En bloc transurethral resection versus conventional transurethral resection for non-muscle invasive bladder cancer: a systematic review and meta-analysis

Introduction

Transurethral resection of the bladder tumor (TURBT) using a loop resectoscope has been the standard way of endoscopic resection for non-muscle invasive bladder cancer (NMIBC) for many decades. The classic TURBT technique is to resect the tumor in pieces by physical electrothermal effect, which not only destroys the tissue integrity of the tumor, which does not conform to the tumor-free principle, but may also cause planting or hematogenous dissemination of tumor cells (1). In 1997, Kawada et al. (2) proposed the concept of en bloc removal, removing 2.5 cm bladder tumors with modified hook electrode, which was considered to be effective and safe. The aim of this systematic review and meta-analysis was to compare the perioperative and prognostic outcomes of en bloc transurethral resection and TURBT for NMIBC. We present this article in accordance with the PRISMA reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-329/rc).

Methods

Search strategy

We conducted a systematic and comprehensive literature search across the following electronic databases: PubMed, Embase, Cochrane Library, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), WanFang Data (WanFang) and VIP Information Network (VIP). To capture relevant studies published within a defined contemporary period, the search timeframe was restricted to January 1, 2014 to December 31, 2024.

The search strategy was meticulously developed using a combination of relevant keywords, subject headings (e.g., MeSH in PubMed, Emtree in Embase), and free-text terms related to the core concepts: “non-muscle invasive bladder cancer”, “NMIBC”, “bladder tumor”, “en bloc resection”, “en bloc transurethral resection”, “conventional transurethral resection”, “TURBT”, “transurethral resection of bladder tumor”, “randomized controlled trial” and “RCT”. Boolean operators (AND, OR, NOT) were applied to combine these terms effectively. Search strategies were tailored to the specific requirements of each database.

Inclusion and exclusion criteria

The inclusion criteria included: (I) all articles were randomized controlled trials (RCTs); (II) the research object was en bloc transurethral resection and TURBT for NMIBC; (III) the outcome measures were consistent with our previous setting; (IV) full-text can be available. The exclusion criteria included: (I) studies were overview, systematic review, case, comment, animal experiments; (II) non-RCTs; (III) the research content, intervention measures, control measures or research methods are inconsistent with our design; (IV) unable to extract valid outcome data; (V) full-text cannot be available; (VI) when the same experimental results were reported at different times or in different journals, only the latest finding was included.

Quality assessment

Risk of bias was assessed independently by two reviewers, using the Cochrane risk of bias tool and Jadad score. All discrepancies between reviewers were resolved by reaching a consensus and adjudicated by a third reviewer.

Data extraction

Two reviewers independently reviewed articles and abstracted data using predefined data fields. The data we extracted included: research information (year, author, title, study type), characteristics of participants (total number of participants, age, sex, eligibility criteria), surgical and control intervention type, and outcome measures (operation time, hemorrhage, hospital stay, catheterization period, bladder irrigation time, recurrence number in 3, 6 and 12 months, the number of obturator nerve reflex, the number of vesical perforation, the number of postoperative complications, the positive number of the biopsy at the tumor base).

Data synthesis

We performed all comparison analyses using RevMan 5.3 meta-analytic software and Stata version 15. To assess the statistical significance of results, a probability of type I error of 0.05 was set. Observed treatment effect of continuous outcomes was reported as standard mean difference (SMD) with 95% confidence intervals (CIs). Observed treatment effect of categorical outcomes was reported as relative risks (RRs) with 95% CI. Heterogeneity between studies was measured using the I² statistic and P value (3). When heterogeneity (P<0.1 or I²≥50%) was significant, we explored the possible sources of heterogeneity by using sensitivity analysis, subgroup analyses and meta-regression to eliminate heterogeneity and use fixed effect model, otherwise, a random effect model was adopted. Besides, Funnel plot, Egger’s test and Beggs test were applied to evaluate publication bias (4).

Results

Summary of studies

The flow of the screening process is presented in Figure 1. Sixteen RCTs were considered eligible for inclusion, comprising 1,505 patients (experimental group: 827; control group: 678) (5-20). The details of the included studies are summarized in Table 1.

Figure 1 The selection process of the articles to compare the perioperative and prognostic outcomes of en bloc transurethral resection and TURBT for NMIBC. NMIBC, non-muscle invasive bladder cancer; RCT, randomized controlled trial; TURBT, transurethral resection of the bladder tumor.

Risk of bias assessment

Figures 2,3 showed the quality assessment outcome of each RCT using the Cochrane risk of bias 2.0 tool. No studies mentioned the method of allocation concealment. No studies used the blind method. Only one study reported incomplete outcome data. Besides, no selective outcome data or other bias was reported. In addition, we also adopt Jadad score to assess the quality of research. All studies were greater than three points, 6 of which have reached 4 points (Table 2).

Figure 2 The quality assessment outcome of each RCT using the Cochrane risk of bias 2.0 tool. RCT, randomized controlled trial.

Figure 3 The quality assessment outcome of each RCT using the Cochrane risk of bias 2.0 tool. RCT, randomized controlled trial.

Recurrence number in 3, 6 and 12 months

First, three RCTs (12,13,17), with a total of 142 participants (71 in the en bloc transurethral resection group and 71 in the TURBT group), were analyzed of the recurrence number in 3 months. The outcome indicated that no difference between en bloc transurethral resection treatment and TURBT (RR =0.14, 95% CI: 0.02–1.08, P=0.06; I²=49%) (Figure 4). Second, four RCTs (13,16,17,20), with a total of 444 participants (237 in the en bloc transurethral resection group and 207 in the TURBT group), were analyzed for the recurrence number in 6 months. The outcome indicated that the recurrence rate of en bloc transurethral resection treatment was less than TURBT (RR =0.43, 95% CI: 0.26–0.69, P<0.001; I²=0%) (Figure 5). Last, seven RCTs (5,7,9,13,18-20), with a total of 693 participants (348 in the en bloc transurethral resection group and 345 in the TURBT group), were analyzed of the recurrence number in 12 months. The outcome indicated that the recurrence rate of en bloc transurethral resection treatment was less than TURBT (RR =0.36, 95% CI: 0.25–0.53, P<0.001; I²=0%) (Figure 6).

Figure 4 A forest plot showing relative risk of the recurrence number in 3 months. CI, confidence interval; M-H, Mantel-Haenszel.

Figure 5 A forest plot showing relative risk of the recurrence number in 6 months. CI, confidence interval; M-H, Mantel-Haenszel.

Figure 6 A forest plot showing relative risk of the recurrence number in 12 months. CI, confidence interval; M-H, Mantel-Haenszel.

The positive number of the biopsy at the tumor base

Three RCTs (11,13,16), with a total of 318 participants (177 in the en bloc transurethral resection group and 141 in the TURBT group), were analyzed for the positive number of the biopsy at the tumor base. The pooled results demonstrated a lower positive rate with en bloc transurethral resection treatment compared with TURBT (RR =0.17, 95% CI: 0.07–0.43, P<0.001; I²=0%) (Figure 7).

Figure 7 A forest plot showing relative risk of the positive number of the biopsy at the tumor base. CI, confidence interval; M-H, Mantel-Haenszel.

Vesical perforation

Ten RCTs (6,7,9,11,13,14,16-18,20), with a total of 1,031 participants (534 in the en bloc transurethral resection group and 497 in the TURBT group), were analyzed for the number of the vesical perforation. The pooled results showed lower incidence with en bloc transurethral resection treatment compared with TURBT (RR =0.22, 95% CI: 0.11–0.43, P<0.001; I²=0%) (Figure 8).

Figure 8 A forest plot showing relative risk of the number of the vesical perforation. CI, confidence interval; M-H, Mantel-Haenszel.

Obturator nerve reflex

Ten RCTs (5,6,10,12,13,16-20), with a total of 1,031 participants (534 in the en bloc transurethral resection group and 497 in the TURBT group), were analyzed for the number of the obturator nerve reflex. The pooled results showed lower incidence with en bloc transurethral resection treatment compared with TURBT (RR =0.39, 95% CI: 0.18–0.83, P=0.01); however, moderate heterogeneity was found across the pooled studies (P=0.003, I²=66%) (Figure 9). Sensitivity analysis and subgroup analyses did not identify the source of this heterogeneity. We also found there was a significant publication bias using Egger’s test (P=0.03), but after we used Trim and Fill method to adjust the funnel plot, the result did not change, indicating that the results were robust.

Figure 9 A forest plot showing relative risk of the number of the obturator nerve reflex. CI, confidence interval; M-H, Mantel-Haenszel.

Postoperative complications

Four RCTs (9,13,14,16), with a total of 400 participants (216 in the en bloc transurethral resection group and 184 in the TURBT group), were analyzed for the number of the postoperative complications. The pooled results showed lower incidence with en bloc transurethral resection treatment compared with TURBT (RR =0.29, 95% CI: 0.14–0.60, P<0.001); however, moderate heterogeneity was found across the pooled studies (P=0.10, I²=53%) (Figure 10). After we used sensitivity analysis by removing one study (13), the heterogeneity was eliminated (RR =0.10, 95% CI: 0.02–0.41, P=0.002; I²=0%) (Figure 11).

Figure 10 A forest plot showing relative risk of the number of the postoperative complications. CI, confidence interval; M-H, Mantel-Haenszel.

Figure 11 A forest plot showing relative risk of the number of the postoperative complications after eliminating heterogeneity. CI, confidence interval; M-H, Mantel-Haenszel.

Operation time

Thirteen RCTs (6-10,12,13,15-20), with a total of 1,303 participants (666 in the en bloc transurethral resection group and 637 in the TURBT group), were analyzed for the operation time. The outcome indicated that no difference between en bloc transurethral resection treatment and TURBT (SMD =−0.21, 95% CI: −0.70 to 0.28, P=0.40); however, high heterogeneity was found across the pooled studies (P<0.001, I²=94%) (Figure 12), and the heterogeneity cannot be eliminated.

Figure 12 A forest plot showing standard mean difference of the operation time. CI, confidence interval; IV, inverse variance; SD, standard deviation.

Hemorrhage

Ten RCTs (6,7,9,13-15,17-20), with a total of 922 participants (462 in the en bloc transurethral resection group and 460 in the TURBT group), were analyzed for the hemorrhage. The pooled results showed less bleeding with en bloc transurethral resection treatment compared with TURBT (SMD =−2.13, 95% CI: −2.89 to −1.37, P<0.001); however, high heterogeneity was found across the pooled studies (P<0.001, I²=95%) (Figure 13). Sensitivity analysis and subgroup analyses did not identify the source of this heterogeneity. We also found there was a significant publication bias using Egger’s test (P=0.03), but after we used Trim and Fill method to adjust the funnel plot, the result did not change, indicating that the results were robust.

Figure 13 A forest plot showing standard mean difference of the hemorrhage. CI, confidence interval; IV, inverse variance; SD, standard deviation.

Hospital stay

Twelve RCTs (6-9,13-20), with a total of 1,247 participants (638 in the en bloc transurethral resection group and 609 in the TURBT group), were analyzed for the hospital stay. The pooled results showed less time with en bloc transurethral resection treatment compared with TURBT [mean difference (MD) =−2.14, 95% CI: −2.81 to −1.47, P<0.001]; however, high heterogeneity was found across the pooled studies (P<0.001, I²=93%) (Figure 14) and can’t be eliminated.

Figure 14 A forest plot showing mean difference of the hospital stay. CI, confidence interval; IV, inverse variance; SD, standard deviation.

Bladder irrigation time

Six RCTs (13,14,16-18,20), with a total of 691 participants (360 in the en bloc transurethral resection group and 331 in the TURBT group), were analyzed for the bladder irrigation time. The pooled results showed less time with en bloc transurethral resection treatment compared with TURBT (SMD =−2.80, 95% CI: −3.36 to −2.24, P<0.001); however, high heterogeneity was found across the pooled studies (P<0.001, I²=84%) (Figure 15) and can not be eliminated.

Figure 15 A forest plot showing standard mean difference of the bladder irrigation time. CI, confidence interval; IV, inverse variance; SD, standard deviation.

Catheterization period

Nine RCTs (6-9,13,14,16,17,20), with a total of 691 participants (360 in the en bloc transurethral resection group and 331 in the TURBT group), were analyzed of the catheterization time. The pooled results showed less time with en bloc transurethral resection treatment compared with TURBT (SMD =−1.77, 95% CI: −2.63 to −0.91, P<0.001); however, high heterogeneity was found across the pooled studies (P<0.001, I²=96%) (Figure 16) and can’t be eliminated. We also found there was a significant publication bias using Egger’s test (P=0.005), but after we used Trim and Fill method to adjust the funnel plot, the result did not change, indicating that the results were robust.

Figure 16 A forest plot showing standard mean difference of the catheterization time. CI, confidence interval; IV, inverse variance; SD, standard deviation.

Discussion

This study found no significant differences in operative time among the groups. Regarding the 3-month recurrence rate, it remains uncertain whether en bloc transurethral resection of bladder tumor is superior to TURBT. However, from the perspective of long-term recurrence rates, transurethral resection of bladder tumor shows greater advantages. However, in the 6- and 12-month recurrence rates, en bloc transurethral resection of bladder tumor has an advantage over TURBT. TURBT requires repeated cutting of the tumor down to the tumor base and hemostasis. This process does not conform to the principle of en bloc treatment in tumor surgery and is more likely to cause tumor dissemination. The anatomical principle of en bloc transurethral resection of bladder tumor is to completely separate the tumor from the normal detrusor muscle layer of the bladder, minimizing the tumor dissemination caused by tumor fragmentation within the bladder.

In addition, this study compared the difference in the positive rate of tumor base biopsy between TURBT and en bloc transurethral resection of bladder tumor. Since en bloc transurethral resection of bladder tumor allows the surgeon to focus more on handling the tumor base under a clear surgical field, there will be less tumor residue, resulting in a lower positive rate of tumor base biopsy in en bloc resection of bladder tumor. Moreover, a recent study has shown that en bloc transurethral resection may have advantages in postoperative pathology in determining whether the detrusor muscle is violated and the quality of histological specimens (21). Since TURBT has both diagnostic and therapeutic purposes in the management of bladder cancer, obtaining invasive information from pathological specimens is of great importance. Research indicates that the depth from the basement membrane, the number of invasive lesions, the maximum width of invasive lesions, muscularis mucosa invasion and the invasion pattern are independent prognostic factors for progression. En bloc resection helps to evaluate pathological variables that may contribute to predicting disease recurrence and progression (22). However, due to various factors, TURBT does not always guarantee high-quality pathological specimens after surgery. In contrast, en bloc transurethral resection of bladder tumor can provide more opportunities for detrusor muscle sampling while minimizing thermal damage to the tissue (23), providing a more accurate basis for further treatment and follow-up of patients after surgery. Furthermore, TURBT typically involves fragmenting the tumor along with its base and flushing them out of the bladder, or sending only the eschar from the lamina propria of the tumor base and fragmented muscle fibers for pathological examination. This often makes it difficult to provide an accurate pathological staging diagnosis. However, preoperative imaging examinations struggle to distinguish between tumor stages Tis, Ta, and T1. Therefore, the pathological staging of bladder cancer is challenging to analyze in studies on TURBT, which may confound the observed recurrence rates and other outcome measures. In addition, we have noted that the lack of information on the pathological grade of bladder cancer in all articles included in this meta-analysis has imposed certain limitations on the analysis of tumor recurrence outcomes between different surgical procedures. Due to insufficient data, meaningful subgroup analyses based on tumor stage and grade cannot be conducted, which hinders our understanding of whether the relative efficacy and safety of en bloc transurethral resection compared to TURBT differ across clinically relevant risk stratifications. In future studies, relevant prospective research is still needed to clarify the relative effectiveness of en bloc transurethral resection and TURBT across the entire risk spectrum of NMIBC.

However, the long-term oncological benefits of en bloc transurethral resection of bladder tumor remain uncertain (24). Some scholars believe that the different risk levels of tumors, the number of tumors, and whether the tumors are pedunculated are factors affecting the treatment effect of en bloc transurethral resection of bladder tumor (25). In addition, the use of different devices of en bloc transurethral resection, such as different types of lasers or electrodes with different shapes for enucleating tumors at different locations within the bladder cavity, can lead to different oncological outcomes. For example, when the tumor is located at the top of the bladder or the ureteral orifice, a needle or loop electrode can be used to lift the detrusor muscle fibers beneath the tumor before transecting them with low energy. In contrast, using laser equipment makes it more difficult to enucleate the tumor from these areas compared to needle or loop electrodes, thereby affecting the final intracavitary treatment outcome of bladder tumors. This still requires further exploration and research in the future.

We compared the bladder perforation rate and the number of obturator nerve reflexes between TURBT and en bloc transurethral resection of bladder tumor. The pooled results showed that compared with TURBT, en bloc transurethral resection of bladder tumor has fewer occurrences of bladder perforation and obturator nerve reflexes, and a lower incidence of postoperative complications. During TURBT, when using an electrode to cut tumors on the lateral wall, in order to ensure cutting efficiency, the cutting power is usually high. The electric current passes through the obturator nerve, which may stimulate the obturator nerve and cause an obturator nerve reflex. This can lead to over-cutting, which can lead to surgical complications such as bladder perforation, heavy bleeding, etc. When using an electrode for en bloc enucleation of the tumor, a combination of blunt and sharp dissection is used to separate and cut the detrusor muscle bundles of the bladder, and the cutting can be done with less current power than TURBT. The surgeon first pushes the mucosa of the tumor part and the detrusor muscle fibers below the tumor from the deep detrusor muscle fiber cross-bundles by mechanical force, and then cuts off the muscle fibers with a small cutting power in a very short time. Electrical stimulation is smaller, reducing the incidence of obturator reflexes and bladder perforation. Using a laser to enucleate tumors on the lateral wall is more effective, because there is no problem of electrical stimulation-caused obturator reflex. Currently, by summarizing different en bloc transurethral resection techniques, they have been classified into bipolar electrocautery and laser energy modes. Electro-cautery en bloc transurethral resection is widely used clinically. In large bladder tumors at different locations, it is likely to be converted into a piece-by-piece resection. En bloc transurethral resection with a laser has an advantage in preventing obturator nerve reflexes, especially for bladder tumors located on the lateral wall (26). The reduction in surgery-related complications has also led to results consistent with our study, that is, cases undergoing en bloc transurethral resection of bladder tumor are superior to those undergoing TURBT in terms of hemorrhage, average hospital stay, bladder irrigation time, and indwelling catheterization time.

The application and promotion of en bloc transurethral resection currently face multiple limitations and difficulties. On one hand, specific tumor characteristics increase the surgical difficulty: enucleation of tumors in bladder diverticula is more difficult and risky due to the lack of a detrusor muscle layer outside the diverticulum; meanwhile, if the diameter of solid bladder tumors exceeds 2 cm, specimen retrieval will be challenging (23). On the other hand, at the technical operation level, there is no conclusive evidence supporting the superiority of any specific energy source in en bloc resection. Although laser energy can avoid the activation of obturator nerve reflexes, it is accompanied by disadvantages such as thermal damage, poor controllability, expensive equipment and consumables, a long learning curve, and increased surgical time (27). In contrast, needle-shaped electrodes, despite their advantages of high precision, strong controllability, and no tissue deterioration or vaporization, have higher operational difficulty (28). However, they are more cost-effective and conducive to promotion in a wider range of areas. Given the generally long learning curve of this surgery, regardless of the energy source used, some scholars have developed ex vivo models to help urologists cross the inflection point of the learning curve more quickly (29).

Conclusions

En bloc transurethral resection was at least equivalent to TURBT for the operation time and the 3-month recurrence rate. The 6- and 12-month recurrence rate was low, as well as a low positive rate of the biopsy at the tumor base, low incidence of vesical perforation, obturator nerve reflex and postoperative complications, and a fewer incidence of hemorrhage, shorter hospital stay, bladder irrigation time and catheterization time compared with TURBT. Despite observed heterogeneity among the included studies, the findings of fewer adverse events, suggest that the en bloc transurethral resection should be the recommended treatment for NMIBC where feasible.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the PRISMA reporting checklist. Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-329/rc

Peer Review File: Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-329/prf

Funding: This work was supported by the Natural Science Foundation of Ningxia (No. 2021AAC03368) and Ningxia Medical University Project (No. XT2024038).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-329/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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