KQ 9. 근치적 전립선절제술 시행시 골반림프절 절제술을 같이 시행하는 경우가 골반 림프절 절제술을 같이 시행하지 않는 경우에 비해 생존율을 높일 수 있는가? 문서 원본 보기

==개요==

전립선암 수술에 있어 골반림프절절제술(pelvic lymph node dissection, PLND)을 시행하는 환자의 선택은 림프절전이의 가능성을 고려하여 결정되고 있다. 골반림프절전이의 가능성은 술 전 전립선특이항원(PSA) 수치, 임상병기 및 조직검사 글리슨 점수를 사용하는 노모그람을 바탕으로 예측한다<sup>[1]</sup>.

그러나 중간위험 전립선암 환자에서 골반 림프절 절제술의 효용성에 있어서는 아직도 논란이 있다<sup>[2,3]</sup>. 골반 림프절 절제술은 정확한 병기의 설정 뿐만 아니라 미세 전이가 있는 일부 환자들에게 완치 기회를 제공할 수 있다는 점에서 효용이 있지만 이 자체가 수술에 따른 morbidity를 높이고 생존율에는 영향을 미치지 않는다는 연구 결과들도 보고되고 있다<sup>[2,3]</sup>.

중간위험 전립선암 환자에서 골반 림프절 절제술을 시행할 때 확대 골반 림프절 절제술을 시행함으로써 제한적 골반 림프절 절제술보다 2배 정도 전이성 병변을 더 많이 찾아 낼 수 있다<sup>[4]</sup>. 확대 골반림프절절제술의 범위는 전측면으로는 외장골정맥, 외측면으로는 외측골반벽, 내측면으로는 방광벽, 후측면으로는 골반바닥(floor of pelvis), 근위면으로는 내장골동맥, 원위면으로는 Cooper 인대를 경계로 하고 있다. Choi 등<sup>[5]</sup>은 제한적 림프절 절제술을 해도 중간위험군 및 고위험군에서 정확한 병기 설정에 도움을 줄 수 있다고 주장하였으며 개복수술과 로봇수술을 비교한 결과 고위험군에서는 개복수술이 림프절절제술 시행에 더 효과적이었다고 보고하였다.

==기존 가이드라인 요약 및 수용성, 적용성 평가==

미국의 National Comprehensive Cancer Network (NCCN) 진료지침의 저자들은 골반림프절전이의 가능성이 2%보다 높은 경우 골반림프절절제술을 시행할 것을 권고하고 있으며 이러한 기준을 적용하면 47.7%의 불필요한 골반림프절절제술을 줄일 수 있는 반면 양성림프절을 놓치게 될 가능성은 12.1% 정도로 낮음을 근거로 하고 있다<sup>[6]</sup>. NCCN 패널들은 Memorial Sloan Kettering Cancer Center (MSKCC)에서 제시하는 기준을 권장하고 있다<sup>[6]</sup>. 이 경우 골반림프절절제술은 광범위 골반림프절절제술(extended PLND) 방식으로 시행하는 것이 추천된다<sup>[7,8]</sup>. 이는 절제 림프절의 수가 증가 할수록 림프절전이를 진단하게 될 가능성이 높아져 보다 정확한 병기를 설정할 수 있다는데 근거한다<sup>[9-11]</sup>. NCCN에서는 골반림프절절제술을 시행하는 것이 생존율에 이득을 준다는 보고들을 제시하고 있으며 이는 미세전이 림프절을 제거할 수 있기 때문인 것으로 해석하고 있다<sup>[10,12-14]</sup>. NCCN에서는 골반림프절절제술은 관혈적접근법, 복강경이나 로봇보조 접근법을 통한 근치전립선절제술 시행 시 모두에서 비교적 안전하게 시행할 수 있고 세 접근법 모두 골반림프절절제술로 인한 합병증의 발생률은 유사하다고 제시하였다.

EAU 가이드라인 역시 광범위 골반림프절절제술을 통해 예후에 대한 중요한 정보를 제공 받을 수 있음을 강조하며 중간위험도 전립선암 환자에 있어 골반림프절전이의 가능성이 5%보다 높은 경우 골반림프절절제술을 시행하는 것을 권고하고 있다. 이때 Briganti nomogram<sup>[15,16]</sup> 혹은 MSKCC 노모그람을 이용하여 림프절 전이 가능성을 예측할 것을 권장한다<sup>[17]</sup>.

또한 AUA 가이드라인(2017)에서는 unfavorable 중간 위험도 전립선암(Gleason grade group 3) 환자에서 골반 림프절 절제술을 시행할 것을 권고하고 있다.

기존의 국내 전립선암 진료지침과 EAU 및 NCCN guideline에서는 골반림프절전이의 가능성이 2% (혹은 5%) 보다 높은 경우 골반림프절절제술을 시행하는 것을 권고하고 있다. 상기 연구결과들을 토대로 “기대여명이 10년 이상인 중간위험 전립선암 환자에서 근치적 전립선절제술 시행 시 림프절 전이의 가능성이 있는 경우 골반림프절 절제술을 권고한다.”라고 추천한다.

{| class="wikitable"
! colspan="5" |KQ 9. 기대여명이 10년 이상인 중간위험 전립선암 환자에서 근치적 전립선절제술 시행시 골반 림프절 절제술을 같이 시행하는 경우가 골반 림프절 절제술을 같이 시행하지 않는 경우에 비해 생존율을 높일 수 있는가?
|-
!지침(제목)
!권고
!권고등급
!근거수준
!page 
|-
|1. 2015 KUOS 
|근치적전립선절제술 시행 시에 림프절전이의 가능성이 2% 이상인 경우 골반림프절절제술을 포함하여 시행한다.
|없음
|없음
|23
|-
|2. EAU 2016
|An eLND should be performed in intermediate-risk 
Prostate cancer if the estimated risk for pN+ exceeds 5%
|B
|2b
|34, 36
|-
|3. NCCN 2016
|RP + PLND if predicted probability of lymph node metastasis ≥2%
|없음
|없음
|MS-12, PROS-4
|-
|} 
{| class="wikitable"
! colspan="2" |지침(제목)
!1. 2015 KUOS
!2. EAU 2016
!3. NCCN 2016
|-
| rowspan="4" |수용성
|인구 집단(유병률, 발생률 등)이 유사하다.
|예
|아니오
|아니오
|-
|가치와 선호도가 유사하다.
|예
|예
|예
|-
|권고로 인한 이득은 유사하다.
|예
|예
|예
|-
|해당 권고는 수용할 만하다. 
|예
|예
|예
|-
| rowspan="4" |적용성
|해당 중재/장비는 이용 가능하다. 
|예
|예
|예
|-
|필수적인 전문기술이 이용 가능하다.
|예
|예
|예
|-
|법률적/제도적 장벽이 없다. 
|예
|예
|예
|-
|해당 권고는 적용할 만하다. 
|예
|예
|예
|}

가이드라인 모두 수용 가능한 것으로 판단되고 적용성에 있어서 기존 치료 방법의 적용집단에 관한 문제로 특별한 문제는 없는 것으로 보인다.

==업데이트 근거 요약==

중간위험 그룹 중에서 소위 “low intermediate-risk” (글리슨 점수≤6, 임상병기≤2b, 전립선특이항원 10-20 ng/mL) 환자들의 경우 실제 림프절 전이가 3% 정도로 매우 낮게 보고된다. 이러한 환자군은 노모그람을 그대로 적용하여 골반임파선절제술을 시행하는 것에 신중을 기하는 것이 좋다<sup>[18,19]</sup>.

==참고문헌==

1. Clark T, Parekh DJ, Cookson MS, Chang SS, Smith ER Jr, Wells N, et al. Randomized prospective evaluation of extended versus limited lymph node dissection in patients with clinically localized prostate cancer. J Urol 2003;169:145-7.

2. Briganti A, Giannarini G, Karnes RJ, Gandaglia G, Ficarra V, Montorsi F. What evidence do we need to support the use of extended pelvic lymph node dissection in prostate cancer? Eur Urol 2015;67:597-8.

3. Briganti A, Abdollah F, Nini A, Suardi N, Gallina A, Capitanio U, et al. Performance characteristics of computed tomography in detecting lymph node metastases in contemporary patients with prostate cancer treated with extended pelvic lymph node dissection. Eur Urol 2012;61:1132-8.

4. Kim KH, Lim SK, Kim HY, Shin TY, Lee JY, Choi YD, et al. Extended vs standard lymph node dissection in robot-assisted radical prostatectomy for intermediate- or high-risk prostate cancer: a propensity-score-matching analysis. BJU Int 2013;112:216-23.

5. Choi D, Kim D, Kyung YS, Lim JH, Song SH, You D, et al. Clinical experience with limited lymph node dissection for prostate cancer in Korea: single center comparison of 247 open and 354 robot-assisted laparoscopic radical prostatectomy series. Korean J Urol 2012;53:755-60.

6. Cagiannos I, Karakiewicz P, Eastham JA, Ohori M, Rabbani F, Gerigk C, et al. A preoperative nomogram identifying decreased risk of positive pelvic lymph nodes in patients with prostate cancer. J Urol 2003;170:1798-803.

7. Briganti A, Blute ML, Eastham JH, Graefen M, Heidenreich A, Karnes JR, et al. Pelvic lymph node dissection in prostate cancer. Eur Urol 2009;55:1251-65.

8. Heidenreich A, Ohlmann CH, Polyakov S. Anatomical extent of pelvic lymphadenectomy in patients undergoing radical prostatectomy. Eur Urol 2007;52:29-37.

9. Masterson TA, Bianco FJ Jr, Vickers AJ, DiBlasio CJ, Fearn PA, Rabbani F, et al. The association between total and positive lymph node counts, and disease progression in clinically localized prostate cancer. J Urol 2006;175:1320-4; discussion 1324-5.

10. Allaf ME, Palapattu GS, Trock BJ, Carter HB, Walsh PC. Anatomical extent of lymph node dissection: impact on men with clinically localized prostate cancer. J Urol 2004;172:1840-4.

11. Joslyn SA, Konety BR. Impact of extent of lymphadenectomy on survival after radical prostatectomy for prostate cancer. Urology 2006;68:121-5.

12. Bader P, Burkhard FC, Markwalder R, Studer UE. Disease progression and survival of patients with positive lymph nodes after radical prostatectomy. Is there a chance of cure? J Urol 2003;169:849-54.

13. Wagner M, Sokoloff M, Daneshmand S. The role of pelvic lymphadenectomy for prostate cancer--therapeutic? J Urol 2008;179:408-13.

14. Daneshmand S, Quek ML, Stein JP, Lieskovsky G, Cai J, Pinski J, et al. Prognosis of patients with lymph node positive prostate cancer following radical prostatectomy: long-term results. J Urol 2004;172:2252-5.

15. Briganti A, Larcher A, Abdollah F, Capitanio U, Gallina A, Suardi N, et al. Updated nomogram predicting lymph node invasion in patients with prostate cancer undergoing extended pelvic lymph node dissection:the essential importance of percentage of positive cores. Eur Urol 2012;61: 480-7.

16. Dell’Oglio P, Abdollah F, Suardi N, Gallina A, Cucchiara V, Vizziello D, et al. External validation of the European association of urology recommendations for pelvic lymph node dissection in patients treated with robot-assisted radical prostatectomy. J Endourol 2014;28: 416-23.

17. Hinev AI, Anakievski D, Kolev NH, Hadjiev VI. Validation of nomograms predicting lymph node involvement in patients with prostate cancer undergoing extended pelvic lymph node dissection. Urol int 2014;92:300-5.

18. Mandel P, Kriegmair MC, Veleva V, Salomon G, Graefen M, Huland H, et al. The role of pelvic lymph node dissection during radical prostatectomy in patients with Gleason 6 intermediate-risk prostate cancer. Urology 2016;93:141-6.

19. Fossati N, Willemse PM, Van den Broeck T, van den Bergh RCN, Yuan CY, Briers E, et al. The benefits and harms of different extents of lymph node dissection during radical prostatectomy for prostate cancer: a systematic review. Eur Urol 2017;72:84-109.

==근거표==

{| class="wikitable"
!KQ9
!
|-
!Reference
|1. 1. Clark T, Parekh DJ, Cookson MS, Chang SS, Smith ER Jr, Wells N, et al. Randomized prospective evaluation of extended versus limited lymph node dissection in patients with clinically localized prostate cancer. J Urol 2003;169:145-7.
|-
!Study type
|Randomized prospective study.
|-
!Patients
|123 patients undergoing radical prostatectomy
|-
!Purpose of Study
|To assess the value of an extended node dissection in detecting nodal metastasis
|-
!Study Results
|Mean patient age was 61 years. Clinical stage was T1c in 88 patients (72%), T2a in 26 (21%), T2b in 7 (6%) and T3 in 2 (1%). Mean preoperative prostate specific antigen was 7.4 ng./ml. Pelvic lymph node metastasis was histologically confirmed in 8 patients (6.5%). Positive nodes were found on the side of the extended dissection in 4 patients, on the side of the limited dissection in 3 and on both sides in 1. Complications possibly attributable to the node dissection included lymphocele in 4 patients, lower extremity edema in 5, deep venous thrombosis in 2, ureteral injury in 1 and pelvic abscess in 1. These complications occurred 3 times more often on the side of the extended dissection (p=0.08).
|-
!Level of Study
|1
|-
!Reference
|2. Briganti A, Giannarini G, Karnes RJ, Gandaglia G, Ficarra V, Montorsi F. What evidence do we need to support the use of extended pelvic lymph node dissection in prostate cancer? Eur Urol 2015;67:597-8.
|-
!Study type
|Expert opinion
|-
!Patients
|
|-
!Purpose of Study 
|To discuss the role of pelvic lymph node dissection (PLND) at the time of radical prostatectomy (RP)
|-
!Study Results
|Even a prospective randomised trial might not provide a definitive answer as to the key clinical questions concerning the role of PLND at the time of RP, and might potentially lead to misleading conclusions. So what should we do? Knowledge of the biology of the disease should inform us on the type of treatment we should offer to our patients, and not vice versa. In this regard, novel biomarkers and genetic signatures may certainly help in closing this gap.
|-
!Level of Study
|6
|-
!Reference
|3. Briganti A, Abdollah F, Nini A, Suardi N, Gallina A, Capitanio U, et al. Performance characteristics of computed tomography in detecting lymph node metastases in contemporary patients with prostate cancer treated with extended pelvic lymph node dissection. Eur Urol 2012;61:1132-8.
|-
!Study type
|Retrospective study
|-
!Patients
|1541 patients undergoing radical prostatectomy and ePLND between 2003 and 2010 at a single center.
|-
!Purpose of Study
|To assess the value of CT in predicting LNI in contemporary PCa patients treated with extended PLND (ePLND).
|-
!Study Results
|Overall, a CT scan that suggested LNI was found in 73 patients (4.7%). Of them, only 24 patients (32.8%) had histologically proven LNI at ePLND. Overall, sensitivity, specificity, and accuracy of CT scan were 13%, 96.0%, and 54.6%, respectively. In patients with low-, intermediate-, or high-risk PCa according to NCCN classification, sensitivity was 8.3%, 96.3%, and 52.3%, respectively; specificity was 3.6%, 97.3%, and 50.5%, respectively; and accuracy was 17.9%, 94.3%, and 56.1%, respectively. Similarly, in patients with a nomogram-derived LNI risk ≥ 50%, sensitivity, specificity, and accuracy were only 23.9%, 94.7%, and 59.3%, respectively. At multivariable analyses, inclusion of CT scan findings did not improve the accuracy of LNI prediction (81.4% compared with 81.3%; p=0.8). Lack of a central scan review represents the main limitation of our study.
|-
!Level of Study
|3
|-
!Reference
|4. Kim KH, Lim SK, Kim HY, Shin TY, Lee JY, Choi YD, et al. Extended vs standard lymph node dissection in robot-assisted radical prostatectomy for intermediate- or high-risk prostate cancer: a propensity-score-matching analysis. BJU Int 2013;112:216-23.
|-
!Study type
|Retrospective study
|-
!Patients
|905 patients underwent robot-assisted radical prostatectomy and lymph node dissection (LND) by a single surgeon between June 2006 and January 2011
|-
!Purpose of Study
|To To compare the pathological and biochemical outcomes between extended lymph node dissection (eLND) and standard lymph node dissection (sLND) in patients undergoing robot-assisted radical prostatectomy for intermediate- or high-risk prostate cancer.
|-
!Study Results
|The median (range) follow-up period was 36 (12-77) months and the median number of lymph nodes removed was 21 and 12 in the eLND and sLND groups, respectively. Propensity-score matching resulted in 141 patients in each group. Although patients who underwent eLND had a higher clinical stage, biopsy Gleason score and number of positive cores than those treated with sLND in the entire cohort, there were no preoperative between-group differences in the matched cohort. In the matched cohort, lymph node metastases were detected at a significantly higher rate in the eLND than in the sLND group (12.1 vs. 5.0%, P=0.033). In the matched cohort, the 3-year biochemical recurrence-free survival rates were 77.8 and 73.5% in the eLND and sLND groups, respectively, which was not significant (hazard ratio 0.85, P=0.497).
|-
!Level of Study
|3
|-
!Reference
|5. Choi D, Kim D, Kyung YS, Lim JH, Song SH, You D, et al. Clinical experience with
limited lymph node dissection for prostate cancer in Korea: single center comparison of 247 open and 354 robot-assisted laparoscopic radical prostatectomy series. Korean J Urol 2012;53:755-60.
|-
!Study type
|Retrospective study
|-
!Patients
|601 consecutive patients undergoing radical prostatectomy and bilateral limited PLND by either RRP (n=247) or RALP (n=354) in Asan Medical Center.
|-
!Purpose of Study
|To demonstrate our clinical experience with limited PLND and the difference in its yield between open retropubic radical prostatectomy (RRP) and robot-assisted laparoscopic radical prostatectomy (RALP) for prostate cancer patients in Korea.
|-
!Study Results
|The mean patient age was 64.9 years and the mean preoperative prostate-specific antigen was 9.8 ng/ml. The median number of removed lymph nodes per patient was 5 (range, 0 to 20). The numbers of patients of each risk group were 167, 199, and 238, and the numbers of patients with tumor-positive lymph nodes were 1 (0.6%), 4 (2.0%), and 17 (7.1%) in the low-, intermediate-, and high-risk groups, respectively. In the high-risk group, the lymph node-positive ratio was higher in RRP (14.9%) than in RALP subjects (2.4%).
|-
!Level of Study
|3
|-
!Reference
|6. Cagiannos I, Karakiewicz P, Eastham JA, Ohori M, Rabbani F, Gerigk C, et al. A
preoperative nomogram identifying decreased risk of positive pelvic lymph nodes in patients with prostate cancer. J Urol 2003;170:1798-803. 
|-
!Study type
|Retrospective study
|-
!Patients
|7,014 patients treated with radical prostatectomy at 6 institutions between 1985 and 2000.
|-
!Purpose of Study
|To develope a preoperative nomogram for prediction of lymph node metastases in patients with clinically localized prostate cancer.
|-
!Study Results
|Overall 5,510 patients with complete clinical and pathological information were included in the study. Lymph nodes metastases were present in 206 patients (3.7%). Pretreatment PSA, biopsy Gleason sum, clinical stage and institution represented predictors of lymph node status (p<0.001). Bootstrap corrected predictive accuracy of the 3-variable nomogram (clinical stage, Gleason sum and PSA) was 0.76. Inclusion of a fourth variable, which accounts for institutional differences in lymph node metastases, yielded an area under the receiver operating characteristics curve of 0.78. The negative predictive value of our nomograms was 0.99 when they predicted 3% or less chance of positive lymph nodes.
|-
!Level of Study
|3
|-
!Reference
|7. Briganti A, Blute ML, Eastham JH, Graefen M, Heidenreich A, Karnes JR, et al. Pelvic lymph node dissection in prostate cancer. Eur Urol 2009;55:1251-65. 
|-
!Study type
|Systematic review
|-
!Patients
| 
|-
!Purpose of Study
|To systematically review the available literature concerning the role of PLND and its extent in PCa staging and outcome.
|-
!Study Results
|Despite recent advances in imaging techniques, PLND remains the most accurate staging procedure for the detection of lymph node invasion (LNI) in PCa. The rate of LNI increases with the extent of PLND. Extended PLND (ePLND; ie, removal of obturator, external iliac, hypogastric with or without presacral and common iliac nodes) significantly improves the detection of lymph node metastases compared with limited PLND (lPLND; ie, removal of obturator with or without external iliac nodes), which is associated with poor staging accuracy. Because not all patients with PCa are at the same risk of harbouring nodal metastases, several nomograms and tables have been developed and validated to identify candidates for PLND. These tools, however, are based mostly on findings derived from lPLND dissections performed in older patient series. According to these prediction models, a staging PLND might be omitted in low-risk PCa patients because of the low rate of lymph node metastases found, even after extended dissections (<8%). The outcome for patients with positive nodes is not necessarily poor. Indeed, patients with low-volume nodal metastases experience excellent survival rates, regardless of adjuvant treatment. But despite few retrospective studies reporting an association between PLND and PCa progression and survival, the exact impact of PLND on patient outcomes has not yet been clearly proven because of the lack of prospective randomised trials.
|-
!Level of Study
|1
|-
!Reference
|8. Heidenreich A, Ohlmann CH, Polyakov S. Anatomical extent of pelvic lymphadenectomy in patients undergoing radical prostatectomy. Eur Urol 2007;52:29-37. 
|-
!Study type
|Systematic review
|-
!Patients
| 
|-
!Purpose of Study
|To critically evaluate the current status on PLND in prostate cancer
|-
!Study Results
|The anatomical lymphatic drainage of the prostate includes the obturator fossa, and the external and internal iliac arteries; therefore, at least these areas should be included in PLND. According to the current clinical studies, extended PLND (ePLND) significantly increases the yield of both total lymph nodes and lymph node metastases independent of the risk classification of pCA. Lymph node metastases will be detected in about 5-6%, 20-25%, and 30-40% of low-, intermediate-, and high-risk pCA, respectively. Exclusively 25% of all positive lymph nodes are located in the area around the internal iliac artery. With regard to progression-free and cancer-specific survival, retrospective analysis of the SEER
data and additional case-control studies indicate a direct positive relationship between the number of removed lymph nodes and long-term oncological outcome in patients with limited lymph node involvement or negative lymph nodes. In these patients, cancer-specific survival is improved by about 15-20%. On the basis of results of large case-control studies, complication rates of ePLND are not significantly increased.
|-
!Level of Study
|1
|-
!Reference
|9. Masterson TA, Bianco FJ Jr, Vickers AJ, DiBlasio CJ, Fearn PA, Rabbani F, et al. The association between total and positive lymph node counts, and disease progression in clinically localized prostate cancer. J Urol 2006;175:1320-4; discussion 1324-5. 
|-
!Study type
|Retrospective study
|-
!Patients
|5,038 patients who underwent radical retropubic prostatectomy between 1983 and 2003.
|-
!Purpose of Study
|To examine the association between the number of LNs removed, the number of positive LNs and disease progression in patients undergoing pelvic lymph node dissection and radical retropubic prostatectomy for clinically localized prostate cancer.
|-
!Study Results
|The 4,611 eligible patients had a median of 9 LNs (IQR 5 to 13) removed. Positive nodes were found in 175 patients (3.8%). Overall the number of LNs removed did not predict freedom from BCR (HR per additional 10 nodes removed 1.02, 95% CI 0.92 to 1.13, p=0.7). Results were similar in patients receiving and not receiving neoadjuvant hormonal therapy. Finding any LN involvement was associated with a BCR HR of 5.2 (95% CI 4.2 to 6.4, p<0.0005). However, in men without nodal involvement an increased number of nodes removed correlated significantly with freedom from BCR (p=0.01).
|-
!Level of Study
|3
|-
!Reference
|10. Allaf ME, Palapattu GS, Trock BJ, Carter HB, Walsh PC. Anatomical extent of
lymph node dissection: impact on men with clinically localized prostate cancer. J Urol 2004;172:1840-4. 
|-
!Study type
|Retrospective study
|-
!Patients
|2,135 patients (RP + ePLND) and 1,865 patients (RP + limited PLND)
|-
!Purpose of Study
|To evaluate the influence of the anatomical extent of pelvic lymph node dissection
performed at radical prostatectomy on lymph node yield, staging accuracy and time to prostate specific antigen progression.

|-
!Study Results
|Extended lymph node dissection removed more lymph nodes (mean 11.6 vs 8.9,
p<0.0001) and detected more lymph node positive disease (3.2% vs 1.1%, p<0.0001) than the more anatomically limited technique. This finding held true for patients across all pathology groups. Among men with lymph node positive disease involving less than 15% of extracted nodes, the 5-year prostate specific antigen progression-free rate for extended lymph node dissection was 43% versus 10% for the more limited lymph node dissection (p=0.01).
|-
!Level of Study
|3
|-
!Reference
|11. Joslyn SA, Konety BR. Impact of extent of lymphadenectomy on survival after radical prostatectomy for prostate cancer. Urology 2006;68:121-5. 
|-
!Study type
|Retrospective study
|-
!Patients
|13,020 patients who underwent radical prostatectomy (with or without lymphadenectomy) for prostate cancer obtained from the Surveillance, Epidemiology, and End Results Program (1988 to 1991).
|-
!Purpose of Study
|To determine whether more extended lymphadenectomy, along with radical prostatectomy, resulted in a decreased risk of prostate cancer-specific death at 10 years
|-
!Study Results
|Patients undergoing excision of at least 4 lymph nodes (node-positive and node-negative patients) or more than 10 nodes (only node-negative patients) had a lower risk of prostate cancer-specific death at 10 years than did those who did not undergo lymphadenectomy. The removal of a greater number of nodes was associated with a greater likelihood of the presence of positive nodes. The presence of more than one positive node was associated with a greater risk of prostate cancer-related death.
|-
!Level of Study
|3
|-
!Reference
|12. Bader P, Burkhard FC, Markwalder R, Studer UE. Disease progression and survival of patients with positive lymph nodes after radical prostatectomy. Is there a chance of cure? J Urol 2003;169:849-54. 
|-
!Study type
|Retrospective study
|-
!Patients
|367 patients with clinically organ confined prostate cancer underwent meticulous pelvic lymph node dissection and radical prostatectomy.
|-
!Purpose of Study
|To determine progression rate and survival of patients with positive nodes following radical prostatectomy according to the number of metastases
|-
!Study Results
|Of the patients 92 (25%) had histologically proven lymph node metastases. Followup of more than 1 year was available in 88 patients (96%), and median followup was 45 months (range 13 to 141). Of 19 patients (22%) who died of prostate cancer 16 had more than 1 positive node. Of the 39 patients with only 1 positive node 15 (39%) remained without signs of clinical or chemical progression. Whereas of the 20 and 29 patients with 2 or more positive lymph nodes only 2 (10%) and 4 (14%), respectively, remained disease-free. Time to prostate specific antigen relapse, symptomatic progression and tumor related death were significantly affected by the number of positive nodes
|-
!Level of Study
|3
|-
!Reference
|13. Wagner M, Sokoloff M, Daneshmand S. The role of pelvic lymphadenectomy for prostate cancer--therapeutic? J Urol 2008;179:408-13. 
|-
!Study type
|Systematic review
|-
!Patients
| 
|-
!Purpose of Study
|To analyze the current literature on the role of pelvic lymphadenectomy in prostate cancer.
|-
!Study Results
|Staging pelvic lymphadenectomy provides valuable prognostic data and it may be therapeutic. Extended lymph node dissection increases the detection of positive nodes. The number of positive or negative nodes resected may increase survival. The observed survival benefits may be due to the elimination of micrometastatic disease
|-
!Level of Study
|1
|-
!Reference
|14. Daneshmand S, Quek ML, Stein JP, Lieskovsky G, Cai J, Pinski J, et al. Prognosis of patients with lymph node positive prostate cancer following radical prostatectomy: long-term results. J Urol 2004;172:2252-5. 
|-
!Study type
|Retrospective study
|-
!Patients
|1,936 patients who underwent radical retropubic prostatectomy and pelvic lymph node dissection for clinically organ confined prostate cancer.
|-
!Purpose of Study
|To determine the prognostic factors that affect recurrence and survival in patients with lymph node positive prostate cancer.
|-
!Study Results
|Followup was 1 to 24 years (median 11.4). Overall median survival was 15 years.
Overall clinical recurrence-free survival at 5, 10 and 15 years was 80%, 65% and 58%, respectively. Patients who had 1 or 2 positive lymph nodes had a clinical recurrence-free survival of 70% and 73% at 10 years, respectively, vs 49% in those who had 5 or more involved lymph nodes (p=0.0031). When stratified by lymph node density, patients with a lymph node density of 20% or greater were at higher risk for clinical recurrence compared to those with a density of less than 20% (relative risk=2.32, p<0.0001). On stratified log rank test only prostate cancer T stage, and the number and percent of positive lymph nodes correlated with recurrence-free and overall survival.
|-
!Level of Study
|3
|-
!Reference
|15. Briganti A, Larcher A, Abdollah F, Capitanio U, Gallina A, Suardi N, et al. Updated nomogram predicting lymph node invasion in patients with prostate cancer undergoing extended pelvic lymph node dissection: the essential importance of percentage of positive cores. Eur Urol 2012;61:480-7. 
|-
!Study type
|Retrospective study
|-
!Patients
|588 patients with clinically localised PCa
|-
!Purpose of Study
|To update a nomogram predicting the presence of LNI in patients treated with ePLND at the time of radical prostatectomy (RP).
|-
!Study Results
|The mean number of lymph nodes removed and examined was 20.8 (median: 19; range: 10-52). LNI was found in 49 of 588 patients (8.3%). All preoperative PCa characteristics differed significantly between LNI-positive and LNI-negative patients (all p<0.001). In UVA predictive accuracy analyses, percentage of positive cores was the most accurate predictor of LNI (AUC: 79.5%). At MVA, clinical stage, primary biopsy Gleason grade, and percentage of positive cores were independent predictors of LNI (all p≤0.006). The updated nomogram demonstrated a bootstrap-corrected PA of 87.6%. Using a 5% nomogram cut-off, 385 of 588 patients (65.5%) would be spared ePLND. and LNI would be missed in
only 6 patients (1.5%). The sensitivity, specificity, and negative predictive value associated with the 5% cut-off were 87.8%, 70.3%, and 98.4%, respectively
|-
!Level of Study
|3
|-
!Reference
|16. Dell’Oglio P, Abdollah F, Suardi N, Gallina A, Cucchiara V, Vizziello D, et al. External validation of the European association of urology recommendations for pelvic lymph node dissection in patients treated with robot-assisted radical prostatectomy. J Endourol 2014;28:416-23. 
|-
!Study type
|Retrospective study
|-
!Patients
|615 patients treated with RARP and PLND
|-
!Purpose of Study
|To specifically assess the accuracy of the EAU recommendation for PLND among men treated with robot-assisted radical prostatectomy (RARP).
|-
!Study Results
|Median of lymph nodes (LNs) removed was 9 (interquartile range: 6-13). The rate of LNI was 5%. External validation of the Briganti nomogram showed good accuracy (81.8%). A nomogram-derived cutoff of 5% would allow the avoidance of 75% of PLND at the cost of missing of 19.4% of patients with LNI. When the same analyses were repeated in men with at least 10 and 15 LNs removed, the 5% cutoff was associated with a reduction in PLND and with an LNI missing rates of 67.6% and 59.3% and 17.4% and 6.2%, respectively. Similarly, the prediction accuracy increased to 81.2% and 85.3%, respectively. The decision curve analysis showed an increase in the net-benefit in the prediction range between 2.5% and 54%.
|-
!Level of Study
|3
|-
!Reference
|17. Hinev AI, Anakievski D, Kolev NH, Hadjiev VI. Validation of nomograms predicting lymph node involvement in patients with prostate cancer undergoing extended pelvic lymph node dissection. Urol int 2014;92:300-5. 
|-
!Study type
|Retrospective study
|-
!Patients
|256 PCa patients who underwent extended pelvic lymph node dissection (ePLND) and radical prostatectomy (RP) were obtained from two Bulgarian institutions
|-
!Purpose of Study
|To validate Briganti’s nomograms predicting the probability of lymph node involvement (LNI) in prostate cancer (PCa).
|-
!Study Results
|All of Briganti’s nomograms showed a higher predictive accuracy as compared with the updated MSKCC nomogram. The respective AUC values were calculated as 0.847, 0.837, 0.858 and 0.875 for the four Briganti nomograms, and 0.770 for the updated MSKCC nomogram, respectively. Despite the potential for heterogeneity in patient selection and management, all predictions demonstrated high concordance with actual observations. Compared with other similar prognostic tools the updated Briganti nomogram (version 2012) showed the highest predictive accuracy and should therefore be preferred
|-
!Level of Study
|3
|-
!Reference
|18. Mandel P, Kriegmair MC, Veleva V, Salomon G, Graefen M, Huland H, et al. The role of pelvic lymph node dissection during radical prostatectomy in patients with Gleason 6 intermediate-risk prostate cancer. Urology 2016;93:141-6. 
|-
!Study type
|Retrospective study
|-
!Patients
|1,383 patients with low intermediate-risk cancer (biopsy Gleason grade ≤6, cT ≤2b, and prostate-specific antigen (PSA) 10-20 ng/mL) undergoing radical prostatectomy with or without PLND
|-
!Purpose of Study
|To analyze the benefit of pelvic lymph node dissection (PLND) in patients with biopsy Gleason grade ≤6, cT ≤2b, and prostate-specific antigen (PSA) 10-20 ng/mL.
|-
!Study Results
|In the main study cohort (PSA 10-20 ng/mL), PLND was performed in 867 (62.7%)
patients with a median number of removed LNs of 11 (interquartile range 16-6). Positive LNs were detected in 3.3% of these patients. Compared to the main study cohort, patients with preoperatively higher PSA ≥20 ng/mL (or lower PSA <10 ng/ml) underwent PLND in 83.8% (32.7%) of the cases, with 8.0% (1.8%) showing positive LNs. Median follow-up in the main study cohort was 84.5 months. Biochemical recurrence (BCR) occurred in 20.6% of these men. The 5-year and 10-year BCR-free survival rates were 82.2% and 75.6% for those with PLND, and 83.4% and 75.8% for patients without PLND. PLND was not a significant factor influencing BCR-free, metastasis-free, or cancer-specific survival in the main study cohort.
|-
!Level of Study
|3
|-
!Reference
|19. Fossati N, Willemse PM, Van den Broeck T, van den Bergh RCN, Yuan CY, Briers E, et al. The benefits and harms of different extents of lymph node dissection during radical prostatectomy for prostate cancer: a systematic review. Eur Urol 2017;72:84-109. 
|-
!Study type
|systematic review
|-
!Patients
|66 studies recruiting a total of 275,269 patients were included (44 full-text articles and 22 conference abstracts)
|-
!Purpose of Study
|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.
|-
!Study Results
|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.
|-
!Level of Study
|1
|-