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Review – Prostate Cancer

The Benefits and Harms of Different Extents of Lymph Node Dissection During Radical Prostatectomy for Prostate Cancer: A Systematic Review

By: Nicola Fossatia 1, Peter-Paul M. Willemseb 1, Roderick C.N. van den Berghc, Thomas Van den Broeckd, Cathy Yuhong Yuane, Erik Briersf, Joaquim Bellmuntg h, Michel Bollai, Philip Cornfordj, Maria De Santisk, Ekelechi MacPepplel, Ann M. Henrym, Malcolm D. Masonn, Vsevolod B. Matveevo, Henk G. van der Poelp, Theo H. van der Kwastq, Olivier Rouvièrer, Ivo G. Schootss t, Thomas Wiegelu, Thomas B. Lamv w, Nicolas Mottetx and Steven Joniaud

European Urology, February 2017

Published online: 09 February 2017

Keywords: Prostate cancer, Surgery, Lymph node dissection, Staging, Oncological outcome, Functional outcome, Complications, Systematic review

Abstract Full Text Full Text PDF (3,2 MB)

Abstract

Context

There is controversy regarding the therapeutic role of pelvic lymph node dissection (PLND) in patients undergoing radical prostatectomy for prostate cancer (PCa).

Objective

To systematically review the relevant literature assessing the relative benefits and harms of PLND for oncological and non-oncological outcomes in patients undergoing radical prostatectomy for PCa.

Evidence acquisition

MEDLINE, MEDLINE In-Process, Embase, and the Cochrane Central Register of Controlled Trials were searched up to December 2015. Comparative studies evaluating no PLND, limited, standard, and (super)-extended PLND that reported oncological and non-oncological outcomes were included. Risk-of-bias and confounding assessments were performed. A narrative synthesis was undertaken.

Evidence synthesis

Overall, 66 studies recruiting a total of 275,269 patients were included (44 full-text articles and 22 conference abstracts). Oncological outcomes were addressed by 29 studies, one of which was a randomized clinical trial (RCT). Non-oncological outcomes were addressed by 43 studies, three of which were RCTs. There were high risks of bias and confounding in most studies. Conflicting results emerged when comparing biochemical and clinical recurrence, while no significant differences were observed among groups for survival. Conversely, the majority of studies showed that the more extensive the PLND, the greater the adverse outcomes in terms of operating time, blood loss, length of stay, and postoperative complications. No significant differences were observed in terms of urinary continence and erectile function recovery.

Conclusions

Although representing the most accurate staging procedure, PLND and its extension are associated with worse intraoperative and perioperative outcomes, whereas a direct therapeutic effect is still not evident from the current literature. The current poor quality of evidence indicates the need for robust and adequately powered clinical trials.

Patient summary

Based on a comprehensive review of the literature, this article summarizes the benefits and harms of removing lymph nodes during surgery to remove the prostate because of PCa. Although the quality of the data from the studies was poor, the review suggests that lymph node removal may not have any direct benefit on cancer outcomes and may instead result in more complications. Nevertheless, the procedure remains justified because it enables accurate assessment of cancer spread.

Take Home Message

Although representing the most accurate staging procedure, pelvic lymph node dissection (PLND)—irrespective of the extent (limited/standard vs [super]extended PLND)—is associated with worse intraoperative and perioperative outcomes, whereas a direct therapeutic effect is still not evident from the current literature. The current poor quality of evidence indicates the need for robust and adequately powered clinical trials.

Keywords: Prostate cancer, Surgery, Lymph node dissection, Staging, Oncological outcome, Functional outcome, Complications, Systematic review.

1. Introduction

The current European Association of Urology (EAU) prostate cancer (PCa) guidelines recommend performing extended pelvic lymph node dissection (PLND) in high-risk and intermediate-risk patients when the estimated risk for positive lymph nodes exceeds 5% [1]. However, the therapeutic role of PLND during radical prostatectomy for the management of PCa remains controversial. There are reports suggesting that PLND results in improved pathological staging, and that extending the PLND template may increase its staging accuracy. Nevertheless, the oncological benefit of the procedure is still unclear [2].

Historically, the decision to perform PLND, and on how extensive it ought to be, has been left to the clinical judgment of the surgeon. The lack of clarity regarding the oncological benefit of performing PLND, and the lack of standardized definitions and terminologies regarding the PLND template, have led to a wide variety of “experience-based approaches” [3] and [4] which render any comparisons between them difficult and fraught with uncertainties. It is also unclear whether the PLND outcomes vary between different patient subgroups (ie, low- vs intermediate- vs high-risk localized disease). Furthermore, PLND may be associated with an increased risk of adverse events, morbidity, length of stay, and healthcare costs. However, the assertion that more extensive PLND leads to higher complication rates has not always been confirmed [5], [6], and [7].

The objective of this systematic review was to evaluate the benefits and harms of PLND, incorporating the comparison between PLND of differing extent (ie, no PLND, limited PLND, standard PLND, extended PLND, and super-extended PLND) during radical prostatectomy for PCa, and to identify which patients benefit most from PLND.

2. Evidence acquisition

2.1. Search strategy, selection of studies, and data extraction

The protocol for this review has been published (www.crd.york.ac.uk/PROSPERO; registration number CRD42015024848), and the search strategy is outlined in the Supplementary material. In brief, databases including MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were systematically searched. Only English language articles and studies published from January 1980 to December 2015 were included. The search was complemented by additional sources including the reference lists of included studies. Two reviewers (NF and PPW) screened all abstracts and full-text articles independently. Disagreement was resolved by discussion or by reference to an independent third party (TVdB and SJ). The review was commissioned and undertaken by the EAU Prostate Cancer Guideline Panel as part of its guideline update for 2017.

2.2. Types of study designs included

All comparative studies (ie, randomized clinical trials [RCTs] and nonrandomized comparative studies [NRCS]) with at least one experimental arm and one control arm were included. Studies with more than two arms were also included. Single-arm case series, case reports, commentaries, reviews, and editorial commentaries were excluded. Relevant systematic reviews were scrutinized for potentially relevant studies for inclusion. Studies available as non–full-text articles only (eg, conference abstracts) were eligible for inclusion.

2.3. Types of participants included

The study population was limited to men above the age of 18 yr with histologically proven T1–3 N0 M0 PCa according to the TNM staging system (all versions of the TNM staging system) and who were undergoing radical prostatectomy. Patients with cNx or cMx were accepted for low- and intermediate-risk localized disease. Men with localized disease were further stratified according to the D’Amico classification if data were available.

2.4. Types of interventions included

The interventions were PLND performed during radical prostatectomy, incorporating all approaches (including open, robotic, or laparoscopic) and the different extents. Owing to the expected heterogeneity in defining the extent of PLND across studies, for the purpose of standardization the extent of PLND was determined a priori based on discussion and consultation with a reference expert panel (EAU Prostate Cancer Guideline Panel) and was categorized as follows (Fig. 1): (1) no PLND; (2) limited PLND (lPLND), obturator nodes; (3) standard PLND (sPLND), obturator and external iliac nodes; (4) extended PLND (ePLND), obturator, external, and internal iliac nodes; (5) super-extended PLND (sePLND), ePLND plus common iliac, presacral, and/or other nodes; and (6) PLND extent undefined or unclassified. Studies reporting discrepant extents and definitions were reclassified according to the above definitions.

gr1

Fig. 1

Anatomical areas for the definition of the extent of dissection. I = obturator nodes; II = external iliac nodes; III = internal iliac nodes; IV = common iliac nodes; V = presacral nodes.

2.5. Type of outcome measures included

The primary outcomes were biochemical recurrence (BCR), clinical recurrence (ie, development of distant metastasis), cancer-specific survival, and overall survival. Secondary outcomes included adverse events or complications reported either as grade of severity (eg, Clavien) or individual rates, and intraoperative and postoperative outcomes including operative time, blood loss, blood transfusion, duration of hospital stay, 30-d readmission rate, 90-d mortality, and functional outcomes including urinary continence and erectile function recovery. Lastly, data regarding the median total number of lymph nodes retrieved and the total number of positive lymph nodes in relation to PLND extent were also extracted.

2.6. Assessment of risk of bias

The risk of bias (RoB) of RCTs was assessed using the standard Cochrane RoB assessment tool for RCTs, while the RoB for NRCS was assessed using the modified Cochrane tool that included additional items to assess confounding bias. This was a pragmatic approach informed by the methodological literature pertaining to assessing RoB in NRCS [8]. A list of important outcome-specific prognostic confounders was defined a priori by the EAU Prostate Cancer Guideline Panel: clinical stage, pathological stage, pathological Gleason score, and adjuvant treatment for oncological outcomes; and age, body mass index (BMI), performance status, and surgical route for non-oncological outcomes. The overall judgment regarding each confounder was based on whether it was measured, if it was balanced across groups, and whether any statistical adjustment was made.

2.7. Data analysis

A data extraction form was developed to collect information on study design, participant characteristics, characteristics of interventions, and outcome measures. Two reviewers (NF and PPW) independently extracted data relating to the pre-specified outcomes. Descriptive statistics were used to summarize baseline characteristics data. For time-to-event data (eg, survival analysis), estimates such as median survival or the percentage event-free (survival rate) at specific time points as reported by authors were extracted. Adjusted and unadjusted hazard ratios (HRs) to estimate the size of intervention differences were extracted if available. For categorical data, point estimates reported as proportion (%), risk ratio (RR), and odds ratio (OR) were extracted. For continuous outcomes, the mean difference (MD) and corresponding 95% confidence interval (CI) were extracted. For NRCS, a narrative synthesis of the data was planned. Where possible, dichotomous outcomes comparing the intervention effect were analyzed using RR with 95% CI. The mean and standard deviation were used to summarize continuous outcome data and were compared using MD and 95% CI.

To explore the potential impact of clinical heterogeneity on outcomes, subgroup and sensitivity analyses were planned for the following variables: age, prostate-specific antigen (PSA) level, and the type, schedule, and timing (early vs deferred) of androgen deprivation therapy.

3. Evidence synthesis

3.1. Quantity of evidence identified

The study selection process is outlined in a Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) flow diagram (Fig. 2). In total, 4377 records were identified through database searching, and 3840 were screened after removal of duplicates. Of these, 178 articles were eligible for full-text screening, and 139 conference abstracts were assessed for eligibility. Finally, 66 studies recruiting a total of 275 269 patients met the inclusion criteria (44 full-text papers and 22 conference abstracts, with each reporting on a separate study).

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Fig. 2

Study selection flow diagram according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines.

3.2. Characteristics of the studies included

Data were included from 66 studies, three of which were RCTs [9], [10], and [11], four were prospective NRCS [12], [13], [14], and [15], and the remainder were retrospective NRCS [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62], [63], [64], [65], [66], [67], [68], [69], [70], [71], [72], [73], and [74]. The baseline characteristics for all included studies addressing oncological and non-oncological outcomes are shown in Table 1 and Table 2, respectively. The template and extents of PLND performed in the included studies are summarized in Supplementary Table 1: the more extensive the PLND, the higher the rate of pN1 disease.

Table 1

Baseline characteristics for studies addressing oncological outcomes

Study ID, design, country, recruitment periodSurgical routeTreatmentNFollow-up (mo)Age (yr)Initial PSA (ng/ml)Biopsy
Gleason score
Clinical
T stage
Pathologic
T stage
Pathologic
Gleason score
Surgical margin statusNumber of lymph nodes dissectedNumber of positive lymph nodesOutcomes reported on
No PLND versus any PLND
Karl 2015, retrospective comparative, Germany,
1994–2013
Open: 87%
Lap: 8%
Robotic: 2%
Perineal: 3%
No PLND60848 [NR]64.9
[R: 42–78]
<4: 8%
(n = 43)
4–9.9: 53%
(n = 282)
10–19.9: 27%
(n = 142)
≥20: 12%
(n = 64)
NRNRpT3a: 100%≤6: 14%
(n = 77)
3 + 4: 56%
(n = 301)
4 + 3: 21%
(n = 112)
≥8: 9%
(n = 46)
R1: 100%NRNRBFFS
PLND
Gandaglia 2015, retrospective comparative, Italy/France/Germany, 2000–2013NRNo PLND171040 (32.2)64
[IQR: 59–68]
5.4
[IQR: 4.2–6.8]
NRT1c: 91.2%
(n = 1560)
T2: 8.8%
(n = 150)
NRNRNRNRNRBCR
PLND
Koo 2015, retrospective comparative, South Korea, 2005–2009Open: 29%
Robotic: 71%
No PLND327NRNRNRNRNRNRNRNRNRNRBFFS
PLND403
Boehm 2015, retrospective comparative, Germany, 1992–2011Open: 95%
Robotic: 5%
No PLND4884NR64 (59–67)NR≤6: 29.2%
(n = 3412)
3 + 4: 53.8%
(n = 6303)
4 + 3: 13.0%
(n = 1529)
≥8: 3.8
(n = 443)
NRpT2: 70%
(n = 8172)
pT3a: 20%
(n = 2327)
≥pT3b: 10%
(n = 1223)
NRNRNRNRBFFS,
MFS,
CSS
PLND6810
Chen 2015, retrospective comparative, GCS, USANRNo PLND1754153 [NR]NRNRNRNRNRNRNRNRNACSS
PLND265711.9%
Abdollah 2014, retrospective comparative, EAU, ItalyNRNo PLND1406NR65 (NR)
66 [R: 44–80]
NRNRNRNRNRNR15 (NR)
14 [R: 8–52]
NRBFFS
PLND
Liss 2013, retrospective comparative, Germany, 2007–2011Robotic: 100%No PLND207NR61 (6.9)
63 (6.8)
61 (7.2)
4.9 (4.0–6.5)
≤6: 93.5% (n = 188)
7: 4.5% (n = 9)
≥8: 2% (n = 4)
T1: 78.3% (n = 162)
T2: 21.7% (n = 45)
T3: 0% (n = 0)
T1: 92.3% (n = 191)
T2: 6.8% (n = 14)
T3: 1%
(n = 2)
NRNRNANABFFS
sPLND2316.1 (4.4–9.2)
≤6: 58.9% (n = 136)
7: 39.4% (n = 91)
≥8: 1.7% (n = 4)
T1: 58.9% (n = 136)
T2: 39.4% (n = 91)
T3: 1.7% (n = 4)
T1: 72.7% (n = 168)
T2: 26.4% (n = 61)
T3: 0.9% (n = 2)
18 [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], and [25]0.3% (n = 13)
ePLND548.5 (5.5–13.5)
≤6: 27.8% (n = 15)
7: 68.5% (n = 37)
≥8: 3.7% (n = 2)
T1: 27.8% (n = 15)
T2: 68.5% (n = 37)
T3: 3.7% (n = 2)
T1: 42.6% (n = 23)
T2: 55.6% (n = 30)
T3: 1.9% (n = 1)
20 [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], and [28]2% (n = 24)
Mitsuzuka 2013, retrospective comparative, Japan, 2000–2009Open: 100%No PLND75NR63 [NR]5.9 (NR)≤6: 45.3% (n = 34)
7: 48% (n = 36)
≥8: 6.7% (n = 5)
T1c: 90.7% (n = 68)
T2a: 9.3% (n = 9)
NRNRNRNRNABFFS
MFS
CSS
OS
PLND14767 [NR]6.4 (NR)≤6: 28.6% (n = 42)
7: 61.2%
(n = 90)
≥8: 10.2% (n = 15)
T1c: 70.1%
(n = 103)
T2a: 29.9%
(n = 44)
0.7% (n = 1)
Masuda 2013, retrospective comparative, Japan, 2000–2010Single-port surgery: 100% (MIES-RP)No PLND37949.8 (NR)65.8 (NR)8.4 (NR)NRNRT3a: 32.5% (n = 123)
T3b: 4.0% (n = 15)
NRR1: 25.3% (n = 96)NRNRBFFS
PLND
De Almeida Prado Costa, 2013, retrospective comparative, WCE, FranceLap: 73%
Robotic: 27%
No PLND2293NRNRNRNRNRNRNRNR3% (n = 21)NRBFFS
PLND
Chang 2013, retrospective comparative, AUA, CanadaOpen: 100%No PLND33550.7 mNRNRNRNRNRNRNRNRNRCSS
PLND335
Pokala 2013, retrospective comparative, AUA, USANRNo PLND75416NR61.4
[R: 26–75]
NRNRNRNRNRNRNRNRBFFS
CSS
PLND
Daimon 2012, retrospective comparative, Japan, 2002–2006Lap: 100%No PLND5469.4 [NR]65.2 (NR)6.37 (NR)5.3 (NR)NRNRNRNRNRNRBFFS
Limited8554.8 (NR)6.48 (NR)5.2 (NR)
Ost 2012, Retrospective comparative, Belgium/Italy, 1999–2008NRNo PLND4660
[6–136]
NRNRNRNRNRNRNR0NRBFFS, LFFS
ePLND17910 (1–40)
Ku 2011, retrospective comparative, Republic of South Korea, 1997–2009]Open: 88%
Lap: 2.5%
Robotic: 9.5%
No PLND883766.9 (6.0)15.8 (15.9)<7: 11.4% (n = 10)
7: 13.6% (n = 12)
8: 48.9% (n = 43)
9: 23.9% (n = 21)
10: 2.3% (n = 2)
<T2c = 86.4% (n = 76)
≥T2c: 13.6% (n = 12)
NR<7: 9.1% (n = 8)
7: 54.4% (n = 48)
8: 12.5% (n = 11)
9: 22.7% (n = 20)
10: 1.1% (n = 1)
R0: 54.5% (n = 48)
R + : 45% (n = 40)
NRNRBF
PLND11165.3 (6.9)21.5 (35.9)<7: 11.7% (n = 13)
7: 19.8% (n = 22)
8: 42.3% (n = 47)
9: 24.3% (n = 27)
10: 1.8% (n = 2)
<T2c: 89.2% (n = 99)
≥T2c: 10.8% (n = 12)
<7: 2.7% (n = 3)
7: 66.7% (n = 74)
8: 10.8% (n = 12)
9: 19.8% (n = 22)
10: 0% (n = 0)
R0: 54.1% (n = 60)
R + : 45.9% (n = 51)
Logan 2011, retrospective comparative, AUA, USANRPLND8874 mNRNRNRNRNRNRNRNRNRBCR
No PLND123
Porter 2010, retrospective comparative, USA, 1954–1994Open: 43%
Perineal: 57%
No PLND410139NRNRNRNRNRNRNRNRNRPCSM
PLND342
Weight 2008, retrospective comparative, USA, 1995–1999Open: 100%No PLND19688 [NR]>65: 74% (n = 146)≤4: 15% (n = 30)
4–10: 85% (n = 166)
NRNRT3a: 45% (n = 23)
T3b: 2%
(n = 1)
≤6: 60% (n = 117);
7: 40% (n = 79)
NRNANABFFS
PLND14094.5 [NR]>65: 76% (n = 107)≤4: 19% (n = 19)
4–10: 86% (n = 121)
T3a: 48% (n = 34)
T3b: 5%
(n = 4)
≤6: 54% (n = 76)
7: 46% (n = 64)
9
[IQR: 5–13]
NR
Berglund 2007, retrospective comparative, USA, 1995–2005NRNo PLND73231.9 (40.5)< 65: 74% (n = 540)
<4: 22% (n = 155)
4.1–10: 68% (n = 472)
10.1–20: 7% (n = 48)
>20: 2% (n = 16)
2–4: 4% (n = 29)
5–6: 81% (n = 583)
7: 14% (n = 100)
8–10: 1% (n = 4)
T1: 60% (n = 416)
T2: 39% (n = 268)
T3: 1% (n = 7)
T4: 0% (n = 0)
NRNRNRNANAFFS: free from BF or free from initiation of secondary treatment (ADT, adjuvant RT or salvage RT)
lPLND396149.5 (30.4)< 65: 67% (n = 2659)
<4: 14% (n = 514)
4.1–10: 64% (n = 2372)
10.1–20: 16% (n = 599)
>20: 6% (n = 217)
Gl2–4: 7% (n = 278);
Gl5–6: 62% (n = 2347);
Gl7: 24% (n = 916)
Gl8–10: 7% (n = 254)
T1: 42% (n = 1612)
T2: 56% (n = 2123)
T3: 2% (n = 82)
T4: 0% (n = 2)
5.8 (5.4)NR
Bhatta-Dhar 2004, retrospective comparative, USA, 1995–1999NRNo PLND196NR<65: 74% (n = 146)≤4: 15% (n = 30)
4–10: 85% (n = 166)
NRT1–T2a: 95% (n = 186)
T2b–T2c: 5% (n = 10)
T3a: 23% (n = 45)
T3b: 1%
(n = 2)
≤6: 60% (n = 117)
≥7: 40% (n = 79)
NRNANABFFS
PLND140<65: 76% (n = 107)≤4: 14% (n = 19)
4–10: 86% (n = 121)
T1–T2a: 95% (n = 133)
T2b–T2c: 5%
(n = 7)
T3a: 34%
(n = 48)
T3b: 4%
(n = 5)
≤6: 54% (n = 76)
≥7: 46% (n = 64)
NRNR
Fergany 2000, retrospective comparative, USA, 1986–1999Open: 100%No PLND20338
(R: 1–141)
≤65: 74% (n = 150)≤4: 15% (n = 31)≤6: 100% (n = 203)≤cT1–T2a: 95% (n = 193)pT3a: 23% (n = 47)
pT3b: 1% (n = 2)
≤6: 61% (n = 123)NRNRNABFFS
PLND372≤65: 72% (n = 267)≤4: 24% (n = 88)≤6: 100% (n = 372)≤cT1–T2a: 88% (n = 327)pT3a: 41% (n = 153)
pT3b: 4% (n = 14)
≤6: 60% (n = 223)2% (n = 6)
Limited/standard PLND versus (super)-extended PLND
Hatzichristodoulou 2015, retrospective comparative, 2007–2012Open: 100%ePLND26248
[R: 24–84]
64.9 (7.5)8.3 (6.3)6: 0% (n = 0)
7: 88.6% (n = 232)
8: 8.0% (n = 21)
9: 3.4% (n = 9)
≤T1c: 57.3% (n = 150) >T1c: 42.7% (n = 112)pT2: 76.3% (n = 200) pT3a: 13% (n = 34) pT3b: 9.9% (n = 26) pT4: 0.8% (n = 2)6: 40.1% (n = 105) 7: 47.7% (n = 125) 8–10: 12.2% (n = 32)NR20.4 (9.7)NRBFFS
lPLND19864.6 (7.8)9.9 (7.8)6: 100% (n = 198) 7: 0% (n = 0) 8: 0% (n = 0) 9: 0% (n = 0)≤T1c: 74.7% (n = 148) >T1c: 25.3% (n = 50)pT2: 80.8% (n = 160) pT3a: 13.6% (n = 27) pT3b: 5.6% (n = 11) pT4: 0%
(n = 0)
6: 44.9% (n = 89) 7: 50.6% (n = 100) 8–10: 4.5% (n = 9)4.7 (4)
Yuh 2015, retrospective comparative, AUA, USARobotic: 100%lPLND326NRNRNRNRNRpT3: 30% (n = 98)NR21% (n = 68)63%BFFS, OS
ePLND259pT3: 34% (n = 88)29% (n = 75)2015%
Lestingi 2015, RCT, AUA, BrazilNRlPLND108NRNRNRNRNRNRNRNR3.54.4%BFFS
ePLND10818.810.7%
Nyushko 2014, retrospective comparative, EMUC, Russian FederationNRNo PLND
PLND
22929.6 (24.9)
[3–125]
NR23.8
(23.3)
6: 24.9%
(n = 57) 3 + 4: 25.3% (n = 58)
4 + 3: 29.7% (n = 68)
8–10: 16.2% (n = 37)
T1b–2c: 48.5% (n = 111)
T3a–b: 51.5% (n = 118)
NRNRNR23 (9)
[2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], and [53]
NR3-yr BCR
Kim 2013, retrospective comparative, South KoreaRobotic: 100%sPLND2943665
[R: 60–69]
8.4
[R: 5.3–37.7]
≤6: 33.4% (n = 98)
7: 48.3% (n = 142)
≥8: 18.3% (n = 54)
T1: 66.3% (n = 195)
T2: 21.4% (n = 63)
T3: 12.3% (n = 36)
T2: 62.2% (n = 183)
T3a: 28.6% (n = 84)
T3b: 9.2% (n = 27)
NRNR12 [R: 9–16]3.4% (n = 10)BFFS
ePLND17066 [R: 62–70]10.4
[R: 6.6–16.1]
≤6: 17.7% (n = 30)
7: 39.4%
(n = 67)
≥8: 42.9% (n = 73)
T1: 45.9% (n = 78)
T2: 41.2% (n = 70)
T3: 12.9% (n = 22)
T2: 56.5% (n = 96)
T3a: 28.8% (n = 49)
T3b: 14.7% (n = 25)
21 [R: 16–25]13.5% (n = 23)
Nyushko 2013, retrospective comparative, EMUC, Russian FederationNRsPLND49.3% (n = 442)30 m
(3–170)
NR14.3 (12.6)NRNRNRNRNR13 (6)NRBCR
5-yr OS
CSS
ePLND50.7% (n = 434)16.2 (15.1)26 (9)
Lim 2013, retrospective comparative, AUA, South KoreaRobotic: 100%ePLND17036 m
(R: 12–77)
NRNRNRNRNRNRNR21 [NR]NR5-yr BFFS
sPLND29412 [NR]
Jung 2012, retrospective comparative, South Korea, 2005–2010Robotic: 100%sPLND15524
[IQR: 15–34]
66
[IQR: 61–70]
8.7
[IQR: 5.8–14.3]
<7: 32.3% (n = 50)
7: 33.5% (n = 52)
>7: 34.2% (n = 53)
≤T2: 43.9% (n = 68)
T3: 56.1% (n = 87)
T2: 51.6% (n = 80)
T3a: 38.1% (n = 59)
T3b: 9.0% (n = 14)
T4: 1.3% (n = 2)
<7: 23.9% (n = 37)
7: 50.9% (n = 79)
>7: 25.2% (n = 39)
R1: 37.4% (n = 58)15
[IQR: 11–19]
5.2%
(n = 8)
BFFS
ePLND4513
[IQR: 10–17]
67
[IQR: 63–72]
15.5
[IQR: 7.6–24.6]
<7: 11.1% (n = 5)
7: 28.9% (n = 13)
>7: 60% (n = 27)
≤T2: 28.9% (n = 13)
T3: 71.1% (n = 32)
T2: 35.6% (n = 16)
T3a: 53.3% (n = 24)
T3b: 8.9% (n = 4)
T4: 2.2%% (n = 1)
<7: 6.7% (n = 3)
7: 42.2% (n = 19)
>7: 51.1% (n = 23)
R1: 55.6% (n = 25)24
[IQR: 18–28]
22.2%
(n = 10)
Allaf 2004, retrospective comparative, USA, 1992–2003Open: 100%lPLND186593.6 (NR)57.9
(R: 35–74)
7.2 (NR)NRNR≥T3a: 32% (n = 597)≤6: 64.2% (n = 1198)
7: 30.8% (n = 575)
8–10: 4.8% (n = 90)
R1: 9.2% (n = 172)8.9 (NR)1.2% (n = 22)BFFS
ePLND213594.8 (NR)56.7
(R: 33–74)
7.1 (NR)≥T3a: 32.2% (n = 688)≤6: 67% (n = 1431)
7: 28.6% (n = 610)
8–10: 3.8% (n = 82)
R1: 8.4% (n = 179)11.6 (NR)3.3% (n = 71)

AUA = American Urological Association; BCR = biochemical recurrence; BF = biochemical failure; BFFS = BF-free survival; CSS = cancer-specific survival; EAU = European Association of Urology; EMUC = European Meeting on Urological Cancers; ePLND = extended PLND; GCS = Global Cancer Summit; IQR = interquartile range; lap = laparoscopic; LFFS = local failure-free survival; lPLND = limited PLND; MFS = metastases-free survival; MIES-RP = minimum incision endoscopic radical prostatectomy; NA = not available; NR = not reported; OS = overall survival; PCSM = prostate cancer–specific mortality; PSA = prostate-specific antigen; PLND = pelvic lymph node dissection; R = range; RCT = randomized clinical trial; sPLND = standard PLND; WCE = World Congress of Endourology.

Italic font denotes congress abstracts. Data for categorical variables are reported as frequency (proportion). Data for continuous variables are reported as either median [range or IQR] or mean (range).

Table 2

Baseline characteristics of studies addressing non-oncological outcomes

Study ID, design, country, recruitment periodSurgical routeTreatmentNFollow-up (mo)Age (yr)Initial PSA (ng/ml)Biopsy
Gleason score
Clinical
T stage
Pathologic
T stage
Pathologic
Gleason score
Surgical margin statusNumber of lymph nodes dissectedNumber of positive lymph nodesOutcomes reported on
No PLND versus any PLND
Ostby-Deglum 2015, retrospective comparative,
Denmark and Norway, 2005–2010
Robotic: 100%No PLND6093.0
[0.5–6.1]
63
[42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62], [63], [64], [65], [66], [67], [68], [69], [70], [71], [72], [73], [74], [75], [76], [77], and [78]
NRNRNRNRNRNRNRNRInsufficient erection
PLND
Violette 2015, retrospective comparative,
Canada, 2005–2012
Robotic: 100%No PLND392NR60 (7)6.9 (3)6: 58.9% (n = 231)
7: 41.1% (n = 161)
NRNRNRNRNRNROT
PLND
Tyritzis 2015, prospective comparative, multicenter, Sweden, 2008–2011Open: 24%
Robotic: 76%
No PLND2997NR63.5
[37.2–75.0]
6.6
[0.1–20.0]
≤6: 58.1% (n = 1732)
3 + 4: 33.9% (n = 1011)
4 + 3: 6.1% (n = 182)
≥8: 1.8%
(n = 54)
Missing: n = 18
T1: 65.5% (n = 1914)
T2: 33.2%
(n = 969)
T3: 1.3%
(n = 38)
Missing: n = 76
T2: 77.2% (n = 2266)
T3: 22.6% (n = 662)
T4: 0.2% (n = 6)
Missing: n = 43
≤7: 96.2% (n = 2846)
≥8: 3.8% (n = 113)
Missing n = 38
NRNRNRDVT, PE
PLND54764.8
[42.3 – 75.0]
9.4
[0.7–20.0]
≤6: 13%
(n = 71)
3 + 4: 31.3% (n = 171)
4 + 3: 28.9% (n = 158)
≥8: 26.7% (n = 146)
Missing: n = 1
T1: 35.1%
(n = 187)
T2: 52.2%
(n = 278)
T3: 12.8%
(n = 68)
Missing n = 14
T2: 48% (n = 258)
T3: 50.5% (n = 271)
T4: 1.5%
(n = 8)
Missing: n = 10
≤7: 78.8% (n = 423);
≥8: 21.2% (n = 114); Missing n = 10
Boehm 2015, retrospective comparative, 1992–2011Open: 95%
Robotic: 5%
No PLND4884NR64 [59], [60], [61], [62], [63], [64], [65], [66], and [67]NRGl6 29.2% (n = 3421)
3 + 4 53.8% (n = 6303)
4 + 3 13.0% (n = 1529)
≥l8 3.8% (n = 443)
NRpT2: 69.7% (n = 8172)
pT3a: 19.8% (n = 2327)
≥pT3b: 10.4% (n = 1223)
NRNRNRNRBlood transfusion
PLND6810
Cole 2015, retrospective comparative, AUA, SwedenOpen: 66%
Robotic: 34%
No PLND17171NRNRNRNRNRNRNRNRNRNR90-d perioperative mortality
PLND5191
Jeong 2015, prospective comparative, EAU, South KoreaRobotic: 100%No PLND18130.7 (11.7) [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], and [55]NR8.8 (9.2)
NRT2a–b: 21.0% (n = 38)
T2c: 47%
(n = 85)
T3a–4: 32%
(n = 58)
NRNRNRNRNRIncontinence
PLND
Gandaglia 2014, retrospective comparative, EAU, ItalyRobotic: 100%No PLND1402NR62.7NRNRNRNRNRNRNRNR30-d readmission
PLND
Liss 2013, retrospective comparative, Germany, 2007–2011Robotic: 100%
No PLND
207NR61 (6.9)
63 (6.8)
61 (7.2)
4.9 (4.0–6.5)
≤6: 93.5% (n = 188)
7: 4.5% (n = 9)
≥8: 2% (n = 4)
T1: 78.3% (n = 162)
T2: 21.7% (n = 45)
T3: 0% (n = 0)
T1: 92.3% (n = 191)
T2: 6.8% (n = 14)
T3: 1% (n = 2)
NRNRNANAOT, eBL, transfusion rate, LoS, complication rate, lymphocele rate
sPLND2316.1 (4.4–9.2)
≤6: 58.9% (n = 136)
7: 39.4% (n = 91)
≥8: 1.7% (n = 4)
T1: 58.9% (n = 136)
T2: 39.4% (n = 91)
T3: 1.7% (n = 4)
T1: 72.7% (n = 168)
T2: 26.4% (n = 61)
T3: 0.9% (n = 2)
18 [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], and [25]0.3% (n = 13)
ePLND548.5 (5.5–13.5)
≤6: 27.8% (n = 15)
7: 68.5% (n = 37)
≥8: 3.7% (n = 2)
T1: 27.8% (n = 15)
T2: 68.5% (n = 37)
T3: 3.7% (n = 2)
T1: 42.6% (n = 23)
T2: 55.6% (n = 30)
T3: 1.9% (n = 1)
20 [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], and [28]2% (n = 24)
van der Poel 2012, retrospective comparative, The Netherlands, 2006–2011Robotic: 100%No PLND464
NR60.7 (6.2)48.3% (27)< 7: 90.5% (n = 420)
7: 8.6% (n = 40)
>7: 0.7% (n = 4)
T1: 36.4% (n = 169)
T2: 61.4% (n = 285)
T3: 2.2% (n = 10)
T0: 1.5% (n = 7)
T2: 84.5% (n = 392)
T3: 11.0% (n = 51)
T4: 3.0% (n = 14)
<7: 65.7% (n = 305)
7: 29.1% (n = 135)
>7: 5.2% (n = 24)
NR0NALymphocele, DVT, Clavien grade, hematoma, ileus, anastomosis dehiscence
sPLND44062.5 (5.8)47.9 (23.2)<7: 25.9% (n = 114)
7: 54.1% (n = 238)
>7: 20% (n = 88)
T1: 34.1% (n = 150)
T2: 59.3% (n = 261)
T3: 20.7 (n = 91)
T0: 0.2% (n = 1)
T2: 59.8% (n = 263)
T3: 34.3% (n = 151)
T4: 5.7% (n = 25)
<7: 65.7% (n = 305)
7: 29.1% (n = 135)
>7: 5.2% (n = 24)
14 [11], [12], [13], [14], [15], [16], [17], [18], and [19]8.4% (n = 37)
Schmitges 2012, retrospective comparative, Canada/USA /Italy, 1999–2008Open: 93%
Minimally invasive: 7%
No PLND36 699NR61.7 (7.2)NRNRNRNRNRNRNRNx: 56.8% (n = 20 862)
N0-1: 43.2% (n = 15 837)
DVT
PLND
Schmitges 2012, retrospective comparative, USA, 1999–2008Open: 93%
Minimally invasive: 7%
No PLND20 862NRNRNRNRNRNRNRNRNRNRLoS, hospital charges, rectal laceration rate
PLND15 837
Gandaglia, retrospective comparative, Italy, 2008–2010Open: 100%No PLND16133.262.6 (IQR: 47.8–77.8)
5.43 (IQR 0.25–10)
5: 14.9% (n = 24) 6: 85.1% (n = 137)
T1c: 75.9% (n = 122)
T2a: 24.1% (n = 39)
T2: 96.3% (n = 155)
T3a: 3.7% (n = 6)
T3b: 0% (n = 0)
2–6: 59% (n = 95)
7: 41% (n = 66)
8–10: 0% (n = 0)
NR0NRErectile function recovery rate
ePLND23562.3 (IQR 40.5–78.9)
6 (IQR 0.57–10)
5: 23% (n = 54)
6: 77% (n = 181)
T1c: 62% (n = 147)
T2a: 38% (n = 88)
T2: 79.1% (n = 186)
T3a: 15.3% (n = 36)
T3b: 5.5% (n = 13)
2–6: 46% (n = 108)
7: 48.9% (n = 115)
8–10: 5.1% (n = 12)
20 [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], and [40]
Keskin 2012, retrospective comparative, ERUS, TurkeyRobotic: 100%ePLND235NRNRNRNRNRNRNRNR18 (7.55)NROT
eBL
No PLND279NANA
Hamdan 2012, retrospective comparative, ASCO, USARobotic: 100%ePLND419NRNR7.3≤6: 18%
≥7: 82%
NR≤T2: 61%
≥T3: 39%
NRNRNRNRVTE
No PLND3795.3≤6: 87%
≥7: 13%
≤T2: 88%
≥T3: 12%
Schmitges 2012, prospective comparative, Germany/ Canada/USA/Austria, 2006–2009Open: 100%No PLND580NR64 (R: 37–77)6.3 (R: 0.5–93)6: 44.2% (n = 637)
7: 35.6% (n = 513)
≥8: 8.8% (n = 127)
T1: 85.4% (n = 1230)
T2: 14.1% (n = 203)
T3: 0.6% (n = 8)
T2: 70.2% (n = 1011)
T3: 29.8% (n = 430)
6: 28.9% (n = 417)
7: 66.7% (n = 961)
8: 4.4% (n = 63)
NRNRNx: 40.2% (n = 579)
N0: 54.7% (n = 788)
N1–2: 5.1% (n = 74)
RBC transfusion, prolonged drainage, pelvic lymphocele
lPLND792
ePLND69
Jacobs 2012, retrospective comparative, AUA, The NetherlandsEERPE: 100%PLND14328 m64 (44–74)13.2 (0.87–190NRNRT2: 69% (n = 146)
T3: 30% (n = 63)
T4: 0.33% (n = 1)
Tx: 0.67% (n = 2)
NRPos: 36% (n = 77)NRNROT
No PLND69
Touijer 2011, retrospective comparative, USA,
2003–2007
Lap: 100%lPND174NRNR7 [5], [6], [7], [8], [9], [10], and [11]<7: 14%
7: 71%
8–10: 15%
T1: 61%
T2a: 14%
>T2b: 24%
NRNRNR9 [6], [7], [8], [9], [10], [11], [12], and [13]4.5%OT, postoperative complications
sPLND5956 [5], [6], [7], [8], and [9]<7: 11%
7: 72%
8–10: 14%
T1: 57%
T2a: 18%
>T2b: 24%
13 [9], [10], [11], [12], [13], [14], [15], [16], [17], and [18]14.3%
No PLND202NRNRNRNANA
Yong 2011, retrospective comparative, USA, 2003–2009Robotic: 100%No PLND182NRNRNRNRNRNRNRNRNRNROT
PLND341
Eifler 2011, retrospective comparative, USA, 2001–2009Lap: 100%No PLND302>357.7 (6.7)
4.8 (NR)
≥7: 15.6% (n = 47)NRNRNRNR00OT, VTE
PLND46857.8 (6.9)
6.5 (NR)
≥7: 42.3% (n = 198)5.7 (0–29)
0.9% (n = 4)
Khoder 2011, retrospective comparative, Germany, 2002–2004Retro: 89.8%
EERPE: 6.5%
Perineal: 3.8%
No PLND85NRNRNRNRNRNRNRNRNRNRLymphocele
PLND1078
Lin 2011, retrospective comparative, USA, 2001–2008Lap: 100%No PLND12033.9NRNRNRNRNRNRNRNRNRInguinal hernia incidence
PLND170
Dicks 2011, retrospective comparative, AUA, USARobotic: 100%PLND105NR62.89.3NRNRNRNR26%18.1NROT, eBL, LoS,
complications
No PLND11660.15.617%NANA
Hruza 2010, retrospective comparative, Germany/Italy, 1999–2008Lap: 100%No PLND76150 [IQR: 26–72]63.8 (6.15)7.6 [IQR: 5.3–11.5]NR<T3a: 70.2% (n = 1486)T2: 57.4% (n = 1261)
T3a: 26.5% (n = 588)
T3b: 11.8% (n = 260)
T4: 4% (n = 89)
4–5: 10.8% (n = 229)
6: 31.8% (n = 676)
7: 48.1% (n = 1020)
8–10: 9.3% (n = 197)
R0: 76.6% (n = 1683)NRNAComplication rate
PLND14381.9% (n = 41)
Zorn 2009, retrospective comparative, USA, 2003–2007Robotic: 100%No PLND859NR59.2 (R: 40–77)5.5 (R: 0.06–32)6: 81% (n = 696)
7: 19% (n = 163)
cT1c: 71% (n = 618)
cT2a–cT2b: 29% (n = 241)
NR6: 69.3% (n = 595)
7: 28.8% (n = 247)
8–10: 1.9% (n = 17)
NRNANAOT, eBL, blood transfusions, LoS, postoperative complications, symptomatic lymphocele
PLND29661.0 (R: 44–85)9.0 (R: 0.89–52)6: 17% (n = 52)
7: 62% (n = 182)
8–10: 21% (n = 62)
cT1c: 61% (n = 180)
cT2a–cT2b: 38% (n = 112)
cT3: 1% (n = 4)
6: 16.2% (n = 48)
7: 67.9% (n = 201)
8–10: 15.9% (n = 47)
12.5 (IQR: 7–16)7.8% (n = 23)
Stolzenburg 2005, retrospective comparative, Germany, 2001–2004EERPE: 100%No PLND70017.3 (R: 3–39)63.4 (R: 42–77)10.7 (R: 1.4–82)NRNRT2a: 12.7 (n = 89)
T2b: 7.7% (n = 54)
T2c: 35% (n = 245)
T3a: 32.7 (n = 229)
T3b: 11.2 (n = 79)
T4: 0.6 (n = 4)
4: 11% (n = 77)
5: 19.3% (n = 135)
6: 23% (n = 161)
7: 35.4% (n = 248)
8: 8.3% (n = 58)
9: 2.4% (n = 17)
10: 0.6% (n = 4)
R1: 19.7% (n = 138)NRNROT
PLND
Limited/standard PLND versus (super)-extended PLND
Hatzichristodoulou 2015, retrospective comparative, Germany, 2007–2012Open: 100%ePLND26248
[R: 24–84]
64.9 (7.5)8.3 (6.3)6: 0% (n = 0)
7: 88.6% (n = 232)
8: 8.0% (n = 21)
9: 3.4% (n = 9)
≤T1c: 57.3% (n = 150) >T1c: 42.7% (n = 112)pT2: 76.3% (n = 200) pT3a: 13% (n = 34) pT3b: 9.9% (n = 26) pT4: 0.8% (n = 2)6: 40.1% (n = 105) 7: 47.7% (n = 125) 8–10: 12.2% (n = 32)NR20.4 (9.7)NRContinence recovery rate (12 mo), Spontaneous EF recovery (12 mo), Trifecta rates (2-yr)
lPLND19864.6 (7.8)9.9 (7.8)6: 100% (n = 198) 7: 0% (n = 0) 8: 0% (n = 0) 9: 0% (n = 0)≤T1c: 74.7% (n = 148) >T1c: 25.3% (n = 50)pT2: 80.8% (n = 160) pT3a: 13.6% (n = 27) pT3b: 5.6% (n = 11) pT4: 0% (n = 0)6: 44.9% (n = 89) 7: 50.6% (n = 100) 8–10: 4.5% (n = 9)4.7 (4)
Hoshi 2015, retrospective comparative, Japan, 1988–2013Open: 100%sPLND59940 [R: 1–261]NRNRNRNRNRNRNRNRHigh risk: 7.1% (n = 13) Int risk: 0.6% (n = 1) Low risk: 0% (n = 0)eBL, lymphocele, intra- and postoperative complications
Semi-ePLND131High risk: 20% (n = 12) Int risk: 3.3% (n = 1) Low risk: 0% (n = 0)
Lestingi 2015, RCT, AUA, BrazilNRlPLND108NRNRNRNRNRNRNRNR3.54.4%eBL, OT, LoS, Clavien
ePLND10818.810.7%
Schwerfeld-Bohr 2014, RCT, EAU, GermanyNRiPLND126NRNRNRNRNRNRNRNRNRNROT, lymphocele
ePLND118
Kim 2013, retrospective comparative, South Korea, 2006–2011Robotic: 100%sPLND2943665 [R: 60–69]8.4 [R: 5.3–37.7]≤6: 33.4% (n = 98)
7: 48.3% (n = 142)
≥8: 18.3% (n = 54)
T1: 66.3% (n = 195)
T2: 21.4% (n = 63)
T3: 12.3% (n = 36)
T2: 62.2% (n = 183)
T3a: 28.6% (n = 84)
T3b: 9.2% (n = 27)
NRNR12 [R: 9–16]3.4% (n = 10)complication rate, lymphocele, lymphedema, neuropraxia
ePLND17066 [R: 62–70]10.4 [R: 6.6–16.1]≤6: 17.7% (n = 30)
7: 39.4% (n = 67)
≥8: 42.9% (n = 73)
T1: 45.9% (n = 78)
T2: 41.2% (n = 70)
T3: 12.9% (n = 22)
T2: 56.5% (n = 96)
T3a: 28.8% (n = 49)
T3b: 14.7% (n = 25)
21 [R: 16–25]13.5% (n = 23)
Yuh 2013, retrospective comparative, Italy, 2008–2012Robotic: 100%lPLND204NR64 [IQR: 58–70]5.9 [IQR: 4.4–9.1]
6: 6.4% (n = 13)
3 + 4: 54.9% (n = 112)
4 + 3: 22.1% (n = 45)
8: 12.2% (n = 25)
9: 4.4% (n = 9)
T1: 72.1% (n = 147)
T2:27.4% (n = 56)
T3: 0.5% (n = 1)
T2a/b: 7.4% (n = 15)
T2c: 57.8% (n = 118)
T3a: 23.5% (n = 48)
T3b: 11.3% (n = 923)
NRNR7 (IQR 5–9)3.9% (n = 8)eBL, OT, complication rate, lymphocele, DVT, major complications, discharge at d 1, lymphocele + DVT
ePLND20264 [IQR: 58–69]5.5 [IQR: 4.2–8.3]
6: 5.9% (n = 12)
3 + 4: 59.9% (n = 112)
4 + 3: 19.8% (n = 40)
8: 11.4% (n = 23)
9: 3.0% (n = 6)
T1: 68.8% (n = 139)
T2:30.2% (n = 61)
T3: 1% (n = 2)
T2a/b: 12.4% (n = 25)
T2c: 60.7% (n = 122)
T3a: 16.8% (n = 34)
T3b: 10.4% (n = 21)
21.5 (IQR 17–27)11.9% (n = 24)
Jung 2012, retrospective comparative, South Korea, 2005–2010Robotic: 100%sPLND15524
[IQR: 15–34]
66
[IQR: 61–70]
8.7
[IQR: 5.8–14.3]
<7: 32.3% (n = 50)
7: 33.5% (n = 52)
>7: 34.2% (n = 53)
≤T2: 43.9% (n = 68)
T3: 56.1% (n = 87)
T2: 51.6% (n = 80)
T3a: 38.1% (n = 59)
T3b: 9.0% (n = 14)
T4: 1.3% (n = 2)
<7: 23.9% (n = 37)
7: 50.9% (n = 79)
>7: 25.2% (n = 39)
R1: 37.4% (n = 58)15
[IQR: 11–19]
5.2%
(n = 8)
OT, PLND time, eBL, LoS, PLND-related complications
ePLND4513
[IQR: 10–17]
67
[63], [64], [65], [66], [67], [68], [69], [70], [71], and [72]
15.5
[IQR: 7.6–24.6]
<7: 11.1% (n = 5)
7: 28.9% (n = 13)
>7: 60% (n = 27)
≤T2: 28.9% (n = 13)
T3: 71.1% (n = 32)
T2: 35.6% (n = 16)
T3a: 53.3% (n = 24)
T3b: 8.9% (n = 4)
T4: 2.2%% (n = 1)
<7: 6.7% (n = 3)
7: 42.2% (n = 19)
>7: 51.1% (n = 23)
R1: 55.6% (n = 25)24
[IQR: 18–28]
22.2%
(n = 10)
Hoshi 2012, retrospective comparative, AUA, JapanNRePLND124NRNRNRNRNRNRNRNRNRNRComplications, lymphocele, eBL
sPLND700
Dundee 2011, retrospective comparative, AUA, AustraliaLap: 100%ePLND289NRNR11.9 (NR)
NRcT1: 28%
cT2: 60%
cT3: 12%
cT1: 39%
cT2: 55%
cT3: 6%
NRNRNR12.3 (4–42)NROT, eBL
Transfusions, LoS, complications
sPLND24210.3 (NR)4.6 (1–8)
Sonnleithner 2010, prospective comparative, EAU, AustriaNRePLND62NR62 [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62], [63], [64], [65], [66], [67], [68], [69], [70], [71], [72], [73], [74], [75], [76], [77], [78], and [79]8.3
(R: 1.2–55.4)
NRNRNRNRNRNRNRMajor complications
sPLND85
No PLND149
Eden 2010, retrospective comparative, UK, 2000–2008Lap: 100%sPLND311NR63 [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62], [63], [64], [65], [66], [67], [68], [69], [70], [71], [72], [73], [74], [75], and [76]11 [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], and [20]7 [4], [5], [6], [7], [8], [9], and [10]T1: 32.8% (n = 102)
T2: 63% (n = 196)
T3: 4.2% (n = 13)
NRNRNR6.1 [2], [3], [4], [5], [6], [7], and [8]NRTransfusion rate, eBL, OT, LoS, complication rate
ePLND12163 [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62], [63], [64], [65], [66], [67], [68], [69], [70], [71], [72], [73], and [74]8 [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], and [15]
7 [6], [7], [8], [9], and [10]
T1: 33.1% (n = 40)
T2: 57% (n = 174)
T3: 9.9% (n = 12)
17.5 [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], and [23]
Naselli 2010, retrospective comparative, Italy, 2004–2010NRlPLND98≥6 mo
NR6.43
[R: 1.95–65]
NRNR<T3: 74.5% (n = 73)
T3a: 22.4% (n = 22)
T3b: 8.2% (n = 8)
≤6: 46.9% (n = 46)
7: 46.9% (n = 46)
8–10: 6.1% (n = 6)
NR6
[R: 2–14]
N1:
1% (n = 2)
Lymphocele, reintervention
ePLND2497.22
[R: 2.2–98]
<T3: 67.5% (n = 168)
T3a: 30.1% (n = 75)
T3b: 15.7% (n = 39)
≤6: 36.9% (n = 92)
7: 50.6% (n = 126)
8–10: 12.5% (n = 31)
16
[R: 10–67]
N1:
11.7% (n = 29)
Lavery 2010, retrospective comparative, AUA, USARobotic: 100%ePLND77NRNRNRNRNRNRNRNR16.4NRComplications
sPLND1738.6
Lindberg 2009, retrospective comparative, Sweden, 2002–2007NRlPLND64NR64 (NR)NRNRNRNRNRNR7 [R: 3–18]N1: 6% (n = 4)
eBL, OT, lymphocele, DVT, PE, hematoma, wound infections, sepsis, complication rate
ePLND10864 (NR)17 [R: 5–40]N1: 20% (n = 22)
Musch 2008, retrospective comparative, Germany, 1993–2006Open: 100%lPLND867NR65 (6)
Unknown: 1.9% (n = 26)
4.1–10: 8% (n = 111)
10.1–20: 25.4% (n = 350)
>20: 13.1% (n = 181)
Unknown: 4.5% (n = 62)
2–6: 65.7% (n = 907)
7: 12.4% (n = 171)
8–10: 17.4% (n = 240)
Unknown: 1.2% (n = 17)
T1: 41.9% (n = 578)
T2: 50% (n = 690)
T3: 6.9% (n = 95)
Unknown: 1.7% (n = 24)
T2: 48.3% (n = 666)
T3a: 28.3% (n = 391)
T3b: 15.7% (n = 217)
T4: 5.9% (n = 82)
Unknown: 1.5% (n = 21)
2–6: 51.8% (n = 715)
7: 26.1% (n = 360)
8–10: 20.6% (n = 284)
R: 31.5% (n = 435)
NRN + : n = 148
Lymphocele, reintervention
ePLND434
Klevecka 2007, retrospective comparative, Germany, 1993–2004Open: 100%lPLND740NR65 (6)<2.6: 4.9% (n = 49)
2.6–4.0: 3.6% (n = 36)
4.1–10.0: 49.5% (n = 495) 10.1–20.0: 26.6% (n = 266)
≥20.1: 15.4% (n = 154)
2–4: 21.8% (n = 218)
5–6: 42.2% (n = 422)
7–10: 21.0% (n = 210)
Unknown: 15.0% (n = 150)
T1a/b: 3.4% (n = 34)
T1c: 32.7% (n = 327)
T2: 56.8% (n = 568)
cT3: 7.1% (n = 71)
T2a: 7.8% (n = 78)
T2b: 20.5% (n = 205)
T2c: 18.9 (n = 189)
T3a: 28.8 (n = 288)
T3b: 17.5% (n = 175)
T4: 6.5% (n = 65)
NRR1: 32.7% (n = 327)
NR10.9% (n = 109)
Lymphocele, DVT, PE, reintervention, postoperative bleeding, secondary wound healing
ePLND236
Clark 2003, RCT, USAOpen: 100%lPLND123NR61 (R: 45–75)<10: 84.6% (n = 104)≤6: 67.5% (n = 83)
7: 20.3% (n = 25)
8–10: 12.2% (n = 15)
T1c: 72% (n = 88)
T2a: 21% (n = 26)
T2b: 5.7% (n = 7)
T3: 1.3% (n = 2)
NRNRNRNR2.4% (n = 3)Lymphocele, leg edema, DVT, pelvic abscess, ureteral injury, overall unilateral complication rate
ePLND1233.3% (n = 4)
Heidenreich 2002, retrospective comparative, Germany, 1999–2000Open: 100%sPLND100NR63.5 (R: 49–72)14.9 (R: 1.6–109)5.2 (2.6)T1c: 10% (n = 10)
T2: 65% (n = 65)
T3: 25% (n = 25)
3.5 (R: 1–4)
NRNR11 (R: 6–19)
12% (n = 12)
eBL, OT, rectal lesions, lymphocele, DVT, PE, obturator nerve lesion
ePLND103NR61.8
(R: 51–71)
15.9
(R: 1.2–129)
4.6 (2.3)T1c: 8.7% (n = 9)
T2: 59% (n = 61)
T3: 32% (n = 33)
3.6 (R: 1–4)
NRNR28 (R: 21–42)
26.2% (n = 27)

ASCO = American Society of Clinical Oncology; AUA = American Urological Association; DVT = deep venous thromboembolism; eBL = estimated blood loss; EAU = European Association of Urology; EERPE = endoscopic extraperitoneal radical prostatectomy; ePLND = extended PLND; ERUS  = EAU Robotic Urology Section; IQR = interquartile range; lap = laparoscopic; LoS = length of hospital stay; lPLND = limited PLND; NA = not available; NR = not reported; OT = operating time; PE = pulmonary embolism; PLND = pelvic lymph node dissection; R = range; RBC = red blood cell; RCT = randomized clinical trial; sPLND = standard PLND; VTE = venous thromboembolism.

Italic font indicates congress abstracts. Data for categorical variables are reported as frequency (proportion). Data for continuous variables are reported as either median [range or IQR] or mean (range or IQR).

3.2.1. Characteristics of studies reporting on oncological outcomes

The baseline characteristics of studies evaluating oncological outcomes are summarized in Table 1. Overall, 29 studies were included. Specifically, 21 studies (15 full-text articles and six conference abstracts) compared no PLND versus any form of PLND, whereas eight studies (four full-text articles and four conference abstracts) compared lPLND or sPLND versus ePLND or sePLND.

3.2.2. Characteristics of studies reporting on non-oncological outcomes

The baseline characteristics of studies evaluating non-oncological outcomes are summarized in Table 2. Overall, 43 studies were included. Specifically, 25 studies (18 full-text articles and seven conference abstracts) compared no PLND versus any form of PLND, while 18 studies (12 full-text articles and six conference abstracts) compared lPLND or sPLND versus ePLND or sePLND.

3.3. Assessment of RoB and confounding

RoB and confounding was assessed for each of the individual studies, and the results are presented in Fig. 3A for studies reporting on oncological outcomes and in Fig. 3B for studies reporting on non-oncological outcomes. There was high or unclear RoB across most domains. However, some confounding factors were adequately considered through statistical adjustment in a significant proportion of studies, including stage and pathological Gleason score for studies reporting oncological outcomes (Fig. 4A), and age and BMI for studies reporting on non-oncological outcomes (Fig. 4B).

gr3a gr3b

Fig. 3

Risk of bias assessment for individual studies. (A) Oncological outcomes. (B) Non-oncological outcomes. NRS = nonrandomized study; RCT = randomized clinical trial.

gr4

Fig. 4

Risk of bias assessment across included studies. (A) Oncological outcomes. (B) Non-oncological outcomes. BMI = body mass index; pGS = pathological Gleason score.

3.4. Comparisons of intervention results

3.4.1. Oncological outcomes
3.4.1.1. No PLND versus any form of PLND

Overall, 21 retrospective comparative studies (15 full-text articles and six conference abstracts) compared no PLND versus any form of PLND for oncological outcomes (Table 3). No RCTs were identified for this comparison.

Table 3

Results from studies addressing oncologic outcomes

Study ID; design; country; recruitment periodSubgroup if applicableInterventionComparatorOutcome(s)Int (n)Comp (n)Intervention: outcomeComparator: outcomep valueComment
No PLND versus any PLND
Karl 2015, retrospective comparative, Germany, 1994–2013NAPLNDNo PLNDBFFS357179Univariate analysis: HR: 1.69 [1.25–2.29]
MVA: HR: 1.29 [0.94–1.78]
Univariate analysis: 0.001 MVA: 0.12
Gandaglia 2015, retrospective comparative, 2000–2013Patients eligible for active surveillance according to PRIASPLNDNo PLNDBCR3811329MVA: HR: 0.72 [95% CI: 0.37–1.38]0.3MVA corrected for: age, iPSA, PSM, pT, pGS, pN status
Koo 2015, retrospective comparative, South Korea, 2005–2009PSM + and undetectable PSA <6 wkPLNDNo PLNDBFFS403327Univariate analysis: 1.099 [95% CI: 0.564–2.141]0.08
Boehm 2015, retrospective comparative, 1992–2011NAPLNDNo PLNDBFFS68104884HR: 0.81 (95% CI: 0.72–0.9)<0.05pNx versus pN0 (pN + excluded)
MFSHR: 0.62 (95% CI: 0.41–0.92)<0.05
OSHR: 0.92 (95% CI: 0.74–1.14)0.46
Chen 2015, retrospective comparative, GCS, USAIntermediate-risk PCa only (but GS based on pGS, not bGS)PLNDNo PLNDCSS2657117541Unadjusted model: HR: 1.23 [0.83–1.80]
IPTW-adjusted Cox model: HR: 0.93 [0.65–1.33]
Propensity score–adjusted Cox model: HR: 1.05 [0.71–1.55]
Cox competing-risk mode: HR: 1.06 [0.71–1.57]
NS(When-adjusted: age, race, marital status, year of diagnosis, PSA, cT, pGS)
Abdollah 2014, retrospective comparative, EAU, ItalyNAPLNDNo PLND5-yr BFFS140693.3%90.6%0.4All RP
7-yr BFFS86.9%90.6%
Liss 2013, retrospective comparative, Germany, 2007–2011NAePLNDsPLNDNo PLNDBFFS5423120729.6% (n = 16)14.7% (n = 34)3.4% (n = 7)<0.001
Mitsuzuka 2013, retrospective comparative, Japan, 2000–2009Low risk diseasePLNDNo PLNDMFS14775100%100%NRMedian follow-up
PLND: 60 mo
No PLND: 26 mo
CSS100%100%NR
OS98.6% (n = 145)98.7% (n = 74)NR
BFFSNRNR0.65
Masuda 2013, retrospective comparative, Japan, 2000–2010pT2–3 N0/xPLNDNo PLNDBFFS187202MVA
Total cohort: HR: 1.26 (95% CI: 0.70–2.30)
pT2 disease: HR: 1.00 (95% CI: 0.43–2.26)
pT3 disease: HR: 1.86 (95% CI: 0.75–5.28)
pT2 R0 disease: HR: 0.50 (95% CI: 0.18–1.35)

0.45
1.0
0.19
0.17
Excluded N1
De Almeida Prado Costa 2013, retrospective comparative, WCE, FranceNAPLNDNo PLNDBFFS630166379%69%0.11
Chang 2013, retrospective comparative, AUA, CanadaNAPLNDNo PLNDCSS3353350.50 (95% CI: 0.05–5.52)0.57Follow-up 50.7 mo
Pokala 2013, retrospective comparative, AUA, USANAPLNDNo PLNDBFFS4628629130NRNS
5-yr CSS698%98%NR
10-yr CSS92%94%NR
Daimon 2012, retrospective comparative, Japan, 2002–2006NAlPLNDNo PLNDBFFS (5-yr)855490.1% (n = 77)82.4% (n = 44)0.28
BFFS (7-yr)88.3% (n = 75)82.4% (n = 44)0.28
Ost, retrospective comparative, Belgium/Italy, 1999–2008NAePLNDNo PLNDBFFS (7-yr)1794684%83%NR
HR: 0.8 [95% CI: 0.2–2.6]UnADJ: 0.96
ADJ: 0.69
LFFS (7-yr)87%88%NR
HR: 0.09 [95% CI: 0.01–0.6]UnADJ: 0.35
ADJ: 0.009
Ku 2011, retrospective comparative, South Korea, 1997–2009NAPLNDNo PLNDBF1118833.3% (n = 37)35.2% (n = 31)0.36
Logan 2011, retrospective comparative, AUA, USANAPLNDNo PLNDBCR88123NRNR0.3Median follow-up: 74 mo
Porter 2010, retrospective comparative, USA, 1954–1994NAPLNDNo PLNDPCSM342410RR: 0.7 (95% CI: 0.2–2.4)0.6
Weight 2008, retrospective comparative, USA, 1995–1999NAPLNDNo PLNDBFFS14019684% (10-yr)88% (10-yr)0.33
Berglund 2007, retrospective comparative, USA, 1995–2005NAlPLNDNo PLNDFFS (overall)396173274%70%0.11
FFS (low)82%81%0.83
FFS(intermediate)63%71%0.21
FFS (high)48%42%0.45
Bhatta-Dhar 2004, retrospective comparative, USA, 1995–1999NAPLNDNo PLNDBFFS14019686% (6-yr)88% (6-yr)0.28
Fergany 2000, retrospective comparative, USA, 1986–1999NAPLNDNo PLNDBFFS37220391% (4-yr)97% (4-yr)0.16
MVA: “not significant”0.24
Limited/standard PLND versus (super)extended PLND
Hatzichristodoulou 2015, retrospective comparative, 2007–2012NAePLNDlPLNDBFFS (7-yr)262198pT2 94.8%
pT3 81.2%
pT2 100%
pT3 94.7%
pT2: 0.011
pT3: 0.3
Yuh 2015, retrospective comparative, AUA, USANAePLNDlPLND1-yr BFFS25932692%90%0.017
2-yr BFFS85%88%
Lestingi 2015, RCT, AUA, BrazilNAePLNDlPLNDBCR1081087.6%10.1%0.68
Nyushko 2014, retrospective comparative, EMUC, Russian FederationNAePLNDPLND3-yr BFFS22927.9%15.3%0.02
Kim 2013, retrospective comparative, South KoreaNAsPLNDePLNDBFFS (3-yr)17029472.7%79.8%0.05(BFFS: propensity score–matched cohort: p = 0.497)
Nyushko 2013, retrospective comparative, EMUC, Russian FederationNAePLNDsPLNDBCR4344429.7% (42)33.4% (141)NRFollow-up 34 (28.3) mo (3–170)
5-yr OS91.1% (2.9)94.4% (4.1)>0.05
CSS99.2% (2.5)95.8% (4.1)>0.05
Deaths0.9% (4)1.7% (7)NR
Jung 2012, retrospective comparative, South Korea, 2005–2010NAsPLNDePLNDBFFS1554577.9%64.4%NS
Allaf 2004, retrospective comparative, USA, 1992–2003pN+ePLNDlPLNDBFFS (5-yr)2135186534.4%16.5%0.04
pN+ (<15% of retrieved nodes affected)42.9%10.0%0.01

AUA = American Urological Association; BCR = biochemical recurrence; BF = biochemical failure; BFFS = biochemical failure-free survival; bGS, biopsy Gleason score; CSS = cancer-specific survival; eBL = estimated blood loss; EMUC = European Meeting on Urological Cancers; ePLND = extended PLND; FFS = failure-free survival; GCS = Global Cancer Summit; GS, Gleason score; HR = hazard ratio; iPSA = initial PSA; lPLND = limited PLND; IPTW = inverse probability-of-treatment weighting; LFFS = local failure-free survival; MFS = metastases-free survival; MVA = multivariate analysis; NA = not applicable; NR = not reported; OS = overall survival; PCSM = prostate cancer-specific mortality; PE = pulmonary embolism; pGS, pathologic Gleason score; PLND = pelvic lymph node dissection; pN+, lymph node positive; PSM = positive surgical margin; RCT = randomized clinical trial; sPLND = standard PLND; WCE = World Congress of Endourology.

Italic font denotes congress abstracts.

3.4.1.1.1. Biochemical recurrence

Biochemical recurrence was evaluated in 18 studies, of which 5/18 (28%) involved lPLND, 1/18 (5%) sPLND, 3/18 (17%) ePLND, and 9/18 (50%) undefined PLND. Of these, 16 did not find any statistically significant difference between the two groups [16], [17], [18], [21], [23], [24], [25], [27], [28], [29], [30], [31], [33], [34], [35], and [36]. This negative finding also applied to the various subgroups of patients (eg, low-risk disease [23]; also pT2, pT3, or pT2 R0 disease [24]). Conversely, counterintuitive findings were observed in two different retrospective studies regarding the impact of PLND compared to no PLND on BCR [19] and [22]. Specifically, Boehm et al evaluated a cohort of 11 127 patients, including 6810 pN0 patients and 4884 pNx patients treated with radical prostatectomy between 1992 and 2011 [19]. Through multivariable Cox regression analysis, pNx was associated with a lower risk of BCR compared to pN0 (HR 0.81; 95% CI 0.72–0.9; p < 0.05). Despite the use of multivariable analysis, the significant baseline differences between the two groups may explain the higher risk of recurrence among pN0 patients. Furthermore, the extent of PLND was not reported. Conversely, Liss et al analyzed a cohort of 492 patients treated with robotic assisted radical prostatectomy between 2007 and 2011 [22]; 54 received ePLND, 231 received sPLND, and 207 did not receive any PLND. At a median follow-up of approximately 1 yr, BCR was significantly different among the three groups: 30% versus 15% versus 3.4%, respectively (p < 0.001). However, when ePLND was compared to sPLND in high-risk patients only, no significant differences were observed (p = 0.294).

3.4.1.1.2. Distant metastasis

Distant metastasis following radical prostatectomy was evaluated in two retrospective studies that reported conflicting results [19] and [23]. Mitsuzuka et al analyzed a series of 222 low-risk patients and found metastasis-free survival of 100% in both sPLND and no-PLND groups at a median follow-up of 60 and 26 mo, respectively [23]. Conversely, the already mentioned study by Boehm et al found that no PLND was associated with a lower risk of distant metastasis on multivariable analysis (HR 0.62; 95% CI 0.41–0.92; p < 0.05) [19]. As explained in the previous paragraph, baseline differences among pNx and pN0 patients as well as important selection bias may explain this finding.

3.4.1.1.3. Cancer-specific and overall mortality

Cancer-specific and overall mortality were analyzed in six studies. Of these, PLND was standard in one study [23], while its extent was not reported in the other five studies [19], [20], [26], [27], and [32]. None of these studies demonstrated any statistically significant differences in cancer-specific mortality [20], [23], [26], [27], and [32] or overall mortality [19] and [23] between PLND and no PLND. Mean follow-up was longer than 3 yr in five studies, ranging between 4 yr [19] and 11 yr [32]. One conference abstract by Pokala et al did not report information about follow-up [27].

3.4.1.2. Limited/standard PLND versus (super)-extended PLND

Overall, eight studies (four full-text articles and four conference abstracts) compared limited/standard PLND versus (super)-extended PLND for oncological outcomes (Table 3). One study was an RCT [9].

3.4.1.2.1. Biochemical recurrence

Biochemical recurrence was evaluated by all eight studies, and conflicting results were observed. In the RCT by Lestingi et al, which was reported as a conference abstract only, there was no significant difference in terms of BCR between lPLND and ePLND (p = 0.39) at median follow-up of 14.4 and 13.4 mo, respectively [9]. Similarly, ePLND did not alter BCR rates at median follow-up of 36 mo in a retrospective study by Kim et al [40]. Furthermore, ePLND did not provide better biochemical outcome in four comparative studies [39], [41], and [42]. However, all these studies were retrospective in design, and three were conference abstracts. Two additional studies showed a statistically significant benefit of ePLND over limited/standard PLND, but only in specific subgroups of patients: intermediate-risk patients (96% vs 90%; p = 0.017) [38] and pN1 patients with < 15% of retrieved nodes affected (43% vs 10%; p = 0.01) [43]. However, counterintuitive findings were observed in a retrospective study in which ePLND was associated with higher risk of 7-yr BCR compared to lPLND in pT2 patients only (5% vs 0%; p = 0.01) [37]. This result may reflect the selection bias of the study because surgeons tended to perform more extensive nodal dissection in higher-risk patients.

3.4.1.2.2. Distant metastasis

No studies reported on distant metastasis outcome.

3.4.1.2.3. Cancer-specific and overall mortality

Cancer-specific mortality was reported in one conference abstract [41] that showed that ePLND did not provide a statistically significant survival benefit over sPLND (p > 0.05). However, the median follow-up was 34 mo, which was presumably too short for addressing PCa survival outcomes.

3.4.2. Non-oncological outcomes
3.4.2.1. No PLND versus any form of PLND

Overall, 25 retrospective comparative studies (18 full-text articles and seven conference abstracts) compared no PLND versus any form of PLND for non-oncological outcomes (Table 4).

Table 4

Results from studies addressing non-oncologic outcomes

Study ID; design; country; recruitment periodSubpopulation (if applicable)InterventionComparatorOutcomes measuredN at baselineOutcome resultsReported
p values
Notes
IntComIntCom
No PLND vs any PLND
Ostby-Deglum 2015, retrospective comparative, Norway, 2005–2010NAPLNDNo PLNDInsufficient erection169440Univariate analysis: OR 0.95 [95% CI: 0.63–1.43]0.82
Violette 2015, retrospective comparative, 2005−2012NAPLNDNo PLNDOT392 aUnivariate analysis: OR 1.94 [95% CI: 1.09−3.47]
MVA: OR 1.65 [95% CI: 0.86−3.17]
Uni: 0.03
Multi: 0.13
Boehm 2015, retrospective comparative, 1992−2011NAPLNDNo PLNDBlood transfusion rate6810488411.4%9.7%0.0036
RR: 1.18 (95% CI: 1.05 – 1.32)NR
Tyritzis 2015, prospective comparative, multicenter, 2008−2011NAPLNDNo PLNDDVT54729972.9% (n = 15)0.3%% (n = 10)NR
Age-adjusted RR: 7.80 (95% CI: 3.51−17.30)
PE1.3% (n = 7)0.2% (n = 6)
Age-adjusted RR: 6.29 (95% CI: 2.11−18.73)
Cole 2015, retrospective comparative, AUA, SwedenNAPLNDNo PLND90-d perioperative mortality519117 1710.29% (n = 15)0.14% (n = 24)NR
RR: 2.07 (95% CI: 1.09−3.94)
Jeong 2015, prospective comparative, EAU, South KoreaNAPLNDNo PLNDIncontinence181NS
Gandaglia 2014, retrospective comparative, EAU, ItalyNAPLNDNo PLNDReadmission within 30 d1402MVA (HR not given)NS
Liss 2013, retrospective comparative, GermanyNAePLNDsPLNDNo PLNDOT (min)542312071861821760.211
blood loss (ml)150 [100−200]100 [100−200]100 [100−200]0.322
Blood transfusion rate1.9% (n = 1)0.9% (n = 2)2.4% (n = 5)0.436
LoS (d)1.11.31.6NR
Complication rate16.7% (n = 9)18.2% (n = 42)13.5% (n = 28)0.412
Lymphocele rate (no surgery)5.6% (n = 3)2.2% (n = 5)0% (n = 0)0.011
Lymphocele rate (surgery)0% (n = 0)3% (n = 7)0% (n = 0)0.018
van der Poel 2012, retrospective, The Netherlands, 2006−2011NAsPLNDNo PLNDLymphocele rate4404641.5% (n = 7)0% (n = 0)NR
DVT1.5% (n = 7)0% (n = 0)NR
Clavien grading1: 6.1% (n = 27)
2: 5.7% (n = 25)
3: 2.0% (n = 9)
4: 0.2% (n = 1)
1: 5.0% (n = 23)
2: 4.3% (n = 20)
3: 1.7% (n = 8)
4: 0% (n = 0)
0.147
Hematoma3.5% (n = 15)2.1% (n = 10)NR
Ileus0.3% (n = 1)0.2% (n = 1)NR
Anastomosis dehiscence1.1% (n = 4)0.2% (n = 1)NR
Schmitges 2012, retrospective comparative, Canada/USA/ Italy, 1999−2008NAPLNDNo PLNDDVT36699MVA: OR: 1.07 (95% CI: 0.67−1.69)
(corrected for: ASC, year of surgery, age, race, CCI, PLND, surgical approach)
0.78
Schmitges 2012, retrospective comparative, Canada/USA/ Italy, 1999−2008NAPLNDNo PLNDLoS >3 d1583720862OR 1.50 (95% CI: 1.26−1.78)ADJ: <0.001
Hospital charges > 37621 dollarsOR 0.84 (95% CI: 0.59−1.19)ADJ: 0.31
Rectal lacerations0.7% (n = 105)0.8% (n = 159)UnADJ: 0.27 ADJ: 0.1
Gandaglia 2012, retrospective comparative, Italy, 2008−2010NAePLNDNo PLNDErectile function recovery rate23516143.8% (n = 103) (1-yr)
49.7% (n = 117) (2-yr)
39.4% (n = 63) (1-yr)
46.6% (n = 75) (2-yr)
NR
Unadjusted HR: 0.80.3
Adjusted HR: 0.90.8
Keskin 2012, retrospective comparative, ERUS, TurkeyNAePLNDNo PLNDOT (min)235251175152<0.05
Blood loss (ml)2482820.1
Hamdan 2012, retrospective comparative, ASCO, USANAPLNDNo PLNDDVT4193491.2% (n = 5)0.28% (n = 1)0.22
Schmitges 2012, prospective comparative, Germany/ Canada/USA/ Austria, 2006−2009NAePLNDlPLNDNo PLNDTransfusion rate (ref = no PLND)69792580Limited: OR: 1.33 (95% CI: 0.79−2.34)
Extended: OR: 2.04 (95% CI: 0.76−5.51)
0.29
0.16
Prolonged drainage
(ref = no PLND)
Limited: OR: 2.81 (95% CI: 1.32−5.95)
Extended: OR: 3.38 (95% CI: 1.09−10.45)
0.007
0.035
Pelvic lymphocele (ref = no PLND)Limited: OR: 12.60 (95% CI: 5.00–31.98)
Extended: OR: 17.24 (95% CI: 5.37–55.39)
<0.001
<0.001
Jacobs 2012, retrospective comparative, AUA, The NetherlandsNAPLNDNo PLNDOT (min)14369180 (105–364)254 (120–430)NR
Touijer 2011, retrospective comparative, USA, 2003–2007NAePLNDLplndNo PLNDOT (min)595174202240 [205−270]210 [180−240]180 [170−219]<0.001
DVT1.7% (n = 10)1.1% (n = 2)1.0% (n = 2)1
PE1.3% (n = 8)0.6% (n = 1)0.5% (n = 1)0.5
Ureteral injury0.3% (n = 2)0% (n = 0)0.5% (n = 1)0.7
Clavien grading1: 8.2% (n = 49)
2: 3% (n = 18)
3: 4.5% (n = 27)
4: 0% (n = 0)
5: 0% (n = 0)
None: 84% (n = 501)
1: 4.6% (n = 8)
2: 1.7% (n = 3)
3: 4% (n = 7)
4: 0% (n = 0)
5: 0% (n = 0)
None: 90% (n = 156)
1: 0% (n = 0)
2: 1.5% (n = 3)
3: 0.5% (n = 1)
4: 0% (n = 0)
5: 0% (n = 0)
None: 90% (n = 156)
0.3
Lymphocele rate5.9% (n = 35)5.2% (n = 9)0% (n = 0)0.9
Drainage (ml)320 [195−540]235 [140−400]165 [110−250]<0.001
Yong 2011, retrospective comparative, USA, 2003−2009NAPLNDNo PLNDOT341182OR: 0.66 (95% CI: 0.37−1.18)0.159
Eifler 2011, retrospective comparative, USA, 2001−2009NAPLNDNo PLNDOT (min)4683021952070.0008
DVT1.5% (n = 7)0% (n = 0)0.047
Khoder 2011, retrospective comparative, Germany, 2002−2004NAPLNDNo PLNDLymphocele rate107885MVA: OR: 2.6 (95% CI: 1.3−4.9)0.004
Lin 2011, retrospective comparative, USA, 2001−2008NAPLNDNo PLNDInguinal hernia incidence170120HR: 1.02 (95% CI: 0.38−2.75)0.851
Dicks 2011, retrospective comparative, AUA, USANAPLNDNo PLNDOT (min)1051161911730.004
Blood loss (ml)1551490.688
LoS (d)1.41.30.647
Complication rate24.5%17.9%0.308
Hruza 2010, retrospective comparative, Germany/Italy, 1999−2008NAPLNDNo PLNDComplication rate1438761MVA: OR: 1.077 (95% CI: 0.834−1.390)0.570
Zorn 2009, retrospective comparative, USA, 2003−2007NAPLNDNo PLNDOT (min)296859224 (R: 160−320)216 (R: 120−330)0.09
Blood loss (ml)206 (R: 50−750)229 (R: 50−700)0.14
Blood transfusion rate3% (n = 9)1.7% (n = 15)0.4
LoS (d)1.32 (R: 1−5)1.24 (R: 1−4)0.4
Postoperative complications9% (n = 27)7% (n = 63)0.8
Pelvic lymphocele2% (n = 6)0% (n = 0)0.9
FFS (low)82%81%0.83
FFS (intermediate)63%71%0.21
FFS (high)48%42%0.45
Stolzenburg 2005, retrospective comparative, Germany, 2001−2004NAPLNDNo PLNDOT (min)700170115NR
Limited/standard PLND vs (super)-extended PLND
Hatzichristodoulou 2015, retrospective comparative, 2007−2012NAePLNDlPLNDContinence recovery rate
(12 mo)
26219889.7%93.4%0.204
MVA: 1.07 [0.87−1.31] (corrected for age at surgery, preoperative IIEF−5 score, iPSA, pGS, pT, prostate volume)0.508
Spontaneous EF recovery
(12 mo)
40.4%47.5%0.534
MVA: 1.11 [0.75−1.63] (corrected for age at surgery, preoperative IIEF-5, iPSA, pGS, pT, prostate volume)0.600
Trifecta rates
(2-yr)
44.1%47.5%0.451
Hoshi 2015, retrospective comparative, 1988−2013NASemi-ePLNDsPLNDBlood loss (ml)131599NRNRNS
Lymphoceles0% (n = 0)0% (n = 0)NS
Intra- and postoperative complications0% (n = 0)0% (n = 0)NS
Lestingi 2015, RCT, AUA, BrazilNAePLNDiPLNDBlood loss (ml)108108NR<0.001
OTNR<0.001
LoS (h)NR<0.001
ClavienNR0.116
Schwerfeld-Bohr 2014, RCT, EAU, GermanyNAePLNDiPLNDOT (min)118126200107NROpen 124; LRP 6, RARP 114
Lymphoceles8% (n = 10)17% (n = 20)NR
RR: 2.14 (95% CI: 1.04−4.37)0.04
Kim 2013, retrospective comparative, South KoreaNAePLNDsPLNDComplication rate17029411.8% (n = 20)2.4% (n = 7)<0.001
Lymphocele2.4% (n = 4)0.3% (n = 4)0.043
Lymphedema8.8% (n = 15)1.4% (n = 4)<0.001
Neuropraxia0.6% (n = 1)0.7% (n = 2)0.905
Yuh 2013, retrospective comparative, Italy, 2008−2012NAePLNDlPLNDBlood loss (ml)202204200 [IQR 150−250]200 [IQR 150−250]0.7
OT3 [IQR 2.9−3.3]2.8 [IQR 2.7−3.2]<0.001
Complication rate22.8% (n = 46)21.6% (n = 44)0.8
Lymphocele2.5% (n = 5)2.9% (n = 6)NR
DVT1% (n = 2)2.9% (n = 6)NR
Major complicationsMVA OR: 0.60 (95% CI: 0.25−1.46)0.3
Discharge at day 174.8% (n = 151)85.3% (n = 174)0.004
Lymphocele plus DVTNR0.3
Jung 2012, retrospective comparative, South Korea, 2005−2010NAePLNDsPLNDOT (min)45155190 [IQR: 165−211]196 [IQR: 180−224]0.027
PLND time (min)26 [IQR: 20−35]47 [IQR: 36−58]<0.001
Blood loss (ml)250 [IQR: 150−400]200 [IQR: 100−300]0.088
LoS (d)4 [IQR: 3−7]4 [IQR: 3−7]0.998
PLND-related complications3.2% (n = 5)2.2% (n = 1)1
Hoshi 2012, retrospective comparative, AUA, JapanNAePLNDsPLNDIntraoperative complications124700NS
Postoperative complicationsNS
LymphoceleNS
Blood loss (ml)NS
Dundee 2011, retrospective comparative, AUA, AustraliaNAePLNDsPLNDOT (min)289242208190<0.0001
Blood loss (ml)2432090.2
Blood transfusion rate (%)0.7% (n = 2)1.7% (n = 4)1.0
LoS (d)2.92.90.5
Complications (%)7.46.20.9
Sonnleithner 2010, prospective comparative, EAU, AustriaNAePLNDsPLNDNo PLNDMajor complications628514946%13%32%NR
Eden 2010, retrospective comparative, UK, 2000−2008NAePLNDsPLNDTransfusion rate1213112.5% (n = 3)0.8% (n = 2)0.27
Blood loss (ml)200 [10−800]200 [10−1300]0.13
OT (min)206.5 [99−331]180 [117−537]<0.001
LoS (d)3 [2−4]3 [2−5]0.77
Complication rate8.3% (n = 10)3.6% (n = 9)0.10
Naselli 2010, retrospective comparative, Italy, 2004−2010NAePLNDlPLNDSymptomatic lymphocele249989.6% (n = 24)2% (n = 2)0.028
RR: 4.723
DVT1.6% (n = 4)0% (n = 0)NR
Lavery 2010, retrospective comparative, AUA, USANAePLNDlPLNDcomplication771738%0.5%NR
Lindberg 2009, retrospective comparative, Sweden, 2002−2007NAePLNDlPLNDBlood loss (ml)10864700 [NR]1100 [NR]NR
OT difference△21 min (ePLND vs lPLND)
Lymphocele17.6% (n = 19)9.4% (n = 6)
DVT0.9% (n = 1)1.5% (n = 1)
PE4.6% (n = 5)1.5% (n = 1)
Hematoma1.9% (n = 2)0% (n = 0)
Wound infections3.7% (n = 4)0% (n = 0)
Sepsis1.9% (n = 2)0% (n = 0)
Complication rate30.6% (n = 33)12.5% (n = 8)0.007
Musch 2008, retrospective comparative, Germany, 1993−2006NAePLNDlPLNDLymphocele434867HR: 2.88 [95% CI: 1.735−4.773]<0.0001MVA corrected for age, BMI, ASA
ReinterventionHR: 2.37 [95% CI: 1.494−3.750]<0.0001
Klevecka 2007, retrospective comparative, Germany, 1993−2004NAePLNDlPLNDLymphocele2367408.1% (n = 19)2.8% (n = 21)<0.001Univariate analysis only
DVT1.3% (n = 3)1.4% (n = 10)0.93
PE0.9% (n = 2)0.8% (n = 6)0.96
Reintervention10.2% (n = 24)3.1% (n = 23)<0.0001
Postoperative bleeding3.4% (n = 8)1.6% (n = 12)0.10
Secondary wound healing2.1% (n = 5)2.2% (n = 16)0.97
Clark 2003, RCT, USANAePLNDlPLNDLymphocele1231233.3% (n = 4) (3/4 at side of extended)NRPts randomized to one side limited, one side extended
Leg edema4.1% (n = 5) (3/5 at side of extended)
DVT1.6% (n = 2) (2/2 at side of extended)
Pelvic abscess0.8% (n = 1) (1/1 at side of extended)
Ureteral injury0.8% (n = 1) (1/1 at side of extended)
Overall unilateral complication rate75% of total complications on side of extended dissection0.08
Heidenreich 2002, retrospective comparative, Germany, 1999−2000NAePLNDsPLNDBlood loss (ml)103100650 (R: 200−1950)590 (R: 150−2100)NR
OT (min)179 (R: 140−235)125 (R: 85−150)<0.03
Rectal lesions1.1% (n = 1)1% (n = 1)NR
Lymphocele10.6% (n = 9)6% (n = 6)NR
DVT4.2% (n = 4)6% (n = 6)NR
PE2.1% (n = 2)2% (n = 2)NR
Obturator nerve lesion1.1% (n = 1)2% (n = 2)NR

a Numbers for each group were not reported.

ASC = annual surgical caseload; ASCO = American Society of Clinical Oncology; AUA = American Urological Association; BMI = body mass index; CCI = Charlson comorbidity index; DVT = deep venous thromboembolism; ePLND = extended PLND; ERUS = EAU Robotic Urology Section; HR = hazard ratio; EAU = European Association of Urology; EIIF, International Index of Erectile Function; lPLND = limited PLND; LRP = laparoscopic surgery; iPSA = initial PSA; LoS = length of hospital stay; MVA = multivariate analysis; NA = not applicable; NR = not reported; OT = operating time; OR = odds ratio; PE = pulmonary embolism; pGS = pathologic Gleason score; PLND = pelvic lymph node dissection; PRIAS = Prostate Cancer Research International Active Surveillance; PSA = prostate-specific antigen; RARP = robot-assisted radical prostatectomy; RCT = randomized clinical trial; RR = relative risk; sPLND = standard PLND.

Italic font denotes congress abstracts.

3.4.2.1.1. Intraoperative and perioperative outcomes

Data were obtained from 20 retrospective studies regarding operative time, blood loss, and postoperative complications [12], [15], [19], [22], [45], [48], [49], [50], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62], and [63]. In the main, PLND was associated with a significantly higher risk of lymphocele in the majority of studies that addressed the outcome (12/16 studies). Moreover, a population-based study showed a higher 90-d mortality rate in the PLND group (0.29% vs 0.20% in the case of open surgery; 0.29% vs 0.13% in the case of robotic surgery) without statistical significance according to the conference abstract [46]. Conversely, a single-institution study did not find any significant difference on multivariable analysis for 30-d readmission rates between the two groups after adjusting for age at surgery, Charlson comorbidity index, and postoperative complications (OR not reported; p > 0.1) [47].

3.4.2.1.2. Functional outcomes

Three retrospective studies did not find any significant differences between PLND and no PLND regarding urinary continence (OR not reported) [13] and erectile function recovery (OR 0.95, 95% CI 0.63–1.43, p = 0.8; and HR 0.9; p = 0.8) [44] and [51].

3.4.2.2. Limited/standard PLND versus (super)-extended PLND

Overall, 18 studies (12 full-text articles and six conference abstracts) compared limited/standard PLND versus (super)-extended PLND for non-oncological outcomes (Table 4). Three were RCTs [9], [10], and [11].

3.4.2.2.1. Intraoperative and perioperative outcomes

In comparing lPLND versus ePLND, one RCT recruited 226 patients with intermediate-risk disease [9] and another RCT recruited 234 patients with high-risk disease [10]. In the study by Lestingi et al, ePLND was associated with statistically significant increases in operative time, intraoperative complications, bleeding, and hospital stay (p < 0.001), but not for postoperative complications according to the Clavien-Dindo scale (p = 0.12). Further details were not reported in the conference abstract [9]. Similarly, in the study by Schwerfeld-Bohr et al, ePLND prolonged surgical time by 30 min compared to lPLND. In this study, lymphocele development was the only complication that occurred significantly more often after ePLND compared to lPLND (17% vs 8%) [10]. In another RCT, 123 patients were randomized to either ePLND on the right hemi-pelvis versus lPLND on the left hemi-pelvis. Complications including lymphocele (3% vs 1%) and lower-extremity edema (3% vs 2%) occurred more commonly on the side subjected to ePLND compared to lPLND [11].

When considering data from 15 retrospective studies, conflicting results were observed. Five studies showed significantly higher intraoperative and postoperative complications in the ePLND group compared to lPLND/sPLND [14], [40], [70], [71], and [72], while five studies did not find any significant differences [42], [64], [66], [67], and [68]. Similarly, the rate of lymphocele was significantly higher in the ePLND group in four studies [40], [70], [73], and [74], while no significant differences were observed in four others [42], [64], [66], and [67].

3.4.2.2.2. Functional outcomes

One retrospective comparative study did not find any significant differences regarding urinary continence (HR 1.07, 95% CI 0.87–1.31; p = 0.5) and erectile function recovery (HR 1.11, 95% CI 0.75–1.63; p = 0.6) between ePLND and lPLND [37].

3.5. Discussion

To date, PLND represents the most accurate staging procedure to assess the presence of lymph node metastasis in PCa patients [2] and [75]. However, its therapeutic role from an oncological effectiveness perspective remains unclear. The objectives of this systematic review were to determine the benefits and harms of PLND during radical prostatectomy compared to no PLND, how the different PLND extents compare to one another, and which patients benefit most from PLND.

3.5.1. Principal findings

This systematic review, after screening almost 4000 articles, highlighted important results that deserve attention. First, the overall quality of evidence based on study design and RoB assessment of the studies included was low, and most studies were judged to have moderate to high RoB. Indeed, of 67 studies included, only three were RCTs and four were prospective NRCS, while the rest were retrospective NRCS. Furthermore, the anatomical extent of PLND was not specified in more than half of the studies included, highlighting a lack of standardized definitions for the extent of PLND in the current literature.

Second, when considering oncological outcomes, there was no good-quality evidence indicating that any form of PLND improves outcomes compared to no PLND. Of 21 studies, all of which were retrospective in nature, none showed statistically significant differences in favor of PLND when compared to no PLND for BCR, distant metastasis, or survival. Similarly, no good-quality evidence was retrieved indicating that ePLND improves oncological outcomes compared to lPLND or sPLND. Data from 13 studies, one of which was an RCT reported as a conference abstract, showed conflicting results; two studies (including the RCT) showed no differences in BCR at short-term follow-up; two studies showed no differences in BCR between the interventions for the entire cohort, but found that only particular subgroups of patients benefited from ePLND compared to lPLND/sPLND for BCR; and nine studies found no significant differences in BCR.

Finally, considering non-oncological outcomes, PLND was associated with significantly worse intraoperative and perioperative outcomes compared to no PLND in 20 retrospective studies. Functional outcomes including urinary continence and erectile function recovery were evaluated in three retrospective studies, and no significant differences were observed. Similar results were obtained when comparing lPLND or sPLND to ePLND in 18 studies.

On the basis of the current results, the therapeutic benefits of PLND during radical prostatectomy remain unproven. However, two important factors need to be considered.

  • (1) PLND may in theory be curative for particular patients with limited nodal involvement that is entirely removed at the time of surgery (direct effect). In support, a recent retrospective study showed that biochemical relapse is likely in patients with limited nodal disease after radical prostatectomy and PLND; however, clinical progression was observed in less than 50% of these patients [76]. Furthermore, an additional retrospective study showed that removal of a higher number of lymph nodes in pN1 patients was associated with improvement in cancer-specific survival [77]. However, such hypotheses need to be verified by studies providing level 1 evidence.
  • (2) PLND may represent a stratification tool for identification of patients who benefit from adjuvant treatments that improve survival outcomes (indirect effect). As an example, Abdollah et al recently identified specific categories of pN1 patients who benefited from adjuvant radiation therapy combined with adjuvant hormonal therapy [78]. Therefore, more comprehensive and accurate nodal staging through ePLND may indirectly improve the prognosis for pN1 patients.
3.5.2. Implications for clinical practice

The current EAU PCa guidelines recommend ePLND in high-risk and intermediate-risk patients for staging if the estimated risk of positive lymph nodes exceeds 5%, and recommend avoiding PLND in low-risk patients. Bearing in mind the low quality of the evidence for PLND outcomes from published data, the cautious EAU guidelines statement concerning PLND for treatment is supported by the current findings.

Indeed, PLND during radical prostatectomy should not be performed in all patients because of a lack of solid evidence regarding its oncological benefit and because of the harms associated with it. However, it is equally important not to blindly exclude PLND for all patients either, and for exactly the same reason: the lack of solid evidence disproving its oncological benefit.

Because greater PLND extent improves nodal staging [2] and [79], it is advisable to always perform ePLND whenever PLND is indicated. However, ePLND should be avoided when the harms are expected to exceed the possible benefits. Predictive models assessing the risk of lymph node metastasis represent the best available tool to facilitate decision-making.

3.5.3. Implications for further research

The current poor quality of evidence indicates a need for robust and adequately powered clinical trials with appropriate controls, standardized template definitions, standard operating procedures for pathological work-up, and adequate duration of follow-up to determine the therapeutic effectiveness of PLND in terms of oncological outcomes. Results from two ongoing prospective studies (NCT01812902 and NCT01555086) may improve the level of evidence in the future. However, the following three main factors should be considered when evaluating a RCT in this field.

3.5.3.1. Tumor

Tumor risk scoring is a fundamental step in study design, and populations with higher risks of lymph node disease should be investigated. As an example, PLND would be unlikely to have a significant effect when performed in a population of low-risk patients. Therefore, judicious patient selection is mandatory.

3.5.3.2. PLND procedure

The definition and extent of PLND represent other important factors to be considered. Indeed, even if ePLND has shown superior diagnostic accuracy compared to lPLND, it is unlikely to detect all positive lymph nodes [80]. Furthermore, several surgeon-related factors may have an important influence on the final results. As an example, in the SEAL/Association of Urogenital Oncology (AUO) AP 55/09 trial [10] rates of pN1 disease observed in the ePLND and lPLND groups were 15% and 12%, respectively. This finding suggests a surgeon-related bias towards more meticulous PLND in the lPLND group. Therefore, predefined templates should be designed and respected in future studies.

3.5.3.3. Pathological examination

Pathological evaluation of pelvic lymph nodes remains controversial, with a lack of consensus on specimen processing and node identification, as well as heterogeneity in terms of definitions, thresholds, and reporting. Indeed, there is evidence that both the surgeon and the pathologist may influence the number of lymph nodes removed and the number of positive nodes at final pathology [81] and [82]. Therefore, standard operating procedures for pathological work-up should be predefined in future studies.

In view of the fact that PLND is a morbid procedure that leads to a higher risk of complications, there is a need to consider alternative nodal staging methods such as sentinel node biopsy [83].

3.5.4. Limitations and strengths

The current study represents the first systematic review addressing the benefits and harms of different anatomical extents of PLND during radical prostatectomy. The review elements were developed in conjunction with a multidisciplinary panel of content experts (EAU Prostate Cancer Guideline Panel) that included a patient representative, and the review was performed robustly in accordance with recognized standards. Limitations include the relatively low quality of the evidence base, with the majority of studies being judged to have moderate to high RoB in most domains, especially in relation to oncological outcomes. There was also significant clinical and methodological heterogeneity across studies, with different definitions and thresholds used in describing the PLND procedure. In many instances the PLND extent was not described in detail, which made data acquisition, analysis, and interpretation difficult. Finally, the so-called Will Rogers phenomenon should also be taken into account. As an example, in studies focused on pN0 patients, those who received more extensive PLND were better staged, and were thus more likely to be actually free from lymph node involvement. Conversely, pN0 patients with fewer lymph nodes removed were less accurately staged. The less favorable survival rates observed among these individuals may be largely related to this phenomenon. Such limitations indicate that the findings of the review should be interpreted within the appropriate context.

4. Conclusions

The majority of studies showed that PLND and its extent are associated with worse intraoperative and perioperative outcomes, whereas a direct therapeutic effect is still not evident from the current literature. The current poor quality of evidence indicates a need for robust and adequately powered clinical trials. In the meantime, because of its recognized staging benefits, ePLND should be undertaken whenever PLND is indicated in appropriate patients who are judiciously selected using a risk-stratified approach.


Author contributions: Steven Joniau 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: Fossati, Joniau.

Acquisition of data: Yuan, Fossati.

Analysis and interpretation of data: Fossati, Willemse, Van den Broeck, Joniau.

Drafting of the manuscript: Fossati, Willemse, Van den Broek.

Critical revision of the manuscript for important intellectual content: Fossati, Willemse, van den Bergh, Van den Broeck, Yuan, Briers, Bellmunt, Bolla, Cornford, De Santis, MacPepple, Henry, Mason, Matveev, van der Poel, van der Kwast, Rouvière, Schoots, Wiegel, Lam, Mottet, Joniau.

Statistical analysis: None.

Obtaining funding: None.

Administrative, technical, or material support: None.

Supervision: Joniau.

Other: None.

Financial disclosures: Steven Joniau certifies 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: Erik Briers has received grant and research support from Ipsen, the European Association of Urology, and Bayer; is an ex officio board member for Europa UOMO; is an ethics committee and advisory group member for REQUITE; is a patient advisory board member for PAGMI; and is a member of SCA and EMA PCWP. Joaquim Bellmunt is a company consultant for Janssen, Astellas, Pierre Fabre, Genentech, Merck, Ipsen, Pfizer, Novartis and Sanofi Aventis. He has received research support from Takeda, Novartis, and Sanofi, and travel grants from Pfizer and Pierre Fabre. Michel Bolla has received company speaker honoraria from Ipsen and Astellas, honoraria or consultation fees from Janssen, and fellowship and travel grants from Janssen, AstraZeneca, and Astellas. Philip Cornford is a company consultant for Astellas, Ipsen, and Ferring; has received company speaker honoraria from Astellas, Janssen, Ipsen, and Pfizer; has participated in trials for Ferring; and has received fellowships and travel grants from Astellas and Janssen. Maria De Santis is a company consultant for GlaxoSmithKline, Janssen, Bayer, Novartis, Pierre Fabre, Astellas, Amgen, Eisai Inc., ESSA, Merck, and Synthon; has received company speaker honoraria from Pfizer, Takeda, Sanofi Aventis, Shionogi, Celgene, and Teva OncoGenex; has participated in trials for Pierre Fabre, Astellas, Exelixis, Bayer, and Roche; has received fellowship and travel grants from Bayer, Novartis, Ferring, Astellas, Sanofi Aventis, and Janssen; has received grant and research support from Pierre Fabre; has received honoraria from AstraZeneca; and is associated with Amgen. Malcolm D. Mason is a company consultant for Bristol-Myers Squibb, Janssen, Bayer, Sanofi, and Dendreon, and has received company speaker honoraria from Takeda and Bayer. Thomas Wiegel has received company speaker honoraria from Astellas, Takeda, Hexal, Ipsen, Janssen-Cilac, and Ferring. Thomas B. Lam is a company consultant for and has received company speaker honoraria from Pfizer, GSK, Astellas, and Ipsen. Vsevolod B. Matveev has participated in trials for Astellas, Pfizer, and Novartis, and has received company speaker honoraria from Sanofi and Astellas. Henk G. van der Poel is a company consultant for Intuitive Surgical, has participated in trials for Astellas and Steba Biotech, and has received grant and research support from Astellas. Olivier Rouvière is a company consultant for and has received company speaker honoraria from EDAP-TMS, Bracco, and Philips, and has participated in trials for EDAP-TMS and Bracco. Nicolas Mottet has received grant and research support from Takeda Pharmaceutical, Millenium, Astellas, Pierre Fabre, Sanofi, and Pasteur, and has received honoraria or consultation fees from Takeda Pharmaceutical, Millenium, Jansen, Astellas, BMS, Bayer, Ipsen, Ferring, Novartis, Nuclétron, Pierre Fabre, Sanofi, and Zeneca. Steven Joniau is a company consultant for Astellas, Ipsen, Bayer, Sanofi, and Janssen; has received company speaker honoraria from Astellas, Amgen, Bayer, Sanofi, Janssen, and Ipsen; has participated in trials for Astellas, Janssen, and Bayer; has received fellowship and travel grants from Astellas, Amgen, Bayer, Sanofi, Janssen, Ipsen, and Pfizer; and has received grant and research support from Astellas, Bayer, and Janssen. Nicola Fossati, Ann M. Henry, Thomas Van den Broeck, Roderick C.N. van den Bergh, Theo H. van der Kwast, Cathy Yuhong Yuan, Ekelechi MacPepple, Ivo G. Schoots, and Peter-Paul Willemse have nothing to disclose.

Funding/Support and role of the sponsor: None.

Acknowledgments: This systematic review was performed under the auspices of the European Association of Urology Guidelines Office Board and the European Association of Urology Prostate Cancer Guidelines Panel.

Appendix A. Supplementary data

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Footnotes

a Division of Oncology/Unit of Urology, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, Milan, Italy

b Department of Urology, Erasmus Medical Center, Rotterdam, The Netherlands

c Department of Urology, University Hospitals Leuven, and Laboratory of Molecular Endocrinology, KU Leuven, Leuven, Belgium

d Department of Urology, University Medical Centre, Utrecht, The Netherlands

e Division of Gastroenterology and Cochrane UGPD Group, Department of Medicine, Health Sciences Centre, McMaster University, Hamilton, Canada

f Patient Advocate, Hasselt, Belgium

g Bladder Cancer Center, Dana-Farber Cancer Institute, Boston, MA, USA

h Harvard Medical School, Boston, MA, USA

i Department of Radiation Therapy, CHU Grenoble, Grenoble, France

j Royal Liverpool and Broadgreen Hospitals NHS Trust, Liverpool, UK

k University of Warwick, Cancer Research Centre, Coventry, UK

l Surrey Health Economic Centre, School of Economics, University of Surrey, Guilford, UK

m Leeds Cancer Centre, St. James's University Hospital and University of Leeds, Leeds, UK

n Cardiff University, Velindre Hospital, Cardiff, UK

o N.N. Blokhin Cancer Research Center, Moscow, Russia

p Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands

q Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands

r Hospices Civils de Lyon, Radiology Department, Edouard Herriot Hospital, Lyon, France

s Department of Radiology & Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands

t Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

u Department of Radiation Oncology, University Hospital Ulm, Ulm, Germany

v Academic Urology Unit, University of Aberdeen, Aberdeen, UK

w Department of Urology, Aberdeen Royal Infirmary, Aberdeen, UK

x Department of Urology, University Hospital, St. Etienne, France

Corresponding author. Department of Urology, University Hospitals Leuven, Leuven, Belgium. Tel. +32 163 46945; Fax: +32 163 46931.

1 Both are co-first authors of this paper.

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