPLND appears to be performed as an exception). Surveillance avoids overtreatment for more than 70% of pN1 [2,3] but requires three courses of bleomycin, cisplatin, and etoposide (BEP) at relapse. The quality-of-life comparison between chemotherapy or RPLND is biased (reference 24 in the text): It should be focused on high risk only, comparing two courses of BEP and L-RPLND followed by possible chemotherapy. A procedure leading to a 14% complication rate and a 1.7% reintervention rate is not minimally invasive, and the long-term toxicity of two courses of BEP remains unknown.

clinical stage I nonseminomatous testis cancer? A European perspective. Eur Urol 2008;54:1004–19. [3] Beck SDV, Peterson MD, Bihrle R, et al. Short-term morbidity of primary lymph node dissection in a contemporary group of patients. J Urol 2008;178:504–6. [4] Donohue JP, Thornhill JA, Foster RS, et al. Stage I nonseminomatous germ-cell testicular cancer—management options and risk benefit consideration. World J Urol 1994;12:170–6. [5] Albers P, Siener R, Krege S, et al. Randomised phase III trial comparing retroperitoneal lymph node dissection (RPLND) with one course of bleomycin, etoposide, cisplatin (BEP) chemotherapy in patients with stage I nonseminomatous germ cell tumour patients (NSGCT) – updated results of AUO Trial 01/94. Eur Urol Suppl 2008;7:84. DOI: 10.1016/j.eururo.2008.08.025 DOI of original article: 10.1016/j.eururo.2008.08.022

The real question is not how but when is RPLND required. For low-risk patients, active surveillance is the standard of care. For patients unwilling to use this modality, RPLND must be performed. The presence of primary teratoma raises a question, as it might be protective against nodal involvement [4]. For patients with vascular invasion [5], RPLND constitutes overtreatment for up to 50% of patients. Up to 30% of high-risk patients will be pN+, possibly requiring two courses of BEP, and 10% of patients with pN0 will finally relapse, requiring at least three courses of BEP. This combined modality is not the less toxic approach. Laparoscopy does not change the surgical indications. It is an even more specialized procedure compared with open RPLND. The rarity of indication leads to the question of the learning curve, even in reference centers.

References [1] Rassweiler JJ, Scheitlin W, Heidenreich A, Laguna MP, Janetschek G. Laparoscopic retroperitoneal lymph node dissection: does it still have a role in the management of clinical stage I nonseminomatous testis cancer? A European perspective. Eur Urol 2008;54:1004–19. [2] Donohue JP, Thornhill JA, Foster RS, Bihrle R, Rowland RG, Einhorn LH. The role of retroperitoneal lymphadenectomy in clinical stage B testis cancer: the Indiana University experience (1965 to 1989). J Urol 1995;153:85–9. [3] Rabbani F, Sheinfeld J, Farivar-Mohseni H, et al. Lowvolume nodal metastases detected at retroperitoneal

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lymphadenectomy for testicular cancer: pattern and prognostic factors for relapse. J Clin Oncol 2001; 19:2020–5. [4] Alexandre J, Fizazi K, Mahe´ C, et al. Stage I non-seminomatous germ-cell tumours of the testis: identification of a subgroup of patients with a very low risk of relapse. Eur J Cancer 2001;37:576–82.

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[5] De Wit R, Fizazi K. Controversies in the management of clinical stage I testis cancer. J Clin Oncol 2006;24: 5482–92.

DOI: 10.1016/j.eururo.2008.08.026 DOI of original article: 10.1016/j.eururo.2008.08.022