EURURO-5656; No. of Pages 8

Platinum Priority – Prostate CancerEditorial by XXX on pp. x–y of this issue

More Extensive Pelvic Lymph Node Dissection Improves Survival

in Patients with Node-positive Prostate Cancer

Firas Abdollah a, Giorgio Gandaglia a, Nazareno Suardi a, Umberto Capitanio a, Andrea Salonia a,Alessandro Nini a, Marco Moschini a, Maxine Sun b, Pierre I. Karakiewicz b, Sharhokh F. Shariat c,Francesco Montorsi a, Alberto Briganti a,*

a Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy; b Cancer Prognostics and Health Outcomes Unit, University of Montreal

Health Centre, Montreal, Quebec, Canada; c Department of Urology, Medical University of Vienna, Vienna, Austria

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ava i lable at www.sc iencedirect .com

journa l homepage: www.europea nurology.com

Article info

Article history:

Accepted May 15, 2014

Keywords:

Neoplasm recurrence

Prostatic neoplasms/pathology

Prostatic neoplasms/surgery

Prostatic neoplasms/mortality

Lymph node invasion

Lymph node dissection

Abstract

Background: The role of extended pelvic lymph node dissection (ePLND) in treatingprostate cancer (PCa) patients with lymph node invasion (LNI) remains controversial.Objective: The relationship between the number of removed lymph nodes (RLNs) andcancer-specific mortality (CSM) was tested in patients with LNI.Design, setting, and participants: We examined data of 315 pN1 PCa patients treatedwith radical prostatectomy (RP) and anatomically ePLND between 2000 and 2012 at onetertiary care centre. All patients received adjuvant hormonal therapy with or withoutadjuvant radiotherapy (aRT).Outcome measurements and statistical analysis: Univariable and multivariable Coxregression analyses tested the relationship between RLN number and CSM rate, afteradjusting to all available covariates. Survival estimates were based on the multivariablemodel; patients were stratified according to RLN number using points of maximumseparation.Results and limitations: The average number of RLNs was 20.8 (median: 19; interquartilerange: 14–25). Mean and median follow-up were 63.1 and 54 mo, respectively. At 10-yr,the CSM-free survival rate was 74.7%, 85.9%, 92.4%, 96.0%, and 97.9% for patients with 8, 17,26, 36, and 45 RLNs, respectively. By multivariable analyses, the number of RLNs inde-pendently predicted lower CSM rate (hazard ratio [HR]: 0.93; p = 0.02). Other predictors ofCSM were Gleason score 8–10 (HR: 3.3), number of positive nodes (HR: 1.2), and aRTtreatment (HR: 0.26; all p � 0.006). The study is limited by its retrospective nature.Conclusions: In PCa patients with LNI, the removal of a higher number of LNs during RPwas associated with improvement in cancer-specific survival rate. This implies that ePLNDshould be considered in all patients with a significant preoperative risk of harbouring LNI.Patient summary: We found that removing more lymph nodes during prostate cancersurgery can significantly improve cancer-specific survival in patients with lymph nodeinvasion.

# 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

* Corresponding author. Department of Urology, Urological Research Institute, San RaffaeleHospital, University Vita-Salute, Via Olgettina, 60, Milan 20132, Italy. Tel. +39 02 2643 7790;Fax: +39 02 2643 7298.E-mail address: briganti.alberto@hsr.it (A. Briganti).

Please cite this article in press as: Abdollah F, et al. More Extensive Pelvic Lymph Node Dissection Improves Survival in Patientswith Node-positive Prostate Cancer. Eur Urol (2014), http://dx.doi.org/10.1016/j.eururo.2014.05.011

http://dx.doi.org/10.1016/j.eururo.2014.05.0110302-2838/# 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

EURURO-5656; No. of Pages 8

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1. Introduction

Radical prostatectomy (RP) is one of the most commonly

used treatments for patients with prostate cancer (PCa)

[1,2]. However, the benefit of an extended pelvic lymph

node dissection (ePLND) is still debated. It is generally

accepted that whenever a PLND is indicated, this should be

anatomically extended [3]. Such an extensive approach

represents the only accurate staging procedure for lymph

node invasion (LNI) in PCa [4]. However, the therapeutic

impact of this ePLND (if any) is still unclear [5–13].

Results of a recent randomised clinical trial suggested

that ePLND could significantly decrease the risk of

biochemical recurrence (BCR) after RP in patients with

intermediate- or high-risk tumours [6]. However, although

BCR risk reduction is an important finding, it does not

necessarily translate into better survival. In contrast, several

observational reports failed to demonstrate any beneficial

impact of ePLND on BCR and/or survival [5,9,13]. There may

be two main reasons for this result: (1) use of limited and

nonhomogeneous PLND, which might have artificially

undermined the role of PLND, and (2) selection of patients

at lower risk of dying from PCa. These points are key, since

any therapeutic benefit associated with surgical treatments

of PCa should be tested using a proper surgical approach

(ie, ePLND) in a properly selected population (ie, patients at

higher risk of dying from the disease).

To address this issue, we tested the relationship between

the number of removed lymph nodes (RLNs) and cancer-

specific mortality (CSM) in pN1 patients treated with RP and

ePLND.

2. Materials and methods

We evaluated the data of 315 M0 pN1 PCa patients treated with RP and

ePLND between 2000 and 2012 at one tertiary care centre. Patients were

staged preoperatively with pelvic/abdominal computerised tomography

or abdominal ultrasound, bone scan, and chest x-ray. Seven surgeons

performed RP using a standardised retropubic technique. EPLNDs

consisted of excision of fibrofatty tissue along the external iliac vein,

the distal limit being the deep circumflex vein and the femoral canal.

Proximally, ePLND was performed up to and including the bifurcation of

the common iliac artery. Furthermore, all fibrofatty tissue within the

obturator fossa was removed to completely skeletonise the obturator

nerve. The lateral limit consisted of the pelvic sidewall, and the medial

dissection limit was defined by perivesical fat. In all the patients included

in our cohort, LNs along the internal iliac vessels were dissected. In some

cases, LNs located in the presacral and common iliac areas were also

removed.

Postoperatively, all patients received adjuvant hormonal therapy

(aHT), which was intended to be lifelong. However, given the retrospective

nature of the cohort, it is uncertain whether patients discontinued

treatment after a period of androgen-deprivation therapy. Additionally,

147 (46.7%) patients received aRT. ART was administered based on the

clinical judgment of each treating physician according to patient and

cancer characteristics. Radiation therapy consisted of localised radiation

delivered to the prostate and to the seminal vesicle bed with pelvic LN

irradiation (whole pelvis radiotherapy). Details of the aRT technique used

have been previously published [14]. Adjuvant treatments (both aHT and

aRT) were initiated within 90 d from RP. The institutional review board

approved the study.

Please cite this article in press as: Abdollah F, et al. More Extensivwith Node-positive Prostate Cancer. Eur Urol (2014), http://dx.do

2.1. Variable definition

All patients included in this study had complete clinical and pathology

data, which consisted of age at surgery, prostate-specific antigen (PSA)

value, D’Amico risk group (low- vs intermediate- vs high-risk) [15],

pathologic Gleason score (2–7 vs 8–10), pathologic tumour stage (pT2 vs

pT3a vs pT3b vs pT4), surgical margin status (negative vs positive),

number of removed LNs (RLNs), number of positive lymph nodes, aRT

status (no aRT vs aRT), and year of surgery.

2.2. Statistical analyses

Descriptive statistics of categorical variables focused on frequencies and

proportions. Means, medians, and interquartile ranges (IQR) were

reported for continuously coded variables. Chi-square and Mann-

Whitney tests were used to compare the statistical significance of

differences in proportions and medians, respectively.

Univariable and multivariable Cox regression analyses were used to

test the relationship between the number of RLNs and CSM rate, after

adjusting for all available covariates. Estimated survival curves were

plotted based on the multivariable model results. Survival curves were

stratified according to the number of RLNs, using the points of maximum

separation, as described by Harrell [16]. The number of RLNs was then

dichotomised according to the most informative cut-off predicting CSM.

This was obtained applying the chi-square test for every possible cut-off

value and choosing the lowest p value. Survival curves were then

stratified according to the most informative cut-off for the number of

RLNs. Finally, predicted 10-yr survival according to the number of RLNs

was plotted for the entire cohort, and after stratification according to

Gleason score and aRT status.

All statistical analyses were performed using the R statistical package

system (R Foundation for Statistical Computing, Vienna, Austria), with a

two-sided significance level set at p < 0.05.

3. Results

3.1. Baseline patient characteristics

Clinical and pathologic demographics of the cohort,

stratified by adjuvant treatment status are reported in

Table 1. The average PSA value was 24.2 ng/ml (median:

11.2 ng/ml; IQR: 6.9–24.4 ng/ml). Most of the patients

included in the study were affected by high-risk disease at

diagnosis (60%). Most patients harboured a pT3b disease

(66%), and had a pathologic Gleason score 8–10 (57%).

Average number of RLNs and positive LNs was 20.8

(median: 19; IQR: 14–25) and 3.3 (median: 2.0; IQR: 1–3),

respectively. For all examined variables, there were no

statistically significant differences between patients treated

with aRT versus without aRT (all p � 0.07).

3.2. Cox regression analyses and survival estimates

At univariable analyses, Gleason score 8–10 (hazard ratio

[HR]: 2.9), pT4 (HR: 6.7), aRT treatment (HR: 0.40), and the

number of positive LNs (HR: 1.1) were the only predictors of

CSM rate (all p � 0.02) (Table 2). At multivariable analyses,

Gleason score 8–10 (HR: 3.3) and a higher number of

positive LNs (HR: 1.2) were independently associated

with higher CSM rate (all p � 0.006) (Table 2). Conversely,

aRT treatment (HR: 0.26) and a higher number of RLNs

e Pelvic Lymph Node Dissection Improves Survival in Patientsi.org/10.1016/j.eururo.2014.05.011

Table 1 – Descriptive statistics for the cohort of 315 patients with nonmetastatic lymph node–positive prostate cancer, treated with radicalprostatectomy and pelvic lymph node dissection between 2000 and 2012 at one tertiary care centre*

Entire cohort(n = 315; 100%)

No adjuvant radiotherapy(n = 168; 53.3%)

Adjuvant radiotherapy(n = 147; 46.7%)

p value

Age, yr

Mean 65.3 65.9 64.6 0.1

Median 66 66 65

IQR 60–71 60–71 60–70

PSA, ng/ml

Mean 24.2 28.1 21.2 0.1

Median 11.2 11.4 11

IQR 6.9–24.0 7.4–26.5 6.7–22.5

Risk group

Low risk 29 (9.2) 17 (10.1) 12 (8.2) 0.8

Intermediate risk 97 (30.8) 52 (31.0) 45 (30.6)

High risk 189 (60.0) 99 (58.9) 90 (61.2)

Removed lymph nodes

Mean 20.8 21.4 20.2 0.3

Median 19 20 19

IQR 14–25 14-26 13-26

Positive lymph nodes

Mean 3.3 3.5 3.2 0.6

Median 2 1.5 2

IQR 1–3 1–3 1–3

Gleason score

2–7 136 (43.2) 81 (48.2) 55 (37.4) 0.07

8–10 179 (56.8) 87 (51.8) 92 (62.6)

Pathologic stage

pT2 21 (6.7) 13 (7.7) 8 (5.4) 0.7

pT3a 66 (21) 32 (19) 34 (23.1)

pT3b 207 (65.7) 112 (66.7) 95 (64.6)

pT4 21 (6.7) 11 (6.5) 10 (6.8)

Surgical margins

Negative 134 (42.5) 71 (42.3) 63 (42.9) 0.9

Positive 181 (57.5) 97 (57.7) 84 (57.1)

Year of surgery

Mean 2006.3 2005.9 2006.6 0.1

Median 2007 2007 2007

IQR 2006–2010 2005–2010 2006–2009

IQR = interquartile range.* Data were stratified according to adjuvant treatment status: no adjuvant radiotherapy versus adjuvant radiotherapy.

Table 2 – Univariable and multivariable Cox regression analyses predicting cancer-specific mortality in 315 pN1 prostate cancer patientstreated with radical prostatectomy, extended pelvic lymph node dissection, and adjuvant treatments

Univariable analysis Multivariable analysis

HR (95% CI) p value HR (95% CI) p value

Age, yr 1.00 (0.95–1.05) 0.8 1.00 (0.95–1.05) 0.9

PSA, ng/ml 1.00 (1–1.01) 0.1 1.00 (0.99–1.01) 0.4

Gleason score

2–7 1.00 (Ref.) – 1.00 (Ref.) –

8–10 2.99 (1.37–6.49) 0.006 3.31 (1.41–7.75) 0.006

Pathologic stage

pT2 1.00 (Ref.) – 1.00 (Ref.) –

pT3a 0.66 (0.12–3.63) 0.6 0.55 (0.09–3.2) 0.5

pT3b 0.91 (0.21–3.96) 0.9 0.57 (0.12–2.72) 0.4

pT4 6.74 (1.44–31.51) 0.01 3.53 (0.6–20.93) 0.1

Surgical margins

Negative 1.00 (Ref.) – 1.00 (Ref.) –

Positive 1.76 (0.85–3.63) 0.1 0.92 (0.4–2.13) 0.8

Adjuvant radiotherapy

No 1.00 (Ref.) – 1.00 (Ref.) –

Yes 0.4 (0.19–0.86) 0.02 0.26 (0.11–0.63) 0.003

Removed lymph nodes 1.03 (1–1.07) 0.05 0.93 (0.88–0.99) 0.02

Positive lymph nodes 1.12 (1.07–1.17) <0.001 1.16 (1.09–1.24) <0.001

Year of surgery 0.96 (0.88–1.05) 0.4 0.93 (0.84–1.02) 0.1

CI = confidence interval; HR = hazard ratio; Ref. = reference.

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EURURO-5656; No. of Pages 8

Please cite this article in press as: Abdollah F, et al. More Extensive Pelvic Lymph Node Dissection Improves Survival in Patientswith Node-positive Prostate Cancer. Eur Urol (2014), http://dx.doi.org/10.1016/j.eururo.2014.05.011

Fig. 1 – Kaplan-Meier survival estimates based on multivariable analysis, depicting cancer-specific survival rate in 315 pN1 prostate cancer patientstreated with surgery and adjuvant treatment. Patients were stratified according to (a) the total number of lymph nodes removed and (b) the mostinformative cut-off for the association between the number of nodes removed and cancer-specific survival.

E U R O P E A N U R O L O G Y X X X ( 2 0 1 4 ) X X X – X X X4

EURURO-5656; No. of Pages 8

(HR: 0.93) were independent predictors of a lower CSM rate

(all p � 0.02) (Table 2).

Survival estimates were calculated based on the multi-

variable model. Mean and median follow-up periods were

63.1 and 54 mo, respectively. Patients were stratified

according to the number of RLNs, using the points of

maximum separation (Fig. 1a). At 10 yr, the CSM-free survival

rate was 74.7%, 85.9%, 92.4%, 96.0%, and 97.9% for patients

with 8, 17, 26, 36, and 45 nodes removed, respectively

( p = 0.02). The most informative cut-off for the number of

RLNs was 14. At 10 yr, the CSM-free survival rates were

significantly higher for patients with � 14 RLNs compared to

their counterparts with <14 RLNs ( p = 0.04) (Fig. 1b).

Please cite this article in press as: Abdollah F, et al. More Extensivwith Node-positive Prostate Cancer. Eur Urol (2014), http://dx.do

Figure 2a presents the predicted 10-yr CSM-free rate for

the entire cohort by the number of RLNs. The predicted

CSM-free rate increased consistently with rising number of

RLNs, from 79.1% for patients with 10 RLNs to 97.0% for

patients with 40 RLNs. Similar trends were observed when

patients were stratified according to Gleason score and aRT

status (Fig. 2b and 2c).

4. Discussion

There is a continuing debate and uncertainty regarding the

role of ePLND in PCa patients treated with RP [5–9]. This

might be attributed to a drop in the utilisation rate of

e Pelvic Lymph Node Dissection Improves Survival in Patientsi.org/10.1016/j.eururo.2014.05.011

Gleason score 8–10

Gleason score 2–7(a) (b)

(c)

Treated without aRT

Treated with aRT

0.95

0.90

0.85

0.80

10 20 30 40 10 20 30 40

0.95

0.90

0.85

0.80

10 20 30 40

0.9

0.8

0.7

0.6

0.5

Lymph nodes removed, no. Lymph nodes removed, no.

Lymph nodes removed, no.

10-y

r can

cer-

spec

ific

surv

ival

rate

10-y

r can

cer-

spec

ific

surv

ival

rate

10-y

r can

cer-

spec

ific

surv

ival

rate

Fig. 2 – The multivariable analysis 10-yr cancer-specific survival rate predicted (a) by the total number of lymph nodes removed for the entire cohort,(b) after stratification according to Gleason score, and (c) by adjuvant radiotherapy (aRT) status.

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EURURO-5656; No. of Pages 8

ePLND, even in patients with intermediate- or high-risk

tumours. This trend was further accentuated by the

introduction of minimally invasive approaches, where the

performance of an ePLND might be more challenging and

time consuming [17]. However, omitting ePLND might

translate into less favourable cancer control outcomes and

have a detrimental impact on patient outcomes [6]. To verify

this hypothesis, we tested the relationship between the

number of RLNs and CSM risk after RP in patients with LNI.

We made several findings. First, at univariable analysis, a

direct positive relationship was evident between the

number of RLNs and the CSM rate. Specifically, a higher

number of RLNs was associated with a higher CSM rate

(HR: 1.03), with a borderline statistical significance level

( p = 0.05). However, after adjusting for all available

confounders, the relationship between the number of RLNs

and CSM rate flipped. Specifically, the removal of more LNs

was associated with lower CSM rate (HR: 0.93; p = 0.02).

The controversy between the results of univariable and

multivariable analyses might be explained as follows:

Frequently, patients with more aggressive tumours are

offered a more extended PLND. This might result in a

Please cite this article in press as: Abdollah F, et al. More Extensivwith Node-positive Prostate Cancer. Eur Urol (2014), http://dx.do

selection bias, where patients with the higher number of

RLNs are those that harbour the more aggressive tumours.

Consequently, it might seem that removing more LNs is

associated with less favourable survival (as in the case of

our univariable analysis), simply because of the selection

bias at baseline. However, multivariable analysis was able to

correct the baseline selection bias, and demonstrated that

removing more LNs is associated with a more favourable CSM

rate. Nevertheless, such a confounding association might not

be properly assessed in other cohorts where patients have

not routinely received an ePLND.

Second, our survival estimates, based on multivariable

analysis, showed that the beneficial impact of ePLND on

CSM might not appear before 20–30 mo of follow-up (Fig. 1a

and 1b). This implies that a long follow-up is necessary to

test the impact of ePLND on survival. This is another factor

that might have limited the reliability of previous reports.

Third, factors other than the number of RLNs appear to have

an impact on CSM rate in patients with LNI. Specifically,

patients with a higher grade and higher number of positive

LNs, and those not receiving aRT, appear to have less

favourable CSM rate.

e Pelvic Lymph Node Dissection Improves Survival in Patientsi.org/10.1016/j.eururo.2014.05.011

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In a previous report, Joslyn et al. [7] analysed data of

13 020 PCa patients treated initially with RP between 1988

and 1991, within the Surveillance, Epidemiology, and End

Results database. Authors found that removing four or more

LNs was associated with a more favourable survival rate in

both node-negative and node-positive patients. However,

these observations originated from historic patients that

were treated in the early PSA era. In another report,

Masterson et al. [8] examined the data of 4611 PCa patients

treated with RP, and found that the number of RLNs was not

associated with the risk of disease recurrence. However,

when selecting only pN0 patients, a higher number of RLNs

removed was significantly related to a lower BCR risk.

Additionally, Bivalacqua et al. [11] have shown patients

undergoing an ePLND had better oncologic outcomes at

10-yr follow-up compared to their counterparts receiving a

limited PLND. Conversely, other authors found the number

of RLNs was not associated with BCR and/or survival, even in

high-risk patients [5,9,12,13] It is noteworthy that most of

the reports focused exclusively on pN0 patients. This might

have resulted in a selection bias (Will Rogers phenomenon),

where pN0 patients with higher number of RLNs are better

staged and, thus, are more likely to be really free from LNI.

Conversely, pN0 patients with lower number of RLNs are

less probable to be accurately staged, and might actually

harbour an overlooked LNI. The less favourable survival

rates observed in these individuals might largely be

attributable to this. Although such an effect may have also

have partly influenced our results, we tried to minimise it

by focusing only on pN1 patients homogenously treated

with an ePLND. Specifically, one of the strengths of our

study is that it was based on men with LNI receiving

adequate extent of PLND. Given the heterogeneous natural

history of PCa, it is likely that a well-performed ePLND, as

well as any surgical treatment for PCa [18,19], exerts its

maximal effect on those who are at higher risk of dying from

PCa. Selecting individuals who are exposed to higher

cancer-specific risk and lower risk of competing causes of

death may thus maximise the effect of this extensive

surgical approach.

Our study has several clinical implications. Our findings

showed that a more extensive PLND offers better cancer

control outcomes in patients with LNI. It is noteworthy that

the risk for LNI in contemporary PCa patients is still significant

[20,21], and that accurate preoperative staging with imaging

of these individuals is not possible [4]. Consequently, an

ePLND in these men is mandatory to achieve reliable staging

and to improve survival of those with LNI.

Moreover, our results emphasise that it is necessary to be

cautious in interpreting data that originate from cohorts

where patients are not homogenously treated with an

ePLND and/or without long follow-up. Such data might

artificially undermine the benefits of ePLND. However, our

results cannot answer the clinically relevant question

regarding the optimal anatomic extent of ePLND in patients

with LNI. Certainly, all these patients should receive an

anatomic dissection of all lymphatic tissue in the obturator

fossa, as well as along the external and internal iliac vessels.

This should be invariably performed in all patients

Please cite this article in press as: Abdollah F, et al. More Extensivwith Node-positive Prostate Cancer. Eur Urol (2014), http://dx.do

whenever a PLND is indicated [3]. In addition, our results

seem to support not only a meticulous and careful

dissection of all these areas, but also of the presacral and

common iliac areas in patients with adverse PCa character-

istics, as previously recommended [22,23]. However, such

an approach can be only suggested, but not fully supported,

by our results. Indeed, while our study shows an association

between the number of LNs removed and patient survival,

the lack of data regarding the exact anatomic scheme of LND

in each patient prevents us from giving a clear recommen-

dation about this subject.

Finally, our results showed that patients with LNI might

benefit from maximising local disease control with aRT. This

corroborates our previous findings [24–26] and implies that

not all patients with LNI necessarily harbour a metastatic

disease. Indeed, patients with few positive LNs showed

excellent cancer-specific survival rates after adjusting for

postoperative treatments [12,27]. In this study, we report

the first single-institution series supporting the role of more

extensive PLND, regardless of the extent of nodal invasion.

Our study is not devoid of limitations. First, our results

were derived from retrospective, observational data.

Therefore, our findings should be considered in the context

of retrospective, observational evidence and warrant

prospective, randomised validation. Despite that an an-

atomically ePLND was routinely offered to all RP patients in

our institution, a fluctuation in the number of RLNs was

observed. Indeed, the RLNs ranged between 4 and 83. This

might be derived from individual variability related to

patient characteristics, which is inevitable, especially in

such a large cohort. Moreover, many unobserved confoun-

ders, such as surgical [28], pathologic expertise, and/or

imperceptible changes over time might have affected the LN

count [29]. Likewise, at surgeon discretion, a more extended

PLND that involved presacral and/or common iliac LNs was

performed in some patients. These unobserved confounders

might explain, at least partially, the variability in the LN

count over the study period. In this context, we would like

to highlight that the range of RLNs observed in our series is

in line with what has been reported by other esteemed

authors in large cohorts of patients treated with RP and

anatomically defined ePLND [11,29–32]. However, such

variability allowed us to test the effect between the number

of RLNs and patient survival, since it is likely that some

patients received even more meticulous PLND and a more

careful dissection of pelvic lymphatic tissue, based on the

judgment and expertise of different treating physicians.

Second, a pathology review was not performed. Despite the

variability in surgical technique and pathology reports,

which might have introduced potential biases, our data

benefited from a high expertise and standardised protocols,

given the tertiary care centre nature of our institute. Overall,

seven experienced surgeons (>150 cases each at the time of

study initiation) performed RP and ePLND. Moreover, four

pathologists examined the pathology specimens over the

study period. Although all of them applied a standardised

protocol for nodal evaluation [33], we cannot exclude that a

possible heterogeneity in nodal count may have introduced,

given the retrospective nature of our study. Third, data

e Pelvic Lymph Node Dissection Improves Survival in Patientsi.org/10.1016/j.eururo.2014.05.011

E U R O P E A N U R O L O G Y X X X ( 2 0 1 4 ) X X X – X X X 7

EURURO-5656; No. of Pages 8

regarding complication rate were not available. Fourth, all

patients included in the analyses received aHT. Conse-

quently, our observations might not be applicable in

patients with positive LNs and who received no aHT.

Moreover, the use of aRT was administered based on the

clinical judgment of each treating physician according to

patient and cancer characteristics. Although this might

have introduced a potential bias, it should be highlighted

that multivariable analysis and stratified analysis corrobo-

rate the beneficial impact of an ePLND, regardless of the

adjuvant treatment status.

5. Conclusions

Our results showed that in PCa patients with LNI, the

removal of a higher number of LNs during RP was associated

with an improvement in cancer-specific survival rate.

Particularly, the most informative cut-off for the number

of RLNs was 14. This implies that an ePLND should be

considered in all patients with a significant preoperative

risk of harbouring an LNI.

Author contributions: Alberto Briganti 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: Abdollah, Suardi, Briganti.

Acquisition of data: Gandaglia, Nini, Moschini.

Analysis and interpretation of data: Abdollah, Sun, Gandaglia, Capitano.

Drafting of the manuscript: Abdollah, Briganti.

Critical revision of the manuscript for important intellectual content:

Briganti, Salonia, Karakiewicz, Shariat, Montorsi.

Statistical analysis: Abdollah, Sun, Capitano, Gandaglia.

Obtaining funding: None.

Administrative, technical, or material support: None.

Supervision: Briganti, Saloni, Karakiewicz, Shariat, Montorsi.

Other (specify): None.

Financial disclosures: Alberto Briganti 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, consultan-

cies, 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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