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Clinical Research Papers:

Robotic vs. Retropubic radical prostatectomy in prostate cancer: A systematic review and a meta-analysis update

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Oncotarget. 2017; 8:32237-32257. https://doi.org/10.18632/oncotarget.13332

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Kun Tang, Kehua Jiang, Hongbo Chen, Zhiqiang Chen, Hua Xu _ and Zhangqun Ye

Abstract

Kun Tang1,*, Kehua Jiang1,2,*, Hongbo Chen2, Zhiqiang Chen1, Hua Xu1 and Zhangqun Ye1

1 Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

2 Department of Urology, The Central Hospital of Enshi Autonomous Prefecture, Enshi, China

* These authors have contributed equally to this work

Correspondence to:

Hua Xu, email:

Keywords: robotic-assisted radical prostatectomy; retropubic radical prostatectomy; prostate cancer; meta-analysis; update

Received: February 18, 2016 Accepted: October 21, 2016 Published: November 12, 2016

Abstract

CONTEXT: The safety and feasibility of robotic-assisted radical prostatectomy (RARP) compared with retropubic radical prostatectomy(RRP) is debated. Recently, a number of large-scale and high-quality studies have been conducted.

OBJECTIVE: To obtain a more valid assessment, we update the meta-analysis of RARP compared with RRP to assessed its safety and feasibility in treatment of prostate cancer.

METHODS: A systematic search of Medline, Embase, Pubmed, and the Cochrane Library was performed to identify studies that compared RARP with RRP. Outcomes of interest included perioperative, pathologic variables and complications.

RESULTS: 78 studies assessing RARP vs. RRP were included for meta-analysis. Although patients underwent RRP have shorter operative time than RARP (WMD: 39.85 minutes; P < 0.001), patients underwent RARP have less intraoperative blood loss (WMD = -507.67ml; P < 0.001), lower blood transfusion rates (OR = 0.13; P < 0.001), shorter time to remove catheter (WMD = -3.04day; P < 0.001), shorter hospital stay (WMD = -1.62day; P < 0.001), lower PSM rates (OR:0.88; P = 0.04), fewer positive lymph nodes (OR:0.45;P < 0.001), fewer overall complications (OR:0.43; P < 0.001), higher 3- and 12-mo potent recovery rate (OR:3.19;P = 0.02; OR:2.37; P = 0.005, respectively), and lower readmission rate (OR:0.70, P = 0.03). The biochemical recurrence free survival of RARP is better than RRP (OR:1.33, P = 0.04). All the other calculated results are similar between the two groups.

CONCLUSIONS: Our results indicate that RARP appears to be safe and effective to its counterpart RRP in selected patients.


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Introduction

Prostate cancer (PCa) is the most common cancer in the worldwide and its morbidity,mortality is the first and second common cancer in men, respectively [1]. RP is the standard therapy for patients with localized PCa [2]. However, open retropubic radical prostatectomy (RRP) is associated with higher overall complications, including estimated blood loss (EBL), wound infections. With the development of surgical techniques, laparoscopic techniques and robot assisted surgeries have become a very popular procedure for the management of urological disease throughout the world [3]. Compared with RRP, the advantages of laparoscopic radical prostatectomy (LRP) are less EBL, fewer complications, better cosmetic effect and shorter hospital stay [4]. The disadvantages of LRP is lack of 3D visualization and poor ergonomics.

As alternatives to open surgery, RARP has became a predominant procedure for the treatment the localized prostate cancer in the world [5]. Assessing of the robotic surgery by expert indicate better ergonomics and quicker learning curve, but its shortage is high cost of the robotic surgery system.

In recent years, many experts have reported on comparative study of RARP and open RRP. And some meta-analysis were performed to evaluate the advantages and disadvantages of two approaches, including perioperative outcomes, oncologic outcomes [5]. Their early experience showed that the outcomes of this approach with fewer overall complications, quicker convalescence, and lower EBL and transfusion [5-7]. However, the outcomes of RARP compared with RRP have not been fully evaluated, and no conclusive results are available. Therefore, a systematic review and meta-analysis of the included published studies was performed to compare RARP with RRP.

Results

Characteristics of eligible studies

According to search strategy, the included 78 studies [4, 8-85] assessing RARP vs. RRP met the inclusion criteria and were applied to perform this meta-analysis (Figure 1). Those studies include forty-three retrospective and thirty-five prospective studies and were listed in Table 1.

Quality of the studies and level of evidence (Table 1)
In this meat-analysis, the Newcastle-Ottawa Scale quality assessment method of the observational studies [86], and the US Preventive Services Task Force grading system [87] were applied to evaluate the quality of included studies. Twenty studies scored seven stars and were evaluated as the high quality studies. Additionally, The clinical variables of RARP and RRP were extracted independently from included literatures (Table 1).

Table 1: Characteristics of included studies

First author, year

Country

Study interval

Design

LOE

No.of patients

RARP/RRP

Matching/

comparable*

Quality scoreΔ

Ahlering, 2004

USA

2001-2002

Prospective

3b

60/60

1, 2, 3, 4

*****

Bae, 2012

Korea

2008-2011

Retrospective

3b

111/70

1, 2, 3, 4, 5, 6

*******

Ball, 2006

USA

2000-2005

Prospective

3b

82/135

1, 3, 5, 6

*****

Barocas, 2010

USA

2003-2008

Prospective

3b

1413/491

1, 3, 7

*****

Bolenz, 2010

USA

2003-2008

Retrospective

3b

262/161

1, 2, 3, 4, 6

******

Breyer, 2010

USA

2002-2008

Prospective

3b

293/695

1, 3, 4, 5, 6, 7

*******

Carlsson, 2010

Sweden

2002-2007

Prospective

3b

1253/485

1, 3, 4, 5,

*****

Chan, 2008

USA

2003-2006

Retrospective

3b

660/340

1, 3, 5, 6

*****

Chino, 2009

USA

2003-2007

Retrospective

3b

368/536

1, 3, 5, 6

*****

Choi, 2012

Korea

2007-2011

Retrospective

3b

354/247

1, 3, 5

****

Choo, 2013

Korea

2003-2010

Prospective

3b

77/176

1, 2, 3, 4, 5, 6, 7

*******

Chung, 2012

Taiwan

2006-2009

Retrospective

4

274/1773

1, 7

****

D'Alonzo, 2009

USA

2003-2006

Retrospective

3b

256/280

1, 2, 3, 4, 7

******

Di Pierro, 2011

Switzerland

2007-2009

Prospective

3b

75/75

1, 3, 5, 6, 7

*****

Doumerc, 2010

France

2006-2008

Prospective

3b

212/502

1, 3, 4, 5, 6, 7

*******

Drouin, 2009

France

2000-2004

Retrospective

3b

71/83

1, 2, 3, 5, 6, 7

*******

Farnham, 2006

USA

2003-2004

Prospective

3b

176/103

1, 3, 4, 6

*****

Ficarra, 2009

Italy

2006-2007

Prospective

3b

103/105

1, 2, 3, 4, 5, 6, 7

*******

Fracalanza, 2008

Italy

2006

Prospective

3b

35/26

1, 2, 3, 4, 6

******

Forehner, 2013

Germany

2007-2011

Prospective

3b

252/1925

1, 3, 6, 7

*****

Hong, 2010

Korea

2007

Retrospective

4

26/25

1, 2, 7

****

Park, 2014

Korea

2007-2012

Retrospective

3b

730/277

1, 2, 3, 4, 5, 6, 7

*******

Busch, 2015

Germany

NA

Prospective

3b

194/194

1, 3, 5, 6

*****

Kim, 2011

Korea

2007-2010

Prospective

3b

528/235

1, 2, 3, 5, 6, 7

******

Kordan, 2010

USA

2003-2006

Prospective

3b

830/414

1, 2, 3, 5, 6

*****

Krambeck, 2008

USA

2002-2005

Prospective

3b

294/588

1, 2, 3, 5, 6, 7

*******

Laurila, 2009

USA

2006

Retrospective

3b

94/98

1, 3, 5, 6

*****

Lo, 2010

HongKong

2006-2007

Retrospective

3b

20/20

1, 3, 5, 6, 7

*****

Magheli, 2011

USA

2000-2008

Prospective

3b

522/522

1, 3, 4, 5, 6, 7

*****

Malcolm, 2010

USA

2000-2008

Retrospective

3b

477/135

1, 3, 5, 6, 7

*****

Menon, 2002

France

2001

Prospective

3b

30/30

1, 3, 4, 5, 6, 7

*******

Miller, 2007

USA

2002-2006

Prospective

4

42/120

1

****

Minniti, 2011

Italy

2007-2008

Prospective

3b

22/93

1, 2, 3, 5

****

Nelson, 2007

USA

2003-2006

Prospective

3b

629/374

1, 3, 6

*****

OU, 2009

Taiwan

2004-2007

Retrospective

3b

30/30

1, 2, 3, 4, 5, 6

*******

Pilecki, 2014

USA

2011

Retrospective

4

4374/1097

1, 2

****

Rocco, 2009

Italy

2004-2007

Prospective

3b

120/240

1, 3, 5, 6, 7

******

Ryu, 2013

Korea

2007-2012

Prospective

4

524/341

1, 2, 3, 4

*****

Schroeck, 2008

USA

2003-2007

Retrospective

3b

362/435

1, 2, 3, 4, 5, 6, 7

*******

Shapiro, 2014

USA

2000-2010

Retrospective

3b

108/229

1, 3, 5, 6, 7

*****

Silberstein, 2012

USA

2010

Retrospective

4

126/126

1, 3, 5, 6

*****

Smith, 2007

USA

2002-2006

Retrospective

3b

200/200

1, 2, 3, 4, 5, 6

*******

Son, 2013

Korea

2006-2009

Retrospective

3b

146/112

1, 2, 3, 4, 6, 7

******

Stranne, 2010

Sweden

2002-2006

Retrospective

3b

946/465

1, 2, 3, 4, 5, 6, 7

*******

Sugihara, 2014

Japan

2012-2013

Retrospective

3b

2126/7202

1, 2, 5,

****

Tewari, 2003

USA

1999-2002

Prospective

3b

200/100

1, 2, 3, 4, 5, 6, 7

*******

Truesdale, 2010

USA

2005-2009

Retrospective

3b

99/217

1, 2, 3, 5, 6

******

Vora, 2013

USA

1997-2010

Retrospective

3b

140/95

1, 3, 5, 6, 7

*****

White, 2009

USA

2005-2008

Retrospective

3b

50/50

1, 3, 5, 6

*****

Williams, 2010

USA

2005-2008

Retrospective

4

604/346

1, 3, 5, 6

*****

Wood, 2007

USA

2003-2005

Prospective

4

165/152

1, 3, 7

*****

Yi, 2010

Korea

2006-2009

Retrospective

3b

153/641

1, 2, 3, 6, 7

*****

Rush, 2015

Canada

2009-2012

Retrospective

3b

331/643

1, 2, 3, 4, 7

*****

Ong, 2015

Australian

2009-2012

Prospective

3b

885/1117

1, 3, 5, 6, 7

******

Porcaro, 2015

Italy

2013

Retrospective

4

108/43

1, 2, 3, 4, 5, 6, 7

*******

O'Neil, 2015

USA

2011-2012

Prospective

3b

933/1505

1, 3, 6, 7

****

Niklas, 2015

Germany

2003-2010

Retrospective

3b

932/499

1, 2, 3, 4, 5, 6, 7

*******

Haglind, 2015

Sweden

2008-2011

Prospective

3b

1847/778

1, 2, 3, 5, 6

******

Gagnon, 2014

Canada

NA

Retrospective

3b

200/200

1, 2, 3, 4, 5, 6, 7

******

Davison, 2014

Canada

2007-2009

Prospective

3b

78/73

1, 3, 5

*****

Akand, 2015

Turkey

1999-2012

Retrospective

4

79/50

1, 2, 3, 4, 5, 7

******

Korets, 2014

USA

2007-2012

Retrospective

3b

12746/3398

1, 2, 7

*****

Wallerstedt, 2015

Sweden

NA

Prospective

3b

1847/778

1, 2, 3, 5, 6, 7

******

Hu, 2015

USA

2004-2009

Retrospective

3b

5524/7878

1, 2, 3, 5, 6, 7

******

Davis, 2014

USA

2004-2010

Prospective

3b

27348/13840

1, 7

****

Rithch, 2014

USA

2003-2009

Retrospective

3b

742/237

1, 2, 3, 5, 6, 7

******

Gandaglia, 2014

USA

2008-2009

Retrospective

3b

3476/2439

1, 3, 5, 6, 7

*****

Koo, 2014

Korea

1992-2008

Retrospective

3b

175/175

1, 3, 5, 6, 7

******

Busch, 2014

Germany

NA

Retrospective

3b

110/110

1, 2, 3, 4, 5, 6, 7

*******

Alemozaffar, 2015

USA

2000-2010

Prospective

3b

282/621

1, 2, 3, 4, 5, 6, 7

*******

Harty, 2013

USA

2000-2010

Prospective

3b

152/153

1, 3, 4, 5, 6, 7

*******

Silberstein, 2013

USA

2007-2010

Retrospective

3b

493/961

1, 3, 5, 7

*****

Ludovico, 2013

Italy

2004-2008

Retrospective

3b

82/48

1, 3, 5, 6, 7

******

Musch, 2013

Germany

2009-2010

Retrospective

3b

105/105

1, 2, 3, 4, 5, 6, 7

******

Hall, 2014

Australia

2007-2009

Retrospective

3b

100/100

1, 3, 6

*****

Geraerts, 2013

Belgium

2009-2011

Prospective

3b

64/116

1, 2, 7

*****

Drouin, 2014

France

2007-2010

Prospective

3b

73/44

1, 3, 5, 6, 7

******

Pierorazio, 2013

USA

2002-2011

Retrospective

3b

105/743

1, 2, 3, 4, 5, 6, 7

*******

RARP=robot-assisted radical prostatectomy; RRP= retropubic radical prostatectomy; NA= data not available; LOE= level of evidence.

*:Matching/comparable variable: 1=age, 2=BMI, 3=PSA, 4=prostate size, 5=clinical stage, 6= biospy Gleason score, 7=follow up

Δ:based on Newcastle-Ottawa Scale.

PRISMA diagram.

Figure 1: PRISMA diagram. The search strategy and number of studies identified for inclusion in this meta-analysis.

Description of included studies and patients Demographics (Table 2)

Patients underwent RARP are younger (WMD = -1.00 years; 95% CI: -1.56 to -0.44; P < 0.001) (Figure S1), and have the lower level of pre-PSA (OR = -0.93; 95% CI: -1.47 to -0.40; P < 0.001) (Figure S2). But there is no significant difference on BMI (OR = -0.10; 95% CI: -0.39 to 0.20;P = 0.20) (Figure S3), and prostate volume (WMD = 2.35ml; 95% CI: -0.92 to 5.61; P = 0.16) (Figure S4) between the RARP and RRP group. (Table 2).

Table 2: Overall analysis of demographic and clinical characteristics compared RARP with RRP

Outcomes of interest

No. of studies

No. of patients

RARP/RRP

OR/WMD(95% CI )

p-value

Study heterogeneity

Chi2 df I2 p-value

Age(year)

33

41866/227181

-1.00[-1.56,-0.44]

<0.001

1260.51

32

97%

<0.001

BMI(kg/m2)

17

9365/4690

-0.10[-0.39,0.20]

0.52

87.93

16

82%

<0.001

Pre-PSA(ng/ml)

23

6161/5250

-0.93[-1.47,-0.40]

<0.001

234.69

22

91%

<0.001

Prostate volume(ml)

12

3995/3288

2.35[-0.92,5.61]

0.16

136.49

11

92%

<0.001

RARP=robot-assisted radical prostatectomy; RRP=retropubic radical prostatectomy; OR = odds ratio; WMD = weighted mean difference; CI = confidence interval; BMI = body mass index.

Outcomes of perioperative variables (Table 3)

Operating time and estimated blood loss (EBL)

With respect to perioperative variables, pooling data of 18 studies [21, 23, 24, 26, 29, 32, 34, 40, 54, 59, 60, 64, 70, 75, 78, 81, 84, 85] involving 54261 participants indicated that RARP has longer operative time than RRP (WMD: 39.85 minutes; 95% CI: 20.95 to 58.75; P < 0.001) (Figure 2). Pooling data of 13 studies [10, 21, 23, 29, 30, 34, 40, 60, 70, 75, 78, 84, 85] results showed that RARP has less intraoperative blood loss (WMD = -507.67ml; 95% CI: -633.21 to -382.12; P < 0.001) (Figure 3).

Table 3: Overall analysis of perioperative outcomes comparing RARP with RRP

Outcome of interest

No. of studies

No.of patients

RARP/RRP

OR/WMD(95%CI)

p-value

Study heterogeneity

Chi2 df I2 p-value

Operation time, min

18

36296/17965

39.85[20.95,58.75]

<0.001

2130.01

17

99%

<0.001

Estimated blood loss, ml

13

3446/2791

-507.67[-633.21,-382.12]

<0.001

390.34

12

97%

<0.001

Transfusion rate

26

54847/32967

0.13[0.08,0.21]

<0.001

693.85

25

96%

<0.001

Remove the catheter, day

5

2135/1264

-3.04[-4.59,-1.49]

<0.001

260.52

4

98%

<0.001

Hospital stay, day

11

32196/17106

-1.62[-2.42,-0.82]

<0.001

1517.19

10

99%

<0.001

RARP=robot-assisted radical prostatectomy; RRP=retropubic radical prostatectomy; OR = odds ratio; WMD = weighted mean difference; CI = confidence interval.

Table 4: Overall analysis of complications comparing RARP and RRP

Outcome of interest

No. of studies

No.of patients

RARP/RRP

OR (95%CI)

p-value

Study heterogeneity

Chi2 df I2 p-value

Overall complications

25

43087/28834

0.43 [0.32, 0.58]

<0.001

499.59

24

95%

<0.001

Rectal injury

8

3888/8110

0.16[0.07, 0.39]

<0.001

5.22

7

0%

0.63

Pulmonary embolism

9

37575/24635

0.47[0.37, 0.59]

<0.001

5.04

8

0%

0.75

Wound infections

10

11161/10587

0.23[0.11, 0.46]

<0.001

31.49

9

71%

<0.001

Bladder neck contracture

4

1993/2409

0.21[0.08,0.60]

0.003

8.39

3

64%

0.04

UTI

4

6586/2546

0.75[0.37,1.54]

0.44

15.35

3

80%

0.002

Urinary retention

3

2042/960

0.63[0.47,0.84]

0.002

2.44

2

18%

0.29

Obturator nerve injury

2

1453/585

0.09[0.01,0.75]

0.03

0.01

1

0%

0.91

DVT

7

7479/3072

0.40[0.25,0.66]

<0.001

10.82

6

45%

0.09

Urinary leakage

8

30940/15631

0.64[0.58,0.70]

<0.001

8.87

7

21%

0.26

ileus

8

3412/8501

0.92[0.56,1.51]

0.73

2.20

7

0%

0.95

lymphocele

9

45258/2639

0.52[0.29,0.94]

0.03

8.93

8

10%

0.35

Urinary continence-3mo

9

997/941

1.54[0.92,2.58]

0.10

22.06

8

64%

0.005

Urinary continence-12mo

9

1565/2179

1.03[0.84,1.27]

0.75

17.41

8

54%

0.03

Potent recovery-3mo

5

1169/820

3.19[1.19,8.56]

0.02

51.94

4

92%

<0.001

Potent recovery-12mo

7

1395/1574

2.37[1.30,4.33]

0.005

55.43

6

89%

<0.001

Readmission rate

7

11632/7060

0.83[0.74,0.94]

0.002

36.82

6

84%

<0.001

RARP=robot-assisted radical prostatectomy; RRP= retropubic radical prostatectomy; OR = odds ratio; WMD = weighted mean difference; CI = confidence interval; UTI=urinary tract infection; DVT=deep venous thrombosis.

Forest plot and meta-analysis of operating time between RARP and RRP.

Figure 2: Forest plot and meta-analysis of operating time between RARP and RRP. RARP = robot-assisted radical prostatectomy; RRP = retropubic radical prostatectomy.

Forest plot and meta-analysis of estimated blood loss between RARP and RRP.

Figure 3: Forest plot and meta-analysis of estimated blood loss between RARP and RRP. RARP = robot-assisted radical prostatectomy; RRP = retropubic radical prostatectomy.

Transfusion rate and postoperative recovery

Pooled data from the 26 studies [9, 10, 14, 21, 23, 24, 26, 29, 30, 34, 35, 40, 44-46, 54, 59, 64, 72, 73, 78, 80, 82, 84] reported transfusion rate between RARP and RRP, and the results showed that RARP was associated with lower transfusion rate (OR = 0.13; 95% CI: 0.08 to 0.21;P < 0.001) than RRP (Figure 4). Pooling data of 5 studies reported on the time to remove catheter, the forest plot showed that RARP had shorter time to remove catheter than RRP group (WMD = -3.04; 95% CI: -4.59 to -1.49; P < 0.001) (Figure S5). And pooling date of 11 studies [10, 23, 24, 34, 53, 54, 64, 75, 78] reported on length of hospital stay (LOS), the forest plot showed that RARP had a shorter LOS than RRP (WMD = -1.62; 95% CI: -2.42 to -0.82; P < 0.001) (Figure 5).

Forest plot and meta-analysis of transfusion rate between RARP and RRP.

Figure 4: Forest plot and meta-analysis of transfusion rate between RARP and RRP. RARP = robot-assisted radical prostatectomy; RRP = retropubic radical prostatectomy.

Forest plot and meta-analysis of the length of hospital stay between RARP and RRP.

Figure 5: Forest plot and meta-analysis of the length of hospital stay between RARP and RRP. RARP = robot-assisted radical prostatectomy; RRP = retropubic radical prostatectomy.

Outcomes of oncological variables

pathologic stage and pathologic Gleason score (Table 5)

14 studies [9, 20, 27-29, 32, 46, 48, 66, 70, 73, 76, 77, 80] on ≤pT2a, pT2b, ≥pT2c, 48 studies [8-13, 15, 16, 18, 19, 21, 26-29, 31, 32, 34, 42-44, 46-50, 52, 54, 55, 57, 58, 60, 61, 64-71, 73, 74, 76-78, 82, 85] on pathologic Gleason score (≤6; 7; ≥8) were reported, respectively. The results showed a statistical differences more Gleason score = 7 (OR: 1.17; 95% CI: 1.04 to 1.33; P = 0.01; Figure 6) performed RARP and more Gleason score ≥8 (OR: 0.68; 95% CI: 0.60 to 0.78; P < 0.001; Figure 6) in RRP. However, there were no statistical differences with respect to Gleason score≤6 (OR: 1.04; 95% CI: 0.91 to 1.18; P = 0.61; Figure 6) and pathologic T stage in the two groups (Figure S6,7,8)(Table 5).

Table 5: Overall analysis of pathologic and oncological outcomes comparing RARP with RRP

Outcome of interest

No. of studies

No.of patients

RARP/RRP

OR/WMD(95%CI)

p-value

Study heterogeneity

Chi2 df I2 p-value

Pathologic T stage

≤pT2a

13

2147/2174

1.11[0.93,1.31]

0.26

8.84

12

0%

0.72

pT2b

11

1959/2098

1.11[0.93,1.33]

0.25

13.91

10

28%

0.18

≥pT2c

14

2268/2485

0.93[0.76,1.13]

0.44

11.19

13

0%

0.60

Pathological Gleason score

≤6

48

15238/13412

1.04[0.91,1.18]

0.61

224.21

47

79%

<0.001

7

48

15238/13412

1.17[1.04,1.33]

0.01

230.23

47

80%

<0.001

≥8

48

15238/13412

0.68[0.60,0.78]

<0.001

101.358

47

54%

<0.001

PSM

49

20804/23133

0.88[0.78,1.00]

0.04

198.74

48

76%

<0.001

PSM for T2

28

10086/9711

0.77[0.63,0.95]

0.01

82.23

27

67%

<0.001

PSM for T3

18

2011/2125

1.46[1.27,1.67]

<0.001

18.66

17

9%

0.35

Mean lymph node yield

4

837/565

2.85[-0.92,6.63]

0.14

115.32

3

97%

<0.001

Positive lymph node

16

4162/6500

0.45[0.31,0.65]

<0.001

32.02

15

53%

0.006

BCR for free survival

10

4342/4176

1.33[1.01,1.76]

0.04

39.04

9

77%

<0.001

RARP=robot-assisted radical prostatectomy; RRP=retropubic radical prostatectomy; OR = odds ratio; WMD = weighted mean difference; CI = confidence interval; PSM=positive surgical margins; value of WMD.

Forest plot and meta-analysis of pathological Gleason Score between RARP and RRP.

Figure 6: Forest plot and meta-analysis of pathological Gleason Score between RARP and RRP. RARP = robot-assisted radical prostatectomy; RRP = retropubic radical prostatectomy.

Positive surgical margins and lymph node yield(Table 5)

49 studies [9-12, 14-16, 18, 19, 21, 26-29, 31-34, 36, 37, 39, 41-44, 46-49, 52, 54, 56-58, 61, 62, 65, 67-69, 73, 76-78, 80-82, 84] evaluating RARP and RRP reported positive surgical margins(PSM) rates. The results showed a significant difference with higher PSM rates in RRP group (OR:0.88; 95% CI: 0.78 to 1.00; P = 0.04)(Figure 7). PSM rates in pT3 cancers was higher in RARP group (OR:1.46; 95% CI: 1.27 to 1.67; P < 0.001) (Figure 8). However, the results showed that PSM rates in pT2 cancers was lower in RARP (OR:0.77; 95% CI: 0.63 to 0.95; P = 0.01)(Figure 9). Four studies [20, 43, 60, 73] comparing mean lymph node yield and the results showed that lymph node yield is higher in RARP (WMD: 1.61; 95% CI: 1.18 to 2.05; P < 0.001)(Figure S9), and 16 studies [20, 26, 33, 34, 39, 49, 58, 61, 64-68, 73, 84, 85] reported on positive lymph node, There was a statistical differences decreased positive lymph node in RARP than RRP (OR:0.45; 95% CI: 0.31 to 0.65; P < 0.001)(Figure 10).

Forest plot and meta-analysis of PSM between RARP and RRP.

Figure 7: Forest plot and meta-analysis of PSM between RARP and RRP. RARP = robot-assisted radical prostatectomy; RRP = retropubic radical prostatectomy.

Forest plot and meta-analysis of PSM for pT3 between RARP and RRP.

Figure 8: Forest plot and meta-analysis of PSM for pT3 between RARP and RRP. RARP = robot-assisted radical prostatectomy; RRP = retropubic radical prostatectomy.

Forest plot and meta-analysis of PSM for pT2 between RARP and RRP.

Figure 9: Forest plot and meta-analysis of PSM for pT2 between RARP and RRP. RARP = robot-assisted radical prostatectomy; RRP = retropubic radical prostatectomy.

Forest plot and meta-analysis of positive lymph node between RARP and RRP.

Figure 10: Forest plot and meta-analysis of positive lymph node between RARP and RRP. RARP = robot-assisted radical prostatectomy; RRP = retropubic radical prostatectomy.

Outcomes of complications(Table 4)

Pooling data from 25 studies [9, 11, 17, 23, 24, 26, 27, 29, 31, 34, 35, 40, 42, 46, 48, 52-54, 59, 64, 72, 73, 80, 82, 84] reported on overall complications, RARP had lower overall complications in the RARP than RRP(OR:0.43; 95% CI: 0.32 to 0.58; P < 0.001)(Figure 11). Next, a meticulous classification of overall complications showed that RRP had a higher incidence of rectal injury(OR:0.16; 95% CI: 0.07 to 0.39; P < 0.001)(Figure S10), pulmonary embolism(OR:0.47; 95% CI: 0.37 to 0.59; P < 0.001) (Figure S11), wound infections (OR:0.23; 95% CI: 0.11 to 0.46; P < 0.001) (Figure S12), bladder neck contracture(OR: 0.21; 95% CI: 0.08 to 0.60; P = 0.003) (Figure S13), urinary retention(OR:0.63; 95% CI: 0.47 to 0.84; P = 0.002)(Figure S14), deep venous thrombosis(OR:0.40; 95% CI: 0.25 to 0.66; P < 0.001) (Figure S15), urinary leakage(OR: 0.64; 95% CI: 0.58 to 0.70; P < 0.001) (Figure S16), lymphocele (OR:0.52; 95% CI: 0.29 to 0.94; P = 0.03) (Figure S17), and obturator nerve injury(OR:0.09; 95% CI: 0.01 to 0.75; P = 0.03) (Figure S18). There was no statistical differences between two groups in term of urinary tract infections(UTI)(OR:0.75; 95% CI: 0.37 to 1.54; P = 0.44)(Figure S19), ileus (OR:0.92; 95% CI: 0.56 to 1.51; P = 0.73) (Figure S20).

Urinary continence recovery and potent recovery(Table 4)

Pooling data of 9 studies [9, 21, 26, 50, 62, 70, 81, 83, 84] reported on 3-mo and 12-mo urinary continence recovery between two groups. The forest plot showed that there were no statistical differences on the 3-mo and 12-mo urinary continence between two groups (3mo: OR:1.54; 95% CI: 0.92 to 2.58; P = 0.10; 12mo: OR:1.03; 95% CI: 0.84 to 1.27; P = 0.75,respectively)(Figure 12, Figure S21). And the 3- and 12-mo potent recovery rate of RARP were better than RRP group, respectively (OR:3.19; 95% CI: 1.19 to 8.56; P = 0.02; OR: 2.37; 95% CI: 1.30 to 4.33; P = 0.005,respectively)(Figures 13,14).

Forest plot and meta-analysis of overall complications between RARP and RRP.

Figure 11: Forest plot and meta-analysis of overall complications between RARP and RRP. RARP = robot-assisted radical prostatectomy; RRP = retropubic radical prostatectomy.

Forest plot and meta-analysis of 3-mo urinary continence rate between RARP and RRP.

Figure 12: Forest plot and meta-analysis of 3-mo urinary continence rate between RARP and RRP. RARP = robot-assisted radical prostatectomy; RRP = retropubic radical prostatectomy.

Forest plot and meta-analysis of 3-mo potent recovery rate between RARP and RRP.

Figure 13: Forest plot and meta-analysis of 3-mo potent recovery rate between RARP and RRP. RARP = robot-assisted radical prostatectomy; RRP = retropubic radical prostatectomy.

Forest plot and meta-analysis of 12-mo potent recovery rate between RARP and RRP.

Figure 14: Forest plot and meta-analysis of 12-mo potent recovery rate between RARP and RRP. RARP = robot-assisted radical prostatectomy; RRP = retropubic radical prostatectomy.

Biochemical recurrence free survival and Readmission rate(Table 5)

Pooling data from 10 studies [12, 16, 34, 49, 56, 61, 65-67, 74] reported on biochemical recurrence(BCR) free survival, these results showed that RARP had a better BCR free survival than RRP(OR:1.33; 95% CI: 1.01 to 1.76; P = 0.04) (Figure 15). Pooling data from 7 studies [22, 35, 38, 53, 54, 59, 75] reported on readmission rate, the forest plot showed that RARP had a lower readmission rate than RRP(OR:0.83; 95% CI: 0.74 to 0.94; P = 0.002) (Figure 16).

Forest plot and meta-analysis of BCR free survival rate between RARP and RRP.

Figure 15: Forest plot and meta-analysis of BCR free survival rate between RARP and RRP. RARP = robot-assisted radical prostatectomy; RRP = retropubic radical prostatectomy.

Forest plot and meta-analysis of readmission rate between RARP and RRP.

Figure 16: Forest plot and meta-analysis of readmission rate between RARP and RRP. RARP = robot-assisted radical prostatectomy; RRP = retropubic radical prostatectomy.

Sensitivity analysis

42 qualified studies with patients’ baseline characteristic consistency(age, pre-PSA, BMI, prostate volume, P > 0.5) are analyzed by sensitivity analysis (Table 6). Compared with the original analysis, there was no change in the significance of any other outcomes except that readmission rate(P = 0.002 vs P = 0.13), and BCR for free survival(P = 0.04 vs. P = 0.55) were significantly different in sensitivity analysis. The method of sensitivity analysis can reduce the heterogeneity of studies to a certain extent.

Table 6: Sensitivity analysis of high quality studies comparing RARP with RRP

Outcome of interest

No. of studies

No.of patients

RARP/RRP

OR/WMD(95%CI)

p-value

Study heterogeneity

Chi2 df I2 p-value

Operation time, min

10

1523/1435

44.43[8.01,80.84]

0.02

1166.56

9

99%

<0.0001

Estimated blood loss, ml

8

1080/1102

-493.41[-672.09,-314.74]

<0.001

217.36

7

97%

<0.0001

Transfusion rate

18

16249/7209

0.16[0.09,0.28]

<0.001

116.44

17

85%

<0.0001

Remove the catheter, day

3

1173/735

-1.78[-2.50,-1.06]

<0.001

19.52

2

90%

<0.0001

Hospital stay, day

6

1568/1117

-0.75[-1.26,-0.24]

0.004

75.72

5

93%

<0.0001

Overall complications

14

2782/2767

0.50 [0.27, 0.92]

0.03

158.13

13

92%

<0.0001

Urinary continence-3mo

7

945/818

1.21[0.74,1.98]

0.45

13.33

6

55%

0.04

Urinary continence-12mo

4

942/1409

0.97[0.78,1.20]

0.79

10.89

6

45%

0.09

Potent recovery-3mo

4

722/685

4.50[1.91,10.62]

<0.001

17.64

3

83%

<0.001

Potent recovery-12mo

4

942/1409

1.58[1.05,2.36]

0.03

10.33

3

71%

0.02

Readmission rate

4

2850/3025

0.53[0.23,1.21]

0.13

24.10

3

88%

<0.001

Pathologic T stage

≤pT2a

10

1725/1871

1.02[0.83,1.26]

0.83

7.02

9

0%

0.63

pT2b

9

1675/1821

0.99[0.80,1.21]

0.90

8.07

8

1%

0.43

≥pT2c

12

1979/2212

0.98[0.79,1.21]

0.84

9.48

11

0%

0.58

Pathological Gleason score

≤6

27

5847/6576

0.99[0.87,1.13]

0.88

45.37

26

43%

0.01

7

27

5847/6576

1.14[1.02,1.28]

0.02

46.80

26

44%

0.007

≥8

27

5847/6576

0.79[0.67,0.92]

0.003

38.31

26

32%

0.06

PSM

39

13992/17806

0.87[0.76,0.99]

0.04

123.38

37

70%

<0.001

PSM for T2

16

6649/7986

0.71[0.53,0.95]

0.02

51.53

15

71%

<0.001

PSM for T3

12

1423/1713

1.39[1.19,1.63]

<0.001

9.38

11

0%

0.59

Mean lymph node yield

2

375/275

3.77[-5.87,13.41]

0.44

106.54

1

99%

<0.001

Positive lymph node

10

2668/3684

0.69[0.52,0.90]

0.006

9.31

9

3%

0.41

BCR for free survival

5

1192/1797

1.16[0.71,1.89]

0.55

23.76

4

83%

<0.001

RARP=robot-assisted radical prostatectomy; RRP=retropubic radical prostatectomy; OR = odds ratio; WMD = weighted mean difference; CI = confidence interval.

Discussion

The incidence of prostate cancer and its mortality is the first and the second common cancer in man, respectively [1]. Our results indicated that RARP seemed to have an younger age (WMD: -1.00; P < 0.001), and to have the lower level of pre-PSA (WMD: -0.93; P < 0.001) than RRP group, and that these differences are primarily due to surgeon’s preference for surgical modality. Another reason is that the younger is more easier to choose new approach. However, there is no difference on BMI and prostate volume between the two groups. Sensitivity analysis showed that there was no change in the significance of any other outcomes except that readmission rate(P = 0.002 vs P = 0.13) and BCR for free survival(P = 0.04 vs. P = 0.55).It demonstrated that selection bias of demographic and clinical data of patients is small between two groups.

Novara G et al [6] evaluated oncologic outcomes of RARP and RRP, and the results indicated that RARP had less EBL and transfusion rate than RRP. Their results presented similar results and strengthened our results. The other analyzed parameters operative time and complication rate were similar. However, in our meta-analysis, RARP had longer operative time than RRP(WMD:39.85min, P<0.001), which likely reflects the early learning curve with RARP. But the learning curve indicated that operative time was decreased with growing operative experience and it won’t influenced operative outcomes [88].

With regard to the pathologic outcomes, patients underwent RARP had more pathological Gleason score = 7, less pathological Gleason score ≥8, higher lymph node yield and fewer positive lymph node than RRP. However, the pathological T stage is no significant difference between the RARP and RRP group. LN yield was deemed an indicator of surgical quality by many surgeons [89]. RARP had a higher LN yield than RRP, the reason is that RARP has meticulous dissection with 3D vision and decrease the intraoperative blood loss which made the surgeon have more time and patience to acquiring higher LN yield. Therefore, the oncological outcomes in terms of PSM for T3 is higher in RARP than RRP. With the results that BCR free survival was higher in RARP than RRP. Some studies showed that the predictors of BCR were preoperative PSA. Gleason score, pathological stage, and PSM [49].

The experts suggested that patient outcomes and surgical approach were mainly required to improve for an accurate characterization of complications [90]. In our meta-analysis, Patients underwent RARP had fewer overall complications than RRP. The possible reason may be associated with lower EBL and less transfusion rate in RARP. Then a comprehensive classification of complications indicated that RRP had a higher incidence of rectal injury, pulmonary embolism, wound infections, bladder neck contracture, urinary retention, deep venous thrombosis, urinary leakage, lymphocele, and obturator nerve injury. There were no significant differences with regard to ileus and UTI between two groups.

Ficarra V et al [91] compared RARP with RRP with respect to 12-mo urinary continence. Their results indicated that RARP had a better 12-mo urinary continence recovery than RRP(OR:1.53; P = 0.03). However, our results indicated that there were no statistical differences with regard to 3-mo and 12-mo urinary continence in two groups. The urinary continence receiving RP is influenced by preoperative patient characteristics, surgical techniques, and so on. Some studies found that patient age [92, 93], BMI [94], comorbidity index [95], and prostate volume [96, 97] were also the potential predictors of urinary incontinence. Increasing age, higher BMI, and large prostate volume are correlated with high risk of urinary incontinence who underwent RP. However, the 3- and 12-mo potent recovery rate of RARP was also better than RRP group, respectively. Analysis of predictors indicated that peroperative parameters might influence potency results. Relevant predictors included age at surgery, baseline erectile function, and comorbidities [98]. Other authors also confirmed that age and baseline erectile function of patients were affected the potent recovery in nerve-sparing RARP [93, 99].

On the other hand, we found better BCR free survival and lower readmission rate in RARP group in the original analysis. The reason is that meticulous dissection, lower blood loss and complications might provide patients better oncologic prognosis in RARP group. However, we observed no statistical differences between RARP and RRP in sensitivity analysis. Therefore, multicenter, large sample, long follow-up RCTs are required to prove our findings.

Nevertheless, there were several limitations when analyzing and interpreting results in our meta-analysis. The major limitation is lack of well designed prospective, randomized control studies in our meta-analysis. Secondly, there existed heterogeneities of studies, especially in the comparing of the continuous data such as the length of hospital stay, operative time. whereas these parameters were influenced by the heterogeneities of patients’ conditions, surgeon’s surgical skills and the sample size of studies. In addition, short follow-up duration may have an influence on the confidence of outcomes. In the future, well-designed, prospective, multicenter randomized control studies are required to help us better demonstrate the advantages as well as drawbacks of this novel approach.

materials and Methods

Literature search strategy

To update previous systematic review [5-7, 91, 98, 100, 101], a systematic review of published literature was performed according to the Cochrane Handbook recommendations [102]. No ethic issues get involved in this article. A systematic dissertion was conducted using Medline, Embase, Pubmed, CNKI, and all relevant studies had been identified by the Cochrane Library. The following key words were used: “comparative studies”, “retropubic”, “open”, “radical prostatectomy “, “Da Vinci”, “robot-assisted”, and “prostate cancer”.

Data extraction and outcomes of interest

Two of the authors(JKH and TK) extracted data from the selected studies including: author identification, country, publication year, study design, age, No. of patients, operative approaches were mentioned previously, and results of intervention. All disagreements about eligibility were reached a consensus through authors discussion. Perioperative outcomes including operative time, EBL, LOS, overall complications, and oncological outcomes were compared between the two methods from all the studies that were finally selected. Overall complications were graded on the basis of the Clavien-Dindo system [103].

Inclusion criteria and exclusion criteria

Studies should satisfy the following requirements: (1) to compare RARP with RRP, (2) to display on outcome of two approaches, (3) to document the surgery as RARP or RRP, (4) to clearly document indications for prostatectomy with prostate cancer. Studies will be excluded if (1) the study was not satisfied inclusion criteria or (2) the outcomes of literature were not mentioned or the parameters were impossible to analysis for either RARP or RRP from the published findings and (3) studies focusing on pure robot surgery system and/or on single-site techniques.

Study quality assessment and level of evidence

In accordance with the criteria of Centre for Evidence-Based Medicine in Oxford, we evaluated the level of evidence(LOE) of included sixteen studies. The Jaded Score was applied to evaluated the methodological quality of RCTs [104]. The Newcastle-Ottawa Scale(NOS) was applied to assessed the methodological quality of non-RCTs observational studies [86, 105]. Two authors(JKH and TK) evaluated the quality of the studies and discrepancies were rechecked by the third reviewer(CZQ) and consensus was achieved by discussion.

Statistical analysis

All meta-analysis were conducted by Review Manger 5.3(Cochrane Collaboration, Oxford, UK). Continuous and dichotomous variables were calculated by weighted mean differences (WMDs) and odds ratios(ORs). All analysis results were reported with 95% confidence intervals(CIs). I2 test and chi-square-based Q test were applied to evaluated the quantity of heterogeneity, and when I2 > 50%, the evidence was considered to have substantial heterogeneity, the random- effects(RE) model would be applied, otherwise, the fixed effects(FE) model was applied. The presence of publication bias was evaluated by Egger’s test and funnel plot. Sensitivity analysis was used to estimate the influence of studies with a high risk of bias on the overall effect.

Conflicts of interest

The authors have no conflict of interest to disclose.

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