A Comparative Study on the Therapeutic Effect of en Bloc Transurethral Resection of Bladder Tumors with Needle Electrode and Traditional Transurethral Resection of Bladder Tumor on Non-Muscle Invasive Bladder Tumor

En bloc transurethral resection of bladder tumors (ERBT) as an improved method of traditional transurethral resection of bladder tumor (TURBT), has not been standardized. The purpose of this study is to evaluate the safety and effectiveness of the technology. We divide non-muscle invasive bladder cancer into an experimental group receiving ERBT and a control group receiving traditional TURBT, and compared the recurrence rate by Kaplan-Meier curve adjusted by propensity score matching (PSM) analysis. In addition, we analyzed the independent risk factors affecting the recurrence rate of NMBIC by COX risk regression.

follow-up data of patients with NMIBC treated in our department from February 2016 to February 2020 were collected. The patients who received ERBT were included in the experimental group, and the patients who received TURBT were included in the control group. The treatment effect and recurrence rate of the two groups were compared to evaluate the technical safety and effectiveness.

Patients enrollment
From February 2016 to February 2020, clinical data of 212 patients with NMIBC who received bladder cancer treatment in the Department of Urology, Lanzhou University.
Exclusion criteria: 1) The tumor has invaded the ureter, prostate, and urethra; 2) Postoperative diagnosis of muscle invasive bladder cancer and above; 3) History of chemotherapy before surgery.
In the end, a total of 212 patients who met the criteria were included in this study, including 39 in the experimental group and 173 in the control group.

Treatment
Experimental group: The patient was placed in lithotomy position after anesthesia, the irrigating solution was saline, the surgical area was disinfected, and sterile cloth were placed. Visually place the resectoscope into the bladder to determine the number, size and location of the tumor. First mark a circle with a needle electrode at the normal mucosa of 0.5 to 1 cm around the root of the tumor, and then electrocut the mucosa to the bladder muscle layer, surround the root of the tumor, and completely cut the tumor. The hemorrhage was stopped by electrocoagulation mode. If the tumor is small, it is ushed out with a irrigator. When it is di cult to ush out, it is taken out with gripping pliers. When the tumor is too large, divide the tumor body 2-3 times before rushing out of the tunnel. Finally, a part of the tissue was taken from the wound surface as a base specimen. F22 three-lumen urinary catheter was placed after operation.
Control group: The patient was placed in lithotomy position after anesthesia, the irrigating solution was saline, the surgical area was disinfected, and sterile cloth were placed. Visually place the resectoscope into the bladder to determine the number, size and location of the tumor. Use a spade electrode to remove the tumor layer by layer, cut to the muscular layer. The hemorrhage was stopped by electrocoagulation mode. Finally, a part of the tissue was taken from the wound surface as a base specimen. Use the irrigator to ush out the tumor tissue fragments, and leave the specimens for examination. F22 threelumen urinary catheter was placed after operation.
Postoperative bladder infusion: All patients undergo bladder instillation after operation. Infusion drugs include cytotoxic drugs and immunologic agents. Cytotoxic drugs include epirubicin, pirarubicin, gemcitabine, etc.; individual patients choose immunologic agents, such as BCG. Method: Once a week (9 times). Treatment: Initially once a week (10 times), then once a month (10 times).

Data collection
By reading the patient's medical records, we collected the following data: the patient's baseline treatment

Statistical analysis
Pearson χ 2 or Fisher exact test (for categorical data) and independent sample t test (for continuous variables) were used to evaluate the association between treatment methods and patient characteristics and clinical characteristics. In order to reduce the bias of non-random treatment allocation, we used the propensity score matching (PSM) method. All baseline covariates were considered, including age, gender, tumor size, tumor number, pathological grade, tumor stage, receiving repeat TURBT, and year of diagnosis. For PSM, ERBT-treated patients were matched 1:1 with traditional TURBT-treated patients with a propensity score of 0.05 calipers.
In this model, Kaplan-Meier curves are used to calculate the overall recurrence rate. Univariate and multivariate Cox models were conducted to compare groups in PSM analysis. P value <0.05 was considered statistically signi cant. Statistical analysis was performed using Statistical Product for Social Sciences (SPSS) software (version 24.0).

Result
Patients' characteristics From 2016 to 2020, a total of 212 patients with NMIBC were included in the study, of which 39 patients received ERBT and 173 patients received traditional TURBT. The patient's baseline data is shown in Table 1. As shown in Table 1, before the PSM match, there is a signi cant difference between the two groups in receiving repeat TURBT. After PSM matching, there were no signi cant differences between the two groups of factors.

Survival analysis
The median follow-up time for the entire study was 21 months (2-51 months). In this study, the total recurrence rates of the experimental group and the control group were 15.4% and 23.7%(P = 0.592), respectively. The 6-month recurrence rate was 10.3% and 8.1%, the 1-year recurrence rate was 12.8% and 13.9%, and the 3-year recurrence rate was 15.4% and 22.0%, respectively. (Fig. 1A, Table 2). The results of multivariate analysis showed that pathological grade, tumor size, and tumor number were independent risk factors affecting patients' recurrence (Table 3). In the head-to-head PSM analysis, 33 patients receiving ERBT treatment and 33 patients receiving traditional TURBT treatment were successfully matched, and the age, gender, tumor size, tumor number, pathological grade, tumor stage, receiving repeat TURBT were balanced between the two groups ( Table 1). multivariate analysis results are shown in Table 4. The total recurrence rates of the experimental group and the control group were 18.2% and 24.2%, respectively (P = 0.226). The 6-month recurrence rate was 12.1% and 15.2%, the 1-year recurrence rate was 15.2% and 18.2%, and the 3-year recurrence rate was 18.2% and 24.2%, respectively. (Fig. 1B, Table 2).

Disease progression
Of the 212 patients, 15 patients had disease progression (clinical stage or pathological grade progression). Among them, 1 case was in the experimental group and 14 cases were in the control group. The progress rates were 2.6% and 8.1%, respectively (P = 0.224). After PSM matching, the progress rates of the two groups were 3.0% and 9.1% (P = 0.302). At the same time, for high-grade tumors, the progression rates of the two groups before PSM were 11.1% and 10.8% (P = 0.979), and the progression rates of the two groups after PSM were 11.1% and 13.3% (P = 0.873). As shown in Table 5.

Comparison of perioperative conditions
This study collected perioperative data of 212 patients, including operation time, intraoperative hemorrhage, intraoperative complications, postoperative fart time, bladder irrigation time, and catheterization time ( Table 6). As shown in the table, the two groups differed in intraoperative blood loss and catheterization time. After PSM matching, the two groups only had statistical differences in intraoperative bleeding (P = 0.04).

Postoperative pathology results
In this study, 212 patients were diagnosed with non-muscle invasive urothelial carcinoma, 166 cases of low grade (30 cases in the experimental group, 136 cases in the control group), 46 cases of high grade tumors (9 cases in the experimental group, 37 cases in the control group). The detrusor muscle tissue was found in the postoperative pathology of all patients in the experimental group. In the control group, 15 patients were not found to have detrusor muscles (8.6%). After PSM matching, 3 patients in the control group had no detrusor muscles (9.1%) in their postoperative pathological tissues. Moreover, the edge of the pathological tissue in the experimental group was clear and there were few burn marks, while the edge of the pathological tissue in the control group showed more serious burn marks.

Discussion
The incidence of bladder cancer is increasing year by year, and surgery is its main treatment strategy.
Until today, ERBT technology has been widely accepted by clinicians. In addition, a variety of ERBT technologies have been invented [8][9] . However, ERBT does not have a de nite standard. Moreover, its e cacy with traditional TURBT is also controversial. At present, random comparison of ERBT with needle electrode and traditional TURBT is rare in clinic.
Our approach based on propensity score matching directly compared the therapeutic bene ts of ERBT and traditional TURBT. After 1:1 matching, there was no statistically signi cant difference in the recurrence rate between the two groups (P = 0.226). One study suggested that ERBT can avoid tumor fragmentation, thereby minimize the oating of tumor cells, reducing the risk of recurrence of tumors 4 .
However, we did not nd that ERBT showed an advantage in terms of recurrence rate and progression rate. This is consistent with the results of some literature published in recent years. Zhang et al 10 compared 90 patients with NMIBC treated by transurethral resection of bladder tumors (40 in the ERBT group and 50 in the traditional TURBT group), and found that there was no difference in the total recurrence rate between the two groups (20% vs 24%, P = 0.650). In addition, a study 11 compared ERBT with 1.9 microm vela laser and traditional TURBT, and there was no difference in recurrence rate between the two groups (P > 0.05). However, an randomized controlled trial 12 believes that although the recurrence rate at the same location is similar in the ERBT group and the TURBT group (4.9% vs 7.5%, P > 0.05), the ERBT group has a clear advantage in terms of overall recurrence rate ( 17.1% vs 27.5%, P<0.05). Therefore, in terms of recurrence rate, whether ERBT can achieve better e cacy than the traditional TURBT group requires more experiments to prove. In terms of progression rate, this study found that although the results of the two groups were not statistically different, when the factor of tumor grade was limited, the difference in progression rate between the two groups was signi cantly reduced. It can be seen that tumor grade seems to be a factor affecting tumor progression.
In terms of surgical effect, we compared the effects of two different surgical methods on operation time, intraoperative hemorrhage, intraoperative complications, postoperative fart time, bladder irrigation time, and catheterization time, etc. The results showed that the ERBT group had an advantage in intraoperative bleeding compared with the traditional TURBT group (P = 0.04). We believe that during the ERBT operation, the tumor is usually removed from the surrounding tumor and advanced to the root of the tumor, so that the blood vessels around the tumor can be cut off and hemostasis can be stopped in time, which allows a better visual eld during surgery and bleeding Also less. In the study by Balan et al 12 , compared with the traditional TURBT group, the ERBT group had a lower drop in hemoglobin (0.28 vs 0.76 g/dL, P < 0.05). It can be seen that ERBT does have an advantage in improving intraoperative bleeding. Some articles reported that ERBT can effectively reduce the time of ushing, catheterization and hospitalization [12][13][14] , but in our study, no differences were found between the two groups. In terms of surgery time, some studies believe that ERBT takes less time (13.4 vs 19.7 min, P < 0.05) 12 , and some studies nd that ERBT takes longer surgery time (40.0 vs 19.5 min, P = 0.0002) 13 . In our opinion, the operation time is mainly related to the experience of the surgeon doctor and the surgical instruments used. In this study, the surgeon doctor has extensive experience in surgery. At the same time, we use needle electrodes as a resection tool, which has a small contact surface with the tissue, which effectively reduces the time spent adjusting the position. Of course, the small contact area will slow the rate of resection, therefore, we did not nd a difference in surgical time between the two groups. After PSM matching, we found that there were no surgical complications in the two groups of patients. Analyzing the data before matching, there was no difference in obturator nerve re ex between the two groups. This seems to be contrary to some research results 12,15 . However, reading of the relevant literature carefully reveals that the traditional TURBT energy source in this type of research is a plasma monopolar source, while our traditional TURBT group energy source is a plasma bipolar electrode. In theory, the use of bipolar energy can reduce the risk of obturator nerve re exes. Avallone et al 16 compared the safety and e cacy of monopolar and bipolar energy TURBT in the treatment of NMIBC, and found that the use of bipolar energy has a tendency to reduce obturator nerve re exes (2.6% vs 5.8%).
Research suggests that the presence of detrusor muscles is an important surgical quality control indicator used to indicate complete tumor resection 17 . The results of Zhang et al 10 showed that the presence of detrusor muscle was easier to nd in the pathological tissue after ERBT (100% vs 54%, P < 0.01). Another study also recognized the advantages of ERBT in this regard (2.94% vs 20.0%, P = 0.04) 18 .
In this study, we also found that the pathological tissue after ERBT seems to be easier to nd the detrusor muscle (100% vs 90.9%), however, statistical analysis did not nd a difference between the two groups. In our analysis, this may be due to the fact that the two surgical procedures in this study both excised the tissue from the surgical wound and left it as the base specimen, which can effectively nd the detrusor muscle. Comparing the postoperative pathological results of the two groups, ERBT can obtain higherquality tumor specimens, especially less burn marks on the muscle layer, which is very bene cial for postoperative evaluation of the depth of tumor invasion.
In multivariate analysis, we found that tumor grade and tumor size are risk factors affecting tumor recurrence rate, which may be due to two factors related to postoperative tumor residuals. Hayashida et al 20 proposed a new scheme combining endoscopic mucosal resection (EMR) and ERBT. EMR is used to remove the part of the tumor that protrudes from the mucosa, and use ERBT to remove the remaining part. And compare the recurrence rate of this surgical method with traditional TURBT. The results showed that there was no difference in the recurrence rate between the two groups (P = 0.662). In addition, the postoperative pathology of the new surgery can determine the degree of in ltration, while 19.4% of patients in the traditional group cannot determine the degree of in ltration (P = 0.016). Therefore, it seems to be a feasible method to segment tumor samples properly.

Conclusion
En bloc transurethral resection of bladder tumors with needle electrode is used as a treatment method for bladder tumor. Compared with traditional TURBT treatment, it has less intraoperative bleeding and high surgical safety. Moreover, this technique can obtain high-quality pathological specimens, which has obvious advantages in postoperative pathological assessment. Each author has participated su ciently in the work and takes public responsibility for appropriate portions of the content. The authors have agreed to be accountable for all aspects of the work and ensure that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. JSL is the author of the article and the main collector of data. PFS as the instructor to make appropriate revisions to the article. YDH helps data collection. YCS helps data collection. XZ helps data collection. Funding: Key Science and Technology Foundation of Gansu Province Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.