Benign prostatic hyperplasia (BPH) is a common disease in elderly men, and its incidence increases gradually with age. The obstruction of the lower urinary tract caused by an enlarged prostate brings great trouble to the life of patients (1). Surgical intervention is required when patients with BPH have severe complications or non-responding well to pharmacological treatment (2). Current guidelines recommend open simple prostatectomy (OSP) as the gold standard procedure for large BPH (prostate volume > 80 mL) (3, 4), but it is related to higher postoperative complications and longer length of stay (LOS) (5, 6). For these reasons, several surgical approaches including endoscopic enucleation of the prostate (EEP) and minimally invasive simple prostatectomy (MISP) have been mentioned and introduced to reduce the morbidity associated with open surgery.

EEP based on laser or bipolar technology has proven to be a safe and efficacious treatment for BPH. A growing body of literature suggests that it has superior perioperative outcomes while providing the same clinical efficacy as OSP (7). Therefore, EEP is considered the standard therapy for treating large prostates (3). In recent years, laparoscopic and robotic techniques have been widely adopted in urological surgery because of their advantages of low trauma and quick recovery. MISP is a relatively new technique for large BPH through a laparoscopic or robot-assisted approach. This technique appears to be more attractive than OSP, as it offers less blood loss, shorter LOS, and lower perioperative complications (8). Both MISP and EEP are considered alternatives to OSP (7, 8), however, there is no common consensus as to which approach is most appropriate.

Therefore, this study aimed to incorporate available clinical studies to systematically compare the efficacy and safety of MISP and EEP for large BPH, and provide the latest evidence for clinical practice.

This present study has been reported following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement (9) and has been registered on PROSPERO: CRD42021239950.

Over the past several decades, OSP has been the surgical method of choice for treating large BPH, and it may disappear as minimally invasive methods continue to advance (18). EEP and MISP are currently the preferred alternative procedures, but the superiority of these two approaches remains controversial. A previous meta-analysis of comparatives studies by Abi (20) aimed at comparing MISP with laser enucleation revealed that the two methods had similar postoperative IPSS (p = 0.23) and major complications (p = 0.41). They also concluded that laser enucleation had a shorter operative time (p = 0.006), LOS (p < 0.001) and catheterization time (p < 0.001) than MISP. One problem with the Abi study is that although five studies were included for analysis, only two or three were available for comparison of postoperative functional outcomes. Therefore, with the publication of new studies related to this topic, further evaluation of the efficacy and safety of MISP and EEP is necessary.

We conducted a meta-analysis of clinical studies comparing MISP and EEP in terms of short-term efficacy, perioperative outcomes, and complications. According to the review criteria, 8 comparative trials involving 1,504 patients with large BPH were determined. The quantitative analysis demonstrated that the two surgical procedures had similar 3- and 6-month IPSS, 3- and 6-month Qmax, 3-month PVR, and 3-month QoL. Our findings are broadly consistent with previously published literature. This suggests that even though there are some differences between the different surgical procedures, they appear to be equally effective for treatment of large BPH (19). Furthermore, it should be noted that we also observed that EEP had a superior 6-month PVR (only two studies involved), but this conclusion needs to be confirmed in high-quality randomized controlled trials (RCTs) with longer follow-up.

In this meta-analysis, we found that EEP might have superior perioperative outcomes. Compared with the MISP group, the EEP group had a shorter operation time, less Hb decrease, shorter catheterization time, lower LOS, and comparable resection weight. Our results are consistent with the existing evidence comparing the two surgical methods (12, 15, 19). Interestingly, subgroup analysis revealed that when the two minimally invasive techniques were separately compared with endoscopic surgery, the operative time was higher for LSP (p = 0.009) and comparable for RASP (p = 0.08). Nevertheless, there was significant heterogeneity in these studies. Baldini et al. (13) and Fuschi et al. (17) reported that there was no difference in operative time between LSP and endoscopic procedure. In contrast, Gunseren et al. (18) observed that LSP was associated with higher operative time. They claimed that closing bladder incisions could lead to a partial increase in operative time, even in the hands of surgeons with laparoscopic experience. Further correlation line demonstrated that the operative time advantage of holmium laser enucleation of the prostate (HoLEP) might disappear in huge prostates. For comparison of RASP and endoscopic procedure, Zhang et al. (15) found that RASP had a higher operative time, while a prospective randomized study by Fuschi et al. (17) showed no difference in operative time between the two procedures. On the side, Fuschi et al. (17) also reported that RASP had comparable operative time to LSP.

The technical proficiency of the surgeon appears to be a factor affecting the duration of operation (8). Johnson et al. (21) found that the median operative time of RASP improved significantly as surgeons became more skilled (early cohort 160 mins vs. late cohort 134 mins). In addition, they also claimed that a physician with experience with robotic radical prostatectomy might need only 10–12 cases to become proficient with RASP. Nevertheless, surgeries that involve EEP, such as the HoLEP technique, still have a steep learning curve for even experienced surgeons (22). Brunckhorst et al. (23) reported that HoLEP required 40–60 cases to achieve a proficient efficiency platform. In consequence, the “learning curve” factor might be more favorable to RASP rather than HoLEP, but it still needs to be validated in high-quality, multicenter RCTs.

We found that the EEP had a lower Hb decrease compared to MISP. In fact, both procedures rely on direct application of energy to achieve intraoperative hemostasis, but the endoscopic method can control the bleeding rapidly during the enucleation and thus has a better hemostasis effect (15). In most cases, fewer bleeding may be associated with surgical parameters such as shorter catheterization time and lower LOS, so the EEP group might have shorter catheterization time and LOS (24). However, there were significant differences in the results of different studies. Lusuardi et al. (12) reported a lower Hb decrease in endoscopic surgery, whereas Umari et al. (14) and Lombardo et al. (19) did not observe such a significant difference. In addition, higher hemoglobin reduction did not translate into higher blood transfusions. We observed similar blood transfusions between the groups (7.4 vs. 3.1%, p = 0.24). Interestingly, the RASP subgroup had a higher rate of transfusion (P = 0.004). However, the transfusion rate may not be a good indicator for evaluating the outcome of minimally invasive surgery as they vary from among hospitals, according to patient comorbidities and surgeon preferences (25).

The present study also expanded the pooled evidence to show that the MISP group had comparable overall complications (p = 0.62) compared to the EEP group. Our subgroup analysis also indicated that there was no difference in overall complications between minimally invasive techniques (LSP and RASP) and endoscopic procedures. These results are consistent with the available evidence. In most studies, the incidence of related complications was low and appeared to be evenly distributed in the MISP and EEP groups. Overall, both MISP and EEP are safe surgical procedures for the treatment of large BPH, and no clear conclusions can be drawn in favor of endoscopic therapy.

Another major constraint on the widespread use of surgical techniques is cost. Juaneda et al. (26) observed an average savings of €1835 for HoLEP compared to LSP (€2871 vs. €4706), and proposed that the reduced cost of the HoLEP was associated with shorter LOS. Unfortunately, no studies have reported a cost comparison between RASP and HoLEP, but in the comparison between RASP and OSP, Matei et al. (27) found that the average cost of RASP was €3940. Besides, Sotelo et al. (28) noted that the mean cost of the RASP was $1627 more expensive than LSP. These results suggest that endoscopic procedures appear to be cheaper than MISP. However, cost-benefit analysis is extremely complex and is influenced by many factors, such as hospital costs, complications, and reimbursement issues, which vary widely between countries and healthcare systems (25). Therefore, carefully designed studies are needed before definitive conclusions can be drawn.

Compared with the study of Abi Chebel et al. (20), the present meta-analysis has the advantage of including three recent comparative trials and then analyzing more parameters related to the effectiveness and safety of these two methods. In addition, the previous study only provided 3-month IPSS data, whereas our study expanded the sample size and further evaluated functional outcomes at 6-month. Another strength of the current study was our subgroup analyses, which for the first time systematically compared RASP with EEP outcomes.

Limitations should be noted before interpreting our findings. First, this study was unable to analyze the learning curves and costs of the two processes because of the lack of data. Second, significant heterogeneity was observed in perioperative outcomes and complications, which may limit the strength of our evidence. For this, we conducted a subgroup analysis of each outcome indicator based on the minimally invasive approach, hoping that this has increased some robustness to our analysis and interpretation. Third, the follow-up time was mostly less than 6 months. Therefore, our results can only compare the short-term efficacy and safety of MISP and EEP. Finally, due to the inconsistent follow-up time in this study, there may be deviations in the reports of complications.

The current study suggested that the short-term efficacy and safety were comparable between MISP and EEP procedures for large prostates. However, EEP may have a more favorable perioperative profile with shortened operative time, reduced Hb decrease, shortened reduced catheterization time, and reduced LOS. Based on these results, both surgical procedures could be offered to patients, which should understand the advantages and disadvantages of each method to make a suitable decision.

The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the Corresponding Author/s.

QW is responsible for manuscript conceptualization. JL, DC, and CM are responsible for manuscript writing and data analysis. LP and ZX are responsible for data analysis. YL and QW are responsible for manuscript editing. All authors contributed to the article and approved the submitted version.

This work was supported by the National Natural Science Foundation of China (Grant Number 82000721), Post-Doctor Research Project, West China Hospital, Sichuan University (Grant Number 2019HXBH089), Health commission of Sichuan province (Grant Number 20PJ036), and Sichuan Province Science and Technology Planning Project (Grant Number 2020YJ0054 and 2020YFS0320).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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