Comparison of efficacy and safety of conventional laparoscopic radical prostatectomy by the transperitoneal versus extraperitoneal procedure

Worldwide, prostate cancer (PCa) is the second most common malignancy in males. We undertook a meta-analysis to compare the efficacy and safety of conventional laparoscopic radical prostatectomy with a transperitoneal (TLRP) approach, versus that of an extraperitoneal (ELRP) approach, for treatment of localized PCa. A comprehensive literature search retrieved 14 publications, with a total of 1715 patients. Meta-analysis of these studies showed that an ELRP approach was associated with a significantly shorter postoperative catheterization time (MD: 1.99; 95% CI: 0.52 to 3.54; P = 0.008), less blood transfusion rate (OR: 2.05; 95% CI: 1.03 to 4.06; P = 0.04), shorter intestinal function recovery time (MD: 0.08; 95% CI: 0.52 to 1.09; P < 0.0001) and shorter hospitalization days (MD: 2.71; 95% CI: 1.03 to 4.39; P = 0.002). In addition, our results showed no statistically significant differences between the two groups in operation time (MD: 19.39; 95% CI: −6.67 to 45.44; P = 0.014), intraoperative blood loss (MD: 4.89; 95% CI: −105.00 to 114.79; P = 0.93) and total complication rate (RR: 1.22; 95% CI: 0.86 to 1.74; P = 0.27). In summary, our meta-analysis showed that ELRP is likely to be a safe and feasible alternative for localized PCa patients compared with TLRP.


Results
We formulated a comprehensive search strategy to identify all relevant studies, regardless of the language or publication status. Through literature selection, 14 studies were identified from the literature search. The literature screening process is summarized in Fig. 1.
A total of 1715 patients were included in the 14 studies 7-20 ; of these, 939 underwent TLRP and 776 underwent ELRP. All included studies reported on the number of patients. Two studies failed to report mean PSA levels 12,14 . Seven studies reported on the mean Gleason scores 7,[9][10][11]16,18,19 . The basic characteristics and quality assessments of the included studies were summarized in Table 1.
No heterogeneity was exist in the pooled analysis (P = 0.81; I 2 = 0%), a fixed-effect model was used for statistical analysis. ELRP group was associated with a lower total complication rate than TLRP group, but the meta-analysis demonstrated that no statistically significant difference was exist (RR: 1.22; 95% CI: 0.86 to 1.74; P = 0.27) (Fig. 8).

Discussion
Radical prostatectomy is one of the ways for treat patients with localized PCa 3 . The advantages of LRP over open radical prostatectomy include a reduced intraoperative blood loss, a lower blood transfusion rate, shorter hospitalization days, a shorter time to resumption of routine activity and improved scar heals well 21,22 . However, robot-assisted radical prostatectomy has higher costs than conventional LRP   technology 23 . In current practice, conventional LRP approach for localized PCa patients is available [14][15][16][17][18][19][20][21] .
In addition, either a transperitoneal or an extraperitoneal approach has been demonstrated to be both safe and effective. Although there is a meta-analysis reporting on the safety and efficacy between TLRP and ELRP that was published in Chinese 24 , this is necessary to update this meta-analysis for provided update evidence regarding their benefits for patients with localized PCa. Therefore, we conduct the systematic review and meta-analysis to compare the safety and efficacy of TLRP with ELRP for the treatment of localized PCa. The results of the present meta-analysis demonstrated a similar operation time with TLRP, relative to ELRP. Studies conducted by Erdogru et al. 10 and Wang et al. 16 reported that TLRP was associated with a shorter operation time, compared with ELRP. Conversely, other research showed ELRP had a shorter operation time, compared with TLRP 9,13-15 . To our surprise, after excluding study data from Siqueira et al. 17 from our meta-analysis, a statistically significant difference was found between the TLRP and ELRP groups. Furthermore, our finding from the pooled analysis revealed that operating times were 30.75 minutes shorter in the ELRP group, compared with the TLRP group; and this difference was statistically significant. The findings from the pooled analysis were consistent with those of 2 studies that were not included in our meta-analysis 21,22 . It is plausible that the shorter operative time might result from the direct access to the retropubic space and avoidance of bowel handling in ELRP. We supposed that it is possible that this result was influenced by the small sample sizes or a lack of surgical experience in the ELRP procedure in the study. Therefore, it is necessary to evaluate the operation time of TLRP versus ELRP in further, high quality, randomized controlled trials with larger sample sizes.
Our findings reveal that the average blood loss during TLRP group was similar to that associated with ELRP group, and the observed difference did not achieve statistical significance. Therefore, ELRP had no advantages, in terms of reduced blood loss, compared with TLRP. However, our results regarding blood transfusion rate clearly indicated that the TLRP group had a rate 2.05 times higher than the ELRP group. This present findings also agree with the results of previous controlled clinical trial 15,16 .
The present results indicate a significantly faster intestinal function recovery time following ELRP, compared with TLRP. From Fig. 4, it is clear that the mean intestinal function recovery time in the ELRP group was 0.8 times faster than seen in TLRP group. Porpiglia et al. reviewed 160 patients who underwent radical prostatectomy, either TLRP or ELRP; they also reported a faster intestinal function recovery time in the ELRP group 13 . Our findings are also consistent with the findings of a previous study by Liu et al. 24 .
Additionally, the present meta-analysis demonstrated that ELRP was superior to TLRP with regard to postoperative catheterization time and hospitalization days. However, there was no statistically significant difference in terms of overall complication rate. As described previously 23,24 , our results are in

Figure 8. Forest plot of total complication rate between TLRP and ELRP group.
Scientific RepoRts | 5:14442 | DOi: 10.1038/srep14442 agreement with those of researchers, suggesting a shorter catheterization time and hospitalization days in the ELRP group. There was a similar overall rate of complications in the 2 groups [11][12][13][14][15][16][17][18][19][20] . Total complication rates generally include bleeding, intra-abdominal organ and vessel injuries, urinary leakage, ileus, anastomotic leakage, pulmonitis, lymphocele formation, and stricture at vesicourethral anastomosis. Certainly, we also thought that the rate of complications may be associated with surgical experience and skill. Complication rates were reported by research centers, and revealed a mean complication rate of approximately 10% for the each approach 25,26 . Results of the current study showed a total complication rate of 11.4% (86/753) in the TLRP group, and 9.8% (61/623) in the ELRP group; the difference was not statistically significant, consistent with the findings of the above wor 25,26 .
Overall, it is generally considered that the main advantages of the TLRP procedure are; (1) the faster placement of trocars; and (2) the larger cavity, which allows placement of the specimen bag out of the operative field, improving vision and facilitating the vesicourethral anastomosis. However, TLRP also has many disadvantages, including the requirement of a much steeper Trendelenburg position to move the bowel out of the pelvic cavity. This position might cause upper airway and facial swelling, which may postpone extubation, lengthen the recovery time, and increase the risk of brachial plexus injury 27 . The bowels may adhere in the retropubic space of Retzius after the operation, and radiation therapy can lead to radiation enteritis. Such factors might explain the longer catheterization time and longer duration of hospitalization days associated with TLRP.
The ELRP approach has several advantages; the procedure can be finished extraperitoneally and the Trendelenburg required is less steep, compared with the transperitoneal route. The incidence rate of bowel lesions, ileus, and peritonitis is therefore lower, and the procedure prevents herniation from the trocar ports. The peritoneum can isolate the operative field from the abdominal cavity, bleeding does not contact the bowel and reflex ileus is avoided; even a poor anastomosis could not result in urinary ascites with its associated complications 8,9 . In addition, a self-made gasbag is inserted sufflating gas to build a pneumopreperitoneum. This keeps pressure on the peripheral tissues, and inhibits serious bleeding. However, there is also a greater risk of rectal injury with the initial dissection of the seminal vesicles, especially in obese patients. Therefore, from the above-mentioned technical considerations, ELRP might have lower blood transfusion rate and shorter intestinal function recovery time, but a similar total complication rate.
Our meta-analysis detected heterogeneity in the operation time, intraoperative blood loss, postoperative catheterization time, postoperative intestinal function recovery time, and hospitalization days. We maintain that these heterogeneities might have resulted from differences in the skill of the surgeon. Additionally, the small sample sizes, and difference between patients, which included different clinical stages and prostate volume, could have potentially increased the degree of heterogeneity. Additional factors that have been predicted to potentially amplify heterogeneity between studies include differences in country, follow-up periods, and a lack of uniformity in surgical procedure measurement standards.
Our systematic review and meta-analysis has several limitations. The study quality estimation was influenced by the non-randomized studies, and there was inadequate information provided in terms of methodological differences among the included studies. Some studies did not adequately report the outcomes measures. In addition, we could not obtain some relevant data, which may have introduced bias. Nonetheless, with the exception of operation time, the all conclusions were stable and were not impacted by the sensitivity analysis, in which each study was sequentially excluded from the pooled analysis.
In summary, both ELRP and TLRP have advantages and disadvantages; the efficacy and safety of LRP related to standardization of the procedure and the personal experience of the surgeon. However, this present meta-analysis has demonstrated that ELRP is associated with a lower blood transfusion rate, shorter catheterization time, faster intestinal function recovery time, and shorter hospitalization days, compared with TLRP. In addition, the approaches are similar in terms of operation time, intraoperative blood loss, and total complication rate. Therefore, the present meta-analysis showed that ELRP is likely to be a safe and feasible alternative for patients with localized PCa.

Methods
Search strategy. We performed a systematic literature search up to May 1, 2014 using Medline, Embase, the Cochrane library, and Google Scholar databases. We did not restrict our search to articles published in English. The following search terms were used: transperitoneal; extraperitoneal; LRP; PCa; or prostatic neoplasms. We also searched the relevant references of all included studies, and manually searched urology, andrology, and oncology diseases journals for further relevant articles. The search strategy was independently performed by 2 reviewers. Study selection. All randomized or non-randomized controlled trials that compared TLRP with ELRP and included data on at least 1 of the pre-defined outcome measures were eligible for inclusion. Studies were excluded if they met any of the following criteria; (1) not comparative studies for TLRP versus ELRP; (2) robot-assisted radical prostatectomy; (3) study sample did not comprise PCa patients. When multiple publications from the same study or institution were available, we used the publication with the largest number of cases. Review of all titles and abstracts of the included studies was independently performed by 2 authors, and full texts were screened when necessary. Any disagreements were resolved in consultation with Wei Q. All of the authors have reached a consensus with respect to included/excluded studies.
Data extraction. The following information was recorded independently by 2 reviewers, using data extraction forms: the first author's name, year of publication, origin country, total number of patients, average age, prostatic specific antigen level, Gleason score and the type of research design. All extracted data was cross-checked, and discrepancies in the data were resolved after discussions among all authors. The following outcome measures were recorded from the included studies: (1) operation time; (2) intraoperative blood loss; (3) blood transfusion rate; (4) postoperative catheterization time; (5) intestinal function recovery time; (6) hospitalization days; (7) total complication rate. All of the authors have reached a consensus with respect to the extracted data.
Quality assessment. The quality of the included studies was measured independently by two reviewers using a modification of the Newcastle-Ottawa Scale 28 . Review scores ranged from 0 to 9 points for each trial. Scores ranging from 0 to 4 were defined as low-quality while those ranging from 5 to 9 were defined as high-quality. Any disagreements were resolved after discussion between the two reviewers. All of the authors have reached a consensus with respect to the quality of the included studies.
Statistical analysis. All statistical analyses were conducted using Review Manager, version 5.1.0 (Cochrane Collaboration, Oxford, UK). Statistical analysis of dichotomous variables (blood transfusion rate and total complication rate) was performed using the OR as the summary analysis, while continuous variables (operation time, intraoperative blood loss, postoperative catheterization time, intestinal function recovery time and hospitalization days) were analyzed using the MD; accompanying 95% CI and P-value were reported. For all statistical results, P < 0.05 was considered statistically significant. The Mantel-Haenszel chi-squared test for heterogeneity was conducted. Heterogeneity was assessed using the I 2 statistic. I 2 values of < 50% were defined as acceptable; a fixed-effects models was used, otherwise random-effects model was applied for the meta-analysis.