Comparison of transperitoneal and retroperitoneal laparoscopic nephrectomy for renal cell carcinoma: a systematic review and meta-analysis

Authors


Correspondence: Jian Huang, Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 W Yanjiang Road, Guangzhou 510120, China.

e-mail: yehjn@yahoo.com.cn

Abstract

What's known on the subject? and What does the study add?

  • Laparoscopic nephrectomy is now considered to be the reference procedure for kidney cancer. It can be performed via a transperitoneal or retroperitoneal approach. Each approach has its advantages and disadvantages. No definitive conclusions regarding objective difference between the two approaches have been reached to date.
  • This meta-analysis indicates that in appropriately selected patients, especially patients with posteriorly located renal tumors, the retroperitoneal approach may be faster and equally safe compared with the transperitoneal approach.

Objective

  • To evaluate the efficiency and safety of the retroperitoneal and transperitoneal approaches in laparoscopic radical/partial nephrectomy (RN/PN) for renal cell carcinoma.

Methods

  • A systematic search of PUBMED, EMBASE, and the Cochrane Library was performed to identify prospective randomized controlled trials and retrospective observational studies that compared the outcomes of the two approaches.
  • Outcomes of interest included perioperative and postoperative variables, surgical complications and oncological variables.

Results

  • Twelve studies assessing transperitoneal laparoscopic RN (TLRN) vs retroperitoneal laparoscopic RN (RLRN) and six studies assessing transperitoneal laparoscopic PN (TLPN) vs retroperitoneal laparoscopic PN (RLPN) were included.
  • The RLRN approach had a shorter time to renal artery control (weighted mean difference [WMD] 68.65 min; 95% confidence interval [CI] 40.80–96.50; P < 0.001) and a lower overall complication rate (odds ratio 2.12; 95% CI 1.30–3.47; P = 0.003) than TLRN. RLPN had a shorter operating time (WMD 48.85 min; 95% CI 29.33–68.37; P < 0.001) and a shorter length of hospital stay (WMD 1.01 days; 95% CI 0.39–1.63; P = 0.001) than TLPN.
  • There were no significant differences between the retroperitoneal and transperitoneal approaches in other outcomes of interest.

Conclusions

  • This meta-analysis indicates that, in appropriately selected patients, especially patients with posteriorly located renal tumours, the retroperitoneal approach may be faster and equally safe compared with the transperitoneal approach.
  • Despite our rigorous methodology, conclusions drawn from our pooled results should be interpreted with caution because of the inherent limitations of the included studies.
Abbreviations
RN

radical nephrectomy

PN

partial nephrectomy

TLRN

transperitoneal laparoscopic radical nephrectomy

RLRN

retroperitoneal laparoscopic radical nephrectomy

TLPN

transperitoneal laparoscopic partial nephrectomy

RLPN

retroperitoneal laparoscopic partial nephrectomy

WMD

weighted mean difference

RCT

randomized controlled trial

BMI

body mass index

EBL

estimated blood loss

WIT

warm ischaemia time

LOS

length of hospital stay

SCr

serum creatinine

OR

odds ratio

SMD

standardized mean difference

RE

random-effects model

FE

fixed-effects model

Introduction

Renal cell carcinoma represents 2–3% of all cancers, with the highest incidence occurring in Western countries [1]. The incidence rates of RCC have risen steadily during the last three decades in most of the world, with a mean increase of 2–3% per year [2]. Surgical removal of the kidney (radical nephrectomy [RN]) or the tumour (partial nephrectomy [PN]) is the only curative therapeutic approach for RCC [1]. Traditionally, nephrectomy has been performed using the open surgical approach through a large flank incision, which is associated with substantial pain and morbidity. In 1991, Clayman et al. [3] performed the first transperitoneal laparoscopic nephrectomy. Since then, laparoscopic nephrectomy has gained increasing worldwide acceptance because of its benefits in terms of patient recovery and perioperative morbidity [4, 5]. Long-term oncological studies have shown that the outcomes of laparoscopic nephrectomy are similar to those of open surgery [6-11].

Laparoscopic RN or PN can be performed via the transperitoneal or retroperitoneal approaches [12]. Each approach has its own advantages and limitations, and no definitive conclusions regarding objective differences in outcomes have been reached to date. We therefore performed a systematic review and meta-analysis of the available published literature to compare the outcomes of the two approaches.

Methods

Literature Search

A literature search of MEDLINE, EMBASE, and the Cochrane library was performed to identify relevant studies. No time or language restrictions were applied. The search terms were ‘(laparoscopic radical/partial nephrectomy) [Title/Abstract] AND (transperitoneal OR retroperitoneal) [Title/Abstract].’ Articles were also identified using the ‘related articles’ function. The reference lists of retrieved articles were manually searched to identify related articles. The latest date of this search was 29 April 2012.

Inclusion Criteria

The following inclusion criteria were used: (i) patients must have undergone preoperative staging including CT and/or MRI according to the 1997 TNM classification, and had a clinical stage of T1 to T3, (ii) clear documentation of the surgical technique as transperitoneal or retroperitoneal laparoscopic RN/PN, (iii) evaluation of at least one of the outcomes of interest mentioned below, and (iv) a randomized controlled trial (RCT) or retrospective comparative study design. When two studies were reported by the same institution and/or authors, the most recent report was used.

Exclusion Criteria

The following exclusion criteria were used: (i) the inclusion criteria were not met, (ii) paediatric patient population, (iii) obese patient population (body mass index [BMI] >40 kg/m2), or (iv) laparoscopic nephrectomy for benign lesions.

Data Extraction

Two reviewers (K.X. and T. L.) independently extracted data from the included studies, and disagreements were resolved by discussion until a consensus was reached. The following information was extracted from each study: first author; year of publication; study design; inclusion and exclusion criteria; matching criteria; number of patients in each group; characteristics of the study population; and outcomes of interest. In all cases of missing or incomplete data, the corresponding authors were contacted, but none provided any additional information.

Outcomes of Interest and Definitions

The following outcomes were used to compare transperitoneal and retroperitoneal laparoscopic RN/PN.

  1. Perioperative variables: operating time, estimated blood loss (EBL), time to renal vascular control in RN, and warm ischaemia time (WIT) in PN.
  2. Postoperative variables: length of hospital stay (LOS), time to first oral intake, analgesic requirements, and postoperative serum creatinine (SCr) level in PN.
  3. Surgical complications: overall complication rate, open conversion rate and blood transfusion rate. In studies reporting sufficient data, the overall complications were subdivided into: (i) intra-operative complications: abdominal visceral injuries (bowel, liver, spleen), renal vascular injuries, and other injuries (including pleural and lung injuries) and (ii) postoperative complications: bleeding, deep venous thrombosis, incisional hernia, wound infection, pulmonary atelectasis, and other.
  4. Oncological variables: overall recurrence rate, local recurrence rate, distant recurrence rate, overall survival rate, recurrence-free survival rate, and positive margin rate in PN.

Statistical Analysis

The present meta-analysis was performed according to the recommendations of the Cochrane Collaboration and the Quality of Reporting of Meta-analyses (QUORUM) guidelines [13, 14]. The weighted mean differences (WMDs) and the odds ratios (ORs) were used to compare continuous and dichotomous variables, respectively. If continuous variables were measured in different units, the standardized mean differences (SMDs) were used. All outcomes were reported with 95% CIs. For studies that presented continuous data as medians and ranges, means and SDs were calculated using the technique described by Hozo et al. [15]. Yates' correction was used for studies that contained a 0 in one cell of a number of events of interest in one of the two groups [16]. If there were no events of interest in either the transperitoneal laparoscopic RN (TLRN) or retroperitoneal laparoscopic RN (RLRN) groups, the study was discarded from the meta-analysis.

Statistical heterogeneity between studies was assessed using the chi-squared test with significance set at P < 0.10, and the quantity of heterogeneity was evaluated using the I2 statistic. The random-effects model (RE) was reported if there was heterogeneity between studies. Otherwise, the fixed-effects model (FE) was reported [17].

The methodological quality of RCTs was assessed using the Cochrane Risk of Bias Tool [18]. The methodological quality of observational studies was assessed using the Newcastle–Ottawa Scale, with some modifications to match the needs of the present study [19, 20]. The quality of studies was evaluated by examining three aspects of the study design: patient selection, comparability of the study groups, and assessment of outcomes. A score of 0 to 9 (allocated as stars) was allocated to each study. Studies achieving a score of ≥7 stars were considered to be of high quality.

Heterogeneity between studies in the RN group was assessed by two methods. First, sensitivity analysis was performed for RCTs and high-quality retrospective studies. Only outcomes of interest which were reported in >3 studies were included in the sensitivity analysis. Second, if an outcome was reported in >10 studies, meta-regression analysis was performed to find possible correlations between year of publication, study design, and outcome. Sensitivity and meta-regression analysis were not performed for the PN group owing to the limited number of studies. Publication bias was evaluated using funnel plots.

Statistical analysis was performed using Review Manager Version 5.0 (The Cochrane Collaboration, Oxford, London, UK) and the metareg procedure STATA 12.0 (StataCorp, College Station, TX). Generally, a P value < 0.05 was considered to indicate statistical significance (α = 0.05). For outcomes that underwent multiple comparisons, a correction factor was used to adjust the α level according to the Bonferroni method [21]. For example, operating time of the RN group was compared three times (overall analysis, sensitivity analysis of RCTs, and sensitivity analysis of high quality studies), so its significance level was adjusted to α = 0.05/3 = 0.0167.

Results

Description of Eligible Studies

Eighteen studies published from 2004 to 2011 fulfilled the inclusion criteria and were included in the meta-analysis (Fig. 1). Examination of the reference lists of these studies did not detect any further studies for evaluation. Twelve studies [22-33] assessed TLRN vs RLRN and six studies [34-39] assessed TLPN vs RLPN. The characteristics of included studies are shown in Table 1 [22-39]. Three studies [27, 28, 31] were RCTs, and the remaining studies were retrospective observational studies.

Figure 1.

Flow diagram of studies identified, included and excluded.

Table 1. Characteristics of included studies
First author, yearDesignNo. of patients: transperitoneal/retroperitonealBMI, kg/m2: transperitoneal/retroperitonealClinical stageComparability*Mean follow up, months: transperitoneal/retroperitonealStudy quality (score)
  1. *Comparability variables: 1 = age, 2 = gender, 3 = BMI, 4 = clinical stage, 5 = tumour side, 6 = tumour position, 7 = tumour size, 8 = previous abdominal surgery history, 9 = ASA score; †mean (range); mean (SD); §median (range); da Vinci robot-assisted laparoscopic PN.
  2. NA, data not available.
Laparoscopic RN
Berdjis, 2006 [33]Retrospective34/29NANA1,2, 5,8,923.9 (12–43)⋆⋆⋆⋆⋆⋆
Deger, 2007 [32]Retrospective125/38NANA125/26(3–75)⋆⋆⋆
Desai, 2005 [31]RCT50/5228.7 ± 6.7/28 ± 6.2NA1,2,3,4,5,815(3–24)/13.5(0.5–40)RCT
Ha, 2011 [30]Retrospective472/10824.2 ± 3.2/24.2 ± 3.0T1–T21,2,3,4,730 (2–93)/35.6 (4–110)⋆⋆⋆⋆⋆⋆
Jung, 2009 [29]Retrospective45/2123.4 ± 2.46/24.3 ± 2.17T1–T31,2,3,4, 5,7,943.6 (20–62)/19.1(14–33)⋆⋆⋆⋆⋆⋆⋆
Nadler, 2006 [28]RCT11/11

26.8 (22.0–34.8)/

27.8 (22.4–34.8)

T11,3,8,920RCT
Nambirajan,2004 [27]RCT20/20NAT1–T21,2,3,4, 5,6,7,8,917 (6–26)/15 (6–26)§RCT
Negoro, 2005 [26]Retrospective9/12

22.7 (17–25.7)/

24 (16.5–30.5)

T1–T32,3, 5,6,814.9⋆⋆⋆⋆⋆
Okegawa, 2008 [25]Retrospective47/5322.3 ± 2.8/23.1 ± 4.8T1–T21,2,3,4, 5,634.0(6–68)⋆⋆⋆⋆⋆⋆⋆
Taue, 2009 [24]Retrospective33/67NAT1a–T3a1,2, 5,6NA⋆⋆⋆⋆⋆
Tsujihata, 2008 [23]Retrospective34/33

23.6 (16.9–37.3)/

24.3 (18.0–30.5)

T1–T21,2,3,4, 5,6,727.8⋆⋆⋆⋆⋆⋆⋆
Xu, 2011 [22]Retrospective116/142NAT1–T21,2,3,4,5,6,724(6–35)⋆⋆⋆⋆⋆⋆⋆
Laparoscopic PN
Emara, 2011 [34]Retrospective6/27NAT1aNANA⋆⋆⋆⋆
Kieran 2007 [35]Retrospective45/27NAT1a1,2,4,6,7NA⋆⋆⋆⋆⋆⋆
Marszalek 2011 [36]Retrospective35/7027.9 ± 4.5/27.1 ± 4.1T1a1,2,3,4,5,6,7NA⋆⋆⋆⋆⋆⋆⋆
Ng CS 2005 [37]Retrospective100/6330.3 ± 8.6/29.4 ± 5.9T1a1,2,3,4,5,6,7,9NA⋆⋆⋆⋆⋆⋆⋆⋆
Tugcu 2011 [38]Retrospective26/23NAT1aNA11(2–35)/13(1–36)⋆⋆⋆⋆
Wright 2005 [39]Retrospective19/32NAT1a1,2,4,5,6,729/20⋆⋆⋆⋆⋆⋆

Methodological Quality of Included Studies

Agreement between the two reviewers for study selection was 96% and for quality assessment was 94%. For the three RCTs evaluated using the Cochrane Risk of Bias Tool, little information was provided on sequence generation or allocation concealment. One study [31] described sequence generation by computer, and in the other two studies the method was either not stated [27] or was poorly designed [28]. None of the three studies provided information regarding the blinding method. Follow-up time ranged from 12 to 20 months. Patients lost to follow-up or with benign histology of the nephrectomy specimen were excluded from analysis in one study [27] (Supporting Information Table S1).

For the retrospective observational studies, the risk of bias was evaluated using the modified Newcastle–Ottawa Scale. None of these studies adopted an appropriate protocol for treatment assignment, with allocation being at the physician's discretion in most studies. Seven studies [22, 23, 25, 29, 30, 36, 37] were comparable for age, gender, BMI, and clinical stage. Four studies assessing RN [22, 23, 25, 29] and two studies assessing PN [36, 37] scored ≥7 stars and were considered to be of high quality (Table S2).

Meta-Analysis of Perioperative Variables

Pooled data from the 12 studies that reported operating time for RN (Fig. 2A) showed that operating time was slightly shorter in RLRN than TLRN (RE: WMD 13.40 min; 95% CI 0.12–26.27; P = 0.05). This result was not significant after Bonferroni correction. Only two studies [26, 31] reported time to renal vascular control. Time to renal artery control was significantly longer in TLRN than RLRN (RE: WMD 68.65; 95% CI 40.80–96.50; P < 0.001) and time to renal vein control was also significantly longer in TLRN than RLRN (RE: WMD 53.52; 95% CI 40.41–66.63; P < 0.001). Pooled data from the 10 studies [22-31] that reported EBL for RN showed no significant difference between RLRN and TLRN (FE: WMD −9.43 mL; 95% CI −23.77–4.91; P = 0.20).

Figure 2.

Meta-analysis of operating time: A, TLRN vs RLRN and B, TLPN vs RLPN.

Pooled data from the five studies [35-39] that reported operating time for PN showed that operating time was significantly shorter in RLPN than TLPN (RE: WMD 48.85 min; 95% CI 29.33–68.37; P < 0.001 [Fig. 2B]). Pooled data from the six studies [34-39] that reported WIT for PN showed no significant difference between TLPN and RLPN (FE: WMD 1.23 min; 95% CI −0.36–2.82; P = 0.13). Pooled data from the four studies [35, 37-39] that reported EBL for PN showed no significant difference between TLPN and RLPN (FE: WMD 72.38 mL; 95% CI −3.92–148.68; P = 0.06).

Meta-Analysis of Postoperative Variables

There were no significant differences between TLRN and RLRN in LOS (RE: WMD 0.30 days; 95% CI −0.41–1.02; P = 0.40) or time to first oral intake (RE: WMD 0.27 days; 95% CI −0.10–0.64; P = 0.15). Five studies reported analgesic requirements in detail, but different analgesics were used in different studies. Three studies used morphine [27, 28, 31], one used pethidine [29], and one used non-steroidal anti-inflammatory drugs [23]. No significant difference in analgesic requirements was found between TLRN and RLRN (FE: SMD 0.03; 95%CI −0.20–0.26; P = 0.82 [Table 2]).

Table 2. Overall analysis of transperitoneal vs retroperitoneal laparoscopic RN/PN
Outcome of interestNo. of studiesNo. of patients, transperitoneal/retroperitonealWMD/SMD*/OR (95% CI)PStudy heterogeneity
Chi-squared testdfI2P
  1. *Values of SMD; Not significant after Bonferroni correction; Values of OR. §Significant after Bonferroni correction.
Analysis of laparoscopic RN
Perioperative variables
Operating time, min12996/58613.40 (0.12, 26.67)0.0534.931169%<0.001
Time to renal artery control, min259/6468.65 (40.80, 96.50)<0.0014.05175%0.04
Time to renal vein control, min259/6453.52 (40.41, 66.63)<0.001010%0.98
EBL, mL10837/519−9.43 (−23.77, 4.91)0.2016.98947%0.05
Postoperative variables
LOS, days9365/4110.30 (−0.41, 1.02)0.4051.62885%<0.001
Time to first oral intake, days8345/3890.27 (−0.10, 0.64)0.15117.33794%<0.001
Analgesic requirement6207/1900.12 (−0.08, 0.32)*0.252.9150%0.71
Surgical complications
Overall complications10515/4762.12 (1.30, 3.47)0.003§6.5490%0.68
Intraoperative complications9504/4552.17 (1.08, 4.35)0.033.9080%0.87
Postoperative complications8461/4131.69 (0.91, 3.14)0.105.0570%0.65
Open conversion6366/3442.69 (0.96, 7.49)0.062.9850%0.70
Blood transfusion4134/1691.34 (0.45, 3.98)0.592.7530%0.43
Oncological variables
Total recurrence8884/4461.46 (0.74, 2.88)0.273.5470%0.83
Local recurrence2517/1290.98 (0.24, 4.03)0.980.5410%0.46
Distant recurrence8884/4461.31 (0.66, 2.60)0.443.0070%0.89
Analysis of laparoscopic PN
Perioperative variables
Operating time, min5225/21548.85 (29.33, 68.37)<0.00118.27478%0.001
WIT, min6231/2421.23 (−0.36, 2.82)0.138.96544%0.11
EBL, mL4190/14572.38 (−3.92, 148.68)0.067.51360%0.06
Postoperative variables
LOS, days5225/2151.01 (0.39, 1.63)0.00125.91485%<0.001
Postoperative SCr, mg/dL2145/900.02 (−0.08, 0.11)0.691.16114%0.28
Surgical complications
Overall complications5205/2191.59 (0.94, 2.71)0.095.54428%0.24
Intraoperative complications4170/1492.30 (0.83, 6.40)0.113.58316%0.31
Postoperative complications4199/1921.33 (0.73, 2.41)0.353.0933%0.38
Conversion rate5205/2192.14 (0.85, 5.39)0.112.9340%0.57
Oncological variable
Positive margin rate4199/1921.29 (0.48, 3.46)0.611.2230%0.75

Pooled data from the five studies [35-39] that reported LOS for PN showed a significant difference favouring RLRN (RE: WMD 1.01 days; 95% CI 0.39–1.63; P = 0.001). Only one study [37] reported postoperative morphine equivalent requirements, and found no significant difference between TLPN and RLRN (38.5 ± 35 mg vs 27.6 ± 31 mg; P = 0.10). Pooled data from the two studies [35, 37] that reported postoperative SCr level for PN showed no significant difference between TLPN and RLRN (FE: WMD 0.02 mg/dL; 95% CI −0.08–0.11; P = 0.68).

Meta-Analysis of Surgical Complications

The overall complication rate was significantly lower in RLRN than TLRN (FE: OR 2.12; 95% CI 1.30–3.47; P = 0.003 [Fig. 3A]). This result remained significant after Bonferroni correction. The intra-operative complication rate was also significantly lower in RLRN than in TLRN (FE: OR 2.17; 95% CI 1.08–4.35; P = 0.03). There were no significant differences between RLRN and TLRN in postoperative complication rate (FE: OR 1.69; 95% CI 0.91–3.14; P = 0.03), open conversion rate or blood transfusion rate (Table 2).

Figure 3.

Meta-analysis of overall complications: A, TLRN vs RLRN and B, TLPN vs RLPN.

There were no significant differences between TLPN and RLPN in overall complication rate (Fig. 3B), intra-operative complication rate, postoperative complication rate, or open conversion rate (Table 2).

Meta-Analysis of Oncological Variables

There were no significant differences between TLRN and RLRN in overall recurrence rate, local recurrence rate, or distant recurrence rate (Table 2). Only two studies [25, 30] reported 5-year overall and recurrence-free survival rates, and these outcomes were not suitable for meta-analysis. These studies did not show a significant difference between TLRN and RLRN.

Pooled data from the four studies [35-37, 39] that reported positive surgical margin rates for PN showed no significant difference between TLPN and RLPN (FE: OR 1.29; 95% CI 0.48–3.46; P = 0.03). None of the six studies assessing PN reported recurrence or survival rates, making it impossible to perform meta-analysis on these outcomes.

Sensitivity Analysis and Meta-Regression

The sensitivity analysis for RN (Table 3) included three RCTs and four retrospective studies which scored ≥7 stars on the modified Newcastle–Ottawa Scale. The pattern of differences was similar to that of the original analysis, except that the RCTs did not show a significant difference in operating time between RLRN and TLRN. Heterogeneity between studies was not significantly reduced by the sensitivity analysis.

Table 3. Sensitivity analysis comparison of transperitoneal and retroperitoneal laparoscopic RN
Outcome of InterestNo. of studiesNo. of patients, transperitoneal/retroperitoneal RNWMD/SMD*/OR (95% CI)PStudy heterogeneity
Chi-squared testdfI2P
  1. *Values of SMD; Values of OR; Not significant after Bonferroni correction.
Analysis of RCTs
Operating time, min381/8312.89 (−35.93, 61.71)0.6018.52289%0.001
EBL, mL381/83−23.77 (−54.38, 6.85)0.131.6720%0.43
LOS, days381/83−0.59 (−1.64, 0.45)0.274.67257%0.10
Analgesic requirement381/83−0.00 (−0.31, 0.30)*0.980.4820%0.79
Overall complications381/831.75 (0.77, 3.98)0.180.1720%0.92
High-quality observational studies (≥7 stars) and RCTs
Operating time, min7323/33213.13 (−5.81, 32.06)0.1720.95671%0.002
EBL, mL7323/3320.65 (−27.45, 28.75)0.9613.09654%0.04
LOS, days7323/3320.14 (−0.59, 0.86)0.7125.07676%<0.001
Time to first oral intake, days6303/3100.35 (−0.12, 0.81)0.14105.55595%<0.001
Analgesic requirement5160/1370.03 (−0.20, 0.26)*0.820.5740%0.97
Overall complications7323/3321.86 (1.04, 3.30)0.042.0560%0.91
Open conversion4208/2392.47 (0.68, 8.96)0.170.1830%0.98

Only two studies [36, 37] assessing PN scored ≥7 stars on the modified Newcastle–Ottawa Scale, so it was not appropriate to perform sensitivity analysis on this group.

Ten or more studies assessing RN included analysis of operating time, EBL and overall complication rate. Meta-regression analysis showed no significant correlations between year of publication, type of study design, and the above three outcomes.

Publication Bias

The funnel plot for operating time is shown in Fig. 4A. Four studies reported asymmetrical 95% CIs, indicating potential publication bias. The funnel plot for overall complication rate is shown in Fig. 4B. All study outcomes were within the 95% CIs and were distributed symmetrically, showing no evidence of publication bias.

Figure 4.

Funnel plots of A, operating time and B, overall complications in studies of laparoscopic radical nephrectomy.

Discussion

This meta-analysis included 12 studies comparing RLRN with TLRN and six studies comparing RLPN with TLPN. The results showed that RLRN had a shorter time to renal vascular control and a lower overall complication rate than TLRN, and that RLPN had a shorter operating time and a shorter LOS than TLPN. We found no significant differences between the groups in other outcomes.

According to our initial analysis, RLRN had a shorter operating time than TLRN, but the 13.4 min difference in operating time was probably not clinically significant. According to the data of two studies [26, 31], the mean time to renal artery and renal vein control was significantly shorter, by 68.65 min and 53.52 min, respectively, in RLRN than TLRN. These results were to be expected, as the transperitoneal approach requires considerable mobilization to access the renal hilum, whereas the retroperitoneal approach provides direct and rapid access to the renal hilum. There were no significant differences between RLRN with TLRN in EBL, LOS, time to first oral intake, and analgesic requirement.

The overall and intraoperative complication rates were significantly lower in RLRN than in TLRN, but there was no significant difference in postoperative complication rate between these two groups. Unfortunately, most of the studies reported overall complication rate without reporting the specific events, which may have introduced bias. According to the limited data available, visceral organ damage and renal vascular injuries accounted for most of the intra-operative complications in TLRN. These findings cannot support a claim that RLRN is safer than TLRN, as allocation to treatment groups was at the discretion of the attending physician in most studies, with TRLN used more often in complicated cases. This might have been a source of bias, but our analysis indicates that RLRN is at least as safe as TRLN.

There were no significant differences in total recurrence rate, local recurrence rate, or distant recurrence rate between RLRN and TLRN. The length of follow-up varied among studies, which could be a potential source of bias. Liver, lung and brain metastasis were the most common types of distant recurrence, and the most reported postoperative pathology stages were pT2 or pT3. Only two studies [25, 30] reported 5-year overall and recurrence-free survival rates, and these studies did not report hazard ratios, which made it impossible to compare long-term survival rates between these two approaches. Long-term follow-up of the patient groups in these studies would be useful.

Analysis of the RCTs assessing RN did not show any differences between groups in any of the outcomes studied except for operating time and overall complication rate, and these differences were not statistically significant. Although a meta-analysis of RCTs only would be ideal, there were too few RCTs to enable us to draw any definitive conclusions. We performed a further sensitivity analysis including the RCTs and the high-quality retrospective studies. The results remained similar to those of the overall analysis, except that the difference in operating time between groups became nonsignificant.

Most of the studies included in the meta-analysis of RN evaluated patients with T1/2 tumours only. The retroperitoneal approach may not have a large role to play in the treatment of T2–4, N+ lesions. With the emergence of nephron-sparing surgery as the standard of care for T1 and many T2 renal tumours, laparoscopic RN is primarily reserved for tumours of grade T2 or higher [1]; however, there is an increasing interest in revisiting the retroperitoneal approach for PN with robotic assistance [40]. We performed a meta-analysis of transperitoneal vs retroperitoneal laparoscopic and robot-assisted PN as a separate section of our study.

Disadvantages of the retroperitoneal approach include a small working space, limited landmarks, and the risk of becoming disoriented [39]; however, our analysis showed that RLPN had a significantly shorter operating time than TLPN. In the included studies, the retroperitoneal approach was selected primarily for posteriorly located tumours. By avoiding bowel mobilization, RLPN seems to provide more direct access to the kidney and the renal hilum, thus decreasing operating time. The LOS was also significantly shorter in RLPN than TLPN. We found no significant differences in EBL, WIT, postoperative SCr level, complication rate, conversion rate, or positive surgical margin rate between RLPN and TLPN. We concluded that the retroperitoneal approach is faster and equally safe compared with the transperitoneal approach in appropriately selected patients. Long-term follow-up in future studies is needed to evaluate the oncological outcomes of the two approaches.

The present meta-analysis has the following limitations that must be taken into account. First, except for three small scale RCTs, all the studies included were observational. Studies were conducted with varying protocols and different levels of surgical expertise. Adequate random sequence generation was performed in only one study [31], and the absence of allocation concealment and blinding may have influenced the measurement of postoperative variables. Second, the studies included in the analysis were mostly conducted at major institutions, and therefore the patients evaluated might not reflect patient populations in the community. Computer-based literature searching is essential. It is, however, possible that not all the relevant studies were identified because ‘grey literature’ was not included in this study. Third, heterogeneity between studies was low for most of the dichotomous variables examined in this analysis, but was marked for all the continuous variables. There was significant variability in terms of definitions, inclusion criteria, exclusion criteria, operating technique, and measurement of outcomes. It was not possible to match all patient groups for age, BMI, tumour stage and previous abdominal history. All these factors may have contributed to the high heterogeneity between studies. Use of the RE model for pooled data might minimize the effects of heterogeneity, but does not abolish them. The degree of heterogeneity fell for most outcomes with sensitivity analysis, but this difference was not significant. Fourth, some data were reported as median (range), which may be because these variables were not normally distributed. We calculated the mean (SD) values from data ranges, or P values, therefore, the bias of the pooled effect should be considered. Finally, some authors did not report the proportion of patients lost to follow-up, which may influence the reliability of the conclusions.

To our knowledge, this is the first meta-analysis comparing transperitoneal and retroperitoneal laparoscopic RN/PN for RCC. This study was conducted at an appropriate time because enough data have accumulated for inspection by meta-analytical methods. We applied multiple strategies to identify studies, strict criteria to include and evaluate the quality of the studies, and sensitivity analysis to minimize the effects of heterogeneity. Non-English language studies [26, 29] were included to minimize publication bias. This analysis therefore provides the most up-to-date information in this area.

In conclusion, the present meta-analysis suggests that RLRN has a shorter time to renal vascular control than TLRN, and RLPN has a shorter operating time than TLPN. In appropriately selected patients, especially patients with posteriorly located renal tumours, the retroperitoneal approach may be faster and equally safe compared with the transperitoneal approach. Despite our rigorous methodology, the inherent limitations of the included studies should be considered, and conclusions drawn from our pooled results should be interpreted with caution.

Contributors

Xinxiang Fan and Kewei Xu: literature search and review, data extraction and analysis, and writing of the manuscript. Kewei Xu and TianXin Lin: literature review, data extraction and analysis. Hao Liu, Zi Yin, Wen Dong and Hai Huang: data analysis and interpretation. Jian Huang: data analysis and interpretation, and provided scientific advice.

Acknowledgements

This study was supported by The National Natural Science Foundation of China (Grant No. 81001138, 81071688, 81172431, 81272808), and Guangdong Province Natural Scientific Foundation (Grant No. 07117336, 10151008901000024).

Conflicts of Interest

The authors declare no conflicts of interest.

Ancillary