ABBREVIATIONS          

AUA: American Urology Association

BCa: Bladder carcinoma

EAU: European association of urology

Holmium Laser En Bloc resection of bladder tumor (HoLERBT)

MIBC: Muscle Invasive Bladder Cancer

NMIBC: Non- Muscle Invasive Bladder Cancer

SUO: Society of Urologic Oncology

Thulium Laser En Bloc resection of bladder tumor (ThuLERBT)

TUR: Trans Urethral Resection

TURBT: Trans Urethral Resection of Bladder Tumor

UC: Urothelial Bladder Cancer

YAG: Yttrium-Aluminum-Garnet

INTRODUCTION

Bladder cancer (BCa) is the seventh most frequently diagnosed cancer in men worldwide, and it is the tenth when both male and female are considered. 75% of patients with bladder cancer manifest with disease confined to the mucosa (Ta, CIS) or submucosa (T1) [1]. Because of frequent recurrences, all patients with NMIBC need surveillance cystoscopy based on risk stratification. Initial evaluation includes radiological imaging (Ultrasonography or abdominal CT scan with contrast) and urinary cytology. Transurethral Resection of Bladder Tumor (TURBT) is the preliminary staging cum treatment for BCa. Further treatment is guided by risk stratification which is dependent on the histopathology report and findings of the initial TURBT. Proper T-stage interpretation of the lesion will depend on the inclusion of detrusor muscle in the specimen.

Conventional TUBRT, considered as the gold standard technique, thus plays the central role in guiding therapy. However, there are concerns about oncological safety of the conventional TURBT technique and inadequacy of pathological reporting of the TURBT specimen. TUBRT involves piecemeal removal of the tumor which violates the oncological principle of en bloc resection. TURBT specimens are invariably fragmented and have poor anatomic orientation. These inherent shortcomings in TURBT specimens are an impediment to accurate pathological staging owing to interobserver variability. A significant risk of under staging to the tune of 36-51% has been reported in the literature specially for the patients whose specimens do not include the muscularis propria [2-4]. Therefore, it is theoretically obvious that any en block specimen of the tumor rather than the fragmented chips will help the pathologist with better orientation and thus result in fewer errors in T-staging of the tumor. Hence, there is a need for a restaging TURBT in many situations especially for T1 tumors or any lesion that is high grade [5].  Additionally, TURBT results in liberation of a larger number of viable tumor cells in the bladder leading to a very high rates of recurrence [6]. Lateral wall tumors pose an additional challenge in the form of a obturator nerve reflex (ONR) (more prevalent with conventional TURBT performed with monopolar electric current) which can further lead to bladder perforation. These inherent flaws of TUBRT combined with a greater occurrence of complications like bleeding and obturator jerk prompted the search for alternative procedures such as laser surgery. Holmium laser generates steam bubbles in the irrigant at the fibre tip, dividing the tissue layers by tearing them apart and concurrently achieving hemostasis. At a wavelength of 2140 nm, the penetration depth of holmium laser is about 0.3-0.4 mm which is reasonably safe. This pulsed wave laser is used for tissue ablation, cutting and coagulation. The primary advantages of holmium laser include better hemostasis, resection in saline, en bloc resection and lower incidence of bladder perforation and ONR [7,8]. Zhu et al compared the recurrence rate and duration of catheterization in 212 patients with NMIBC undergoing TURBT and HoLERBT and found no difference. However, shorter operative duration was seen in the TURBT group [9].

ThuLERBT involves en bloc resection of bladder tumor using double wavelength Thulium laser. It also offers a hemostatic enucleation of tumor through bladder musculature as well as coagulation of floor of resection. There is an added advantage of decreased thermal damage (only 0.2 mm depth of thermal damage) to surrounding normal tissues in Thulium laser enucleation thus allowing for improved tumor histopathological staging.  Thulium en bloc resection also offers an added benefit of specimen orientation hence making pathohistological reporting more accurate by reporting the depth of invasion. The other advantage of Thulium laser enucleation include reduction in obturator jerks, postoperative bladder irrigation and better hemostasis [10].

In a retrospective study, Zhong et al compared the efficacy and safety of 2-micron continuous wave laser resection of non-muscle invasive bladder tumour (NMIBT) to holmium laser resection of bladder tumour (HoLRBT) and conventional transurethral resection of bladder tumour (TURBT). Compared to TURBT and HoLRBT, the two-micron laser group was associated with a decrease in haemoglobin concentration that was less severe, while other complications were similar among groups. The recurrence rates of the three groups lacked statistical significance. [11]

210 patients were enrolled and evaluated for the safety and efficacy of conventional monopolar transurethral resection of bladder tumour (TURBT), 2-micron continuous-wave laser, and holmium laser resection techniques in the management of primary non-muscle-invasive bladder tumour by Huang et al. Laser groups had fewer intraoperative and postoperative complications, including obturator nerve reflex, bladder perforation, and postoperative bladder irritation, than conventional TURBT groups. Catheterization and hospitalisation times were shorter for patients in the laser group compared to the conventional TURBT group. There were no significant differences between the three groups in terms of blood transfusion rate, incidence of urethral stricture, or recurrence of the tumour. In addition, there were no statistically significant differences between 2-micron laser and holmium laser [12] It remained unclear whether EBR’s non-scattering approach reduces infield, outfield, or overall recurrence. Nonetheless, a trend towards lower recurrence rates after EBR had been observed, although the available data didn’t allow definitive inferences [13]. 

As per these published results it is obvious that the peri-operative complication rates of conventional TURBT may be higher or similar than the laser resection but the pathological staging seems more accurate with laser therapy. En bloc resection of tumor is likely to include detrusor muscle in the specimen thereby increasing the accuracy of T-staging of tumor as compared to conventional TURBT. The advantages of Tm:YAG versus Ho:YAG, with respect to surgical and oncological outcome is yet to be proven due to lack of  well-designed prospective or RCT study in this context. Hence, the current study is planned to assess the Safety and efficacy of Holmium Laser En Bloc resection of bladder tumor (HoLERBT) and Thulium Laser En Bloc resection of bladder tumor (ThuLERBT) in Non-Muscle Invasive Bladder Cancer.

REVIEW OF LITERATURE

Globally, bladder cancer is the 7th most common malignancy and the commonest urinary system neoplasm [14]. The predominant histological type is Urothelial (previously known as transitional cell). Although mortality is comparatively low, chronicity is a real issue due to frequent recurrences. Urothelial Bladder Cancer (BCa) is usually diagnosed in the elderly, median age being 73 years. [15]

The risks of bladder cancer appear to vary across world regions, correlating with smoking and occupational exposures to carcinogens in developed countries, and with chronic bladder urothelial irritation from Schistosoma hematobium infection in Africa and the Middle East [16].

Presenting complaint classically includes painless hematuria (macroscopic or microscopic). Alternatively, irritative symptoms such as dysuria, frequency or urgency could be the presenting complaints. Irritative voiding symptoms (frequency, urgency, dysuria, or urge incontinence) are more common and highly suggestive of bladder CIS. Pain and constitutional symptoms associated with BCa usually indicate locally advanced or metastatic disease.

Initial evaluation of a suspected case of bladder cancer includes radiological imaging, urinary cytology and cystoscopy. BCa is staged using the eighth edition (2017) of the tumor, node, metastasis (TNM) classification. Close to 75-85% of the cases are restricted to the mucosa or submucosa, which is described as NMIBC. NMIBC includes Ta (noninvasive papillary), T1 (invades lamina propria), and Tis (CIS), at 70, 20, and 10 percent, respectively. [14]

If the initial evaluation is suggestive of muscle-invasive disease, cross-sectional study with Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) is indicated to identify the extent of pelvic disease, lymph node status and to rule out distant metastases.

For NMIBC, the initial treatment is a complete TURBT with sufficient depth such that muscularis propria is included. Unhealthy areas in the neck of bladder and prostatic urethra and areas of suspected CIS should also be biopsied. BCa can be classified as low grade or high grade on the basis of nuclear anaplasia and architectural abnormalities (according to the World Health Organization (WHO) and International Society of Urological Pathology (ISUP) classification). Pathological ‘T’ stage and grade along with cystoscopic findings (which includes number, size and morphology of the lesions) form the basis of risk stratification and subsequent management of patients with NMIBC.

The 2023 European Association of Urologists (EAU) guidelines stratify the risk into low, intermediate, high and very high risk. Only one of the two classification systems (WHO 1973 or WHO 2004/2016) is to be used. If both classification systems are available for a single patient, the Panel recommends using the WHO 1973 risk group calculation because it provides a more accurate prognosis. Patients with PUNLMP-classified tumours are also included in the category of LG tumours (WHO 2004/2016).  Additional clinical risk factors include age greater than 70, multiple papillary tumours, and tumour diameter greater than 3 centimetres. [17]

New EAU NMIBC prognostic factor risk groups based on the WHO  2004/2016 or the WHO 1973 grading classification systems:

Low Risk-

A primary, single, TaT1 LG/G1 tumour < 3 cm in diameter without CIS in a patient < 70 years

A primary Ta LG/G1 tumour without CIS with at most ONE of the additional clinical risk factors

Intermediate Risk-

Patients without CIS who are not included in either the low-, high-, or very high-risk groups

High Risk-

All T1 HG/G3 without CIS, EXCEPT those included in the very high-risk group

 All CIS patients, EXCEPT those included in the very high-risk group

Stage, grade with additional clinical risk factors:

• Ta LG/G2 or T1G1, no CIS with all 3 risk factors

• Ta HG/G3 or T1 LG, no CIS with at least 2 risk factors

• T1G2 no CIS with at least 1 risk factor

Very High Risk

Stage, grade with additional clinical risk factors:

• Ta HG/G3 and CIS with all 3 risk factors

• T1G2 and CIS with at least 2 risk factors

• T1 HG/G3 and CIS with at least 1 risk factor

• T1 HG/G3 no CIS with all 3 risk factors

Probabilities of disease progression in 1, 5 and 10 year(s) for the new EAU NMIBC risk groups Low (0.12%, 0.57%, 3.0%), Intermediate (0.65%, 3.6%, 7.4%), High (3.8%, 11%, 14%), and Very High (20%, 44%, 59%) respectively according to the New Risk Groups with WHO 1973) [17].

While risk stratification have been established by the American Urological Association (AUA,2021) categorizes into three groups Low, Intermediate and High which differs from updated EAU 2023 guidelines [18].

Lesions of low-grade Ta recur between 50% and 70% of the time and progress in less than 5% of cases. In comparison, high-grade T1 lesions recur in over 80% of instances and progress in 50% of patients within three years. This behaviour is grade-dependent rather than stage-dependent: high-grade tumours progress with the same frequency whether they were invasive (T1) or noninvasive (Ta) [19].

Guidelines for the treatment of Ta/T1 tumours and carcinoma in situ according to risk stratification:

EAU low risk group- One immediate instillation of intravesical chemotherapy after TURB.

EAU intermediate risk group - It is recommended that all patients receive either a 1-year full-dose BCG treatment (induction + 3-weekly instillations at 3, 6, and 12 months) or chemotherapy instillations (the optimal schedule is unknown) for a maximum of 1 year.

The final selection should be based on the patient’s risk of recurrence and progression, as well as the efficacy and adverse effects of each treatment modality. Patients with small papillary recurrences detected more than one year after a previous TURBT should receive an immediate chemotherapy instillation.

EAU high-risk group - administer intravesical full-dose BCG for 1–3 years or RC.

EAU very high-risk group - Consider RC (radical cystectomy) and offer intravesical full-dose BCG instillations for 1–3 years to those who refuse or are unable to undergo RC. For all patients with stage T1 tumors (and select patients with Ta high grade tumors in whom the original staging surgery was inadequate), a restaging TURBT is indicated before intravesical immunotherapy is administered. Following treatment, careful surveillance is recommended for both groups of patients [17].

Conventional resection:

The most important step in the management of NMIBC is the initial TURBT. It determines the accuracy of diagnosis and guides further therapy and hence, the prognosis. TURBT aims at resecting all the visible tumors as well as obtaining tissue for histopathological diagnosis.

Resection is carried out using unambiguous movements of the loop such that adequate depth is covered to include the muscular layer but avoiding perforation and charring at the same time.

Edwin Beer first performed transurethral tumor resection in 1910 [20].  Subsequent 100 years have shown huge technological advances without changing the main idea. Traditionally monopolar current was used. The patient is placed in the lithotomy position and the procedure is usually carried out under spinal anesthesia. Resection of tumors located at the lateral wall carries the risk of stimulating the obturator nerve resulting in sudden, unexpected adduction of thigh muscle and subsequent perforation. In addition, during this procedure a high temperature (up to 400°C) is generated which leads to significant tissue damage. This thermal injury results in significant charring and subsequently faulty reporting of the stage of the tumor. Additionally, the fear of perforating the bladder often leads to superficially obtained specimen which lacks the muscularis propria in 36 to 51 % of cases. As a result, there is substantial risk of under-staging the disease which may result in suboptimal management [21].

To address these issues, bipolar current was introduced. It involves the creation of a plasma field around the resectoscope (due to ionized particles) which distorts the organic bonds. This results in the generation of much lesser temperature (less than 70ºC). It is a safer alternative for pacemaker patients. It was found to be associated with reduced duration of post-operative stay, shorter catheterization time, lesser blood loss and shorter duration of surgery. The incidence of complications like ONR and bladder perforation was also found to be lower with bipolar current [22].

TURBT technique runs opposite the oncologic approach of en bloc removal of tumor. TURBT involves piecemeal approach of tumor removal, due to which more cancer cells gets liberated in the bladder as compared to laser removal, which might explain the higher incidence of recurrence, as high as 50-70%.8 Piecemeal approach also means that the specimens obtained are invariably fragmented and have poor anatomic orientation. Hence, alternative procedures like laser surgery were developed to improve the efficacy and safety of TURBT.

Holmium laser en bloc resection of bladder tumor:

The first team to have conducted an en bloc resection of the bladder tumor using Holmium: Yttrium Aluminum Garnet (YAG) laser was in the year 2001. Smoother incision, vaporization of the tissue, and enucleation are the main advantages of holmium laser in the treatment of BCa. The improved hemostasis leading to better visibility might explain the reduced catheterization and hospitalization time. Additionally, it results in more accurate orientation and depth detection thereby aiding in correct diagnosis [23].  This may reduce the need for restaging, and re-evaluation by a second resection. The wavelength of holmium laser is 2140 nm. Owing to the strong absorption by water molecules, it has a short extinction length. At the wavelength, holmium penetrates tissue to a depth of around 400 microns which is reasonably safe. Additionally, the laser power can be tailored in accordance to the dimensions of the tumor.

A recent meta-analysis of seven clinical trials revealed that en bloc TURBT resulted in shorter stay, shorter post-operative catheterization and decreased incidence of ONR when compared to traditional approaches; without increasing the duration of surgery [24].

Thulium laser en bloc resection of bladder tumor:

The thulium laser is a continuous wave that emits at a wavelength of approximately 2013 nm, providing excellent physical properties and effect on tissues with a shallow depth (0.25 mm) of tissue penetration. It is usually generated using a 2-mm laser system with a 2013-nm laser fibre and a power of 5-15 W or 30-50 W. For the treatment of bladder cancer, thulium lasers are safe and effective. There was no significant difference between ThuLEBT and TURBT in terms of tumour progression and recurrence rates. In addition, ThuLEBT is advantageous because it permits complete tumour resection and straightforward histological evaluation of specimens [25].

Studies to support ERBT:

A European multicenter study to evaluate the safety, efficacy, and recurrence rates of electrical versus laser en bloc resection of bladder tumors done by Kramer et al have shown that En bloc resection of bladder tumors (ERBT) is safe regardless of the energy source and recurrence rates did not differ between Electrical and laser group so as complications rates [26].

A meta-analysis by Zhang et al was done to compare the safety and efficacy of en bloc transurethral resection of bladder tumor (EBRT) versus conventional transurethral resection of bladder tumor (cTURBT) in which a total of 19 studies included, of which four were RCTs, three were prospective studies and 12 were retrospective studies. The results of the analysis have shown that the EBRT had a significantly lower catheterization time, hospitalization time intraoperative and postoperative complications, and 24-month recurrence rate than those treated with cTURBT, but further emphasized that the well-designed randomized controlled trials will be needed to reevaluate these outcomes [27].

In order to assess the efficacy of en bloc resection for patients with non-muscle invasive bladder cancer (NMIBC) and determine whether a resection was necessary after the initial en bloc resection, a systematic review and meta-analysis of 8 trials were conducted. Detrusor muscle was seen in all ERBT specimens at a rate of 100%. Resection specimens had a tumour residual rate of 3.2%, and tumour upstaging was 0.3%. However, neither the rate of tumour recurrence or progression nor the 1-year recurrence-free survival (RFS) rate significantly differed between the two groups [28].

A recent RCT, conventional transurethral resection of bladder tumours (cTURBT) and ERBT were compared. The primary outcome was the presence of the detrusor muscle at the final histology, and the secondary outcomes were BC staging, T1 sub-staging, artefacts, complications, the rate of adjuvant treatment, and oncological outcomes. For ERBT and TURBT, the rate of detrusor muscle presence was not statistically significant. Comparable to one another were the rates of recurrence, complications, postoperative adjuvant treatment, catheterization time, and hospital stay. For BC staging, ERBT was not inferior than TURBT. However, ERBT considerably increased the likelihood of T1 sub-staging feasibility [29].

Studies to support Holmium Laser EBRT:

A meta-analysis about the safety and efficacy of laser treatment for BCa, the incidence of complications like bladder perforation and ONR was found to be lower with laser therapy. Furthermore, patients in the HoLERBT group had less postoperative pain and the short hospital stay [30].

Detrusor muscle sampling rate was found to be better with HoLERBT than TURBT (98% vs 62%.) in a RCT conducted by Hashem et al.  Additionally, sub staging on lamina propria invasion was possible in 68.2% HoLERBT cases, whereas it was possible in only 18.4% of TURBT cases (p<0.001).  HoLERBT group had shorter duration of catheterization and hospital stay [23].

Studies to support Thulium Laser EBRT:

A systematic review and meta-analysis of ten studies to compare the safety and efficacy of TmLRBT with transurethral resection of bladder tumor (TURBT) by Long et al have shown that TmLRBT group had a shorter length of hospital stay with fewer intraoperative complications including obturator nerve reflex and bladder perforation as well as higher rate of identification of detrusor and high-quality specimens for pathology diagnosis, hence superior safety. However, TmLRBT showed non-inferior efficacy in cancer control and overall recurrence [31].

A comparative prospective study to evaluate the safety, efficacy, and tumor recurrence after TmLRBT and TURBT was done by Badawy et al demonstrated that operation time and rate of bladder perforation as well as rate of muscle detection in the pathological specimen, was significantly lower with TmLRBT. Moreover, TmLRBT group had lower rates of tumor recurrence [32].

Studies to refute Laser EBRT:

A RCT comparing the energy source in en-bloc resection of bladder tumors by Diana et al had shown that the rate of detrusor muscle (DM) presence was comparable between the energies used and so was for the location of the lesion. Furthermore, no difference in staging feasibility among energies was found.  However, they have emphasized that for the lateral wall lesions, laser energy might be beneficial to avoid ONR.  Additionally, for lesions of the anterior wall as there is an increased risk of ERBT conversion to conventional TURBT, electrocautery might be preferred over laser in this location [33].

Recent evidence:

In a systematic review and meta-analysis of 29 studies, Yanagisawa et al emphasized that recurrence risk ratios did not differ statistically between en Bloc resection and conventional transurethral resection of bladder tumours. However, the pooled risk ratio for bladder perforation favoured en Bloc resection, as did the presence of detrusor muscle and muscularis mucosae in en Bloc-treated patients. In addition, those treated with En Bloc resection of bladder tumours had a lower rate of residual tumour at repeat transurethral resection than those treated with conventional transurethral resection [34].

EAU 2023 (updated position)

Considering the current evidence which favors the EBRT and gap in the knowledge in regard to which LEBRT (HoLEBRT Vs ThuLEBRT) is better than others is still unclear, Hence, the current study is designed to compare the two approaches of bladder tumor resection; in terms of safety and accuracy which will aid in providing optimum treatment to patients with BCa.

Aim & Objectives

Aim:

To establish the safety and efficacy of ThuLERBT in comparison with HoLERBT in patients with UB mass.

Objectives:

Primary objective

To assess the efficacy of ThuLERBT in comparison with HoLERBT in tumor histopathological staging and detrusor muscle sampling for biopsy.

Secondary Objective

To compare periprocedural complications between ThuLERBT and HoLERBT in terms of bleeding and obturator nerve jerk.

Compare the incidence of residual tumour and tumour upstaging in restage HoLERBT / ThuLERBT.

Research Question

Is ThuLERBT as efficacious and safe as in HoLERBT Non-Muscle Invasive Bladder Cancer?

Formulating null hypothesis: Both modalities are equally efficacious and safe for Non-Muscle Invasive Bladder Cancer.

MATERIALS AND METHODS

The study will be conducted in the Department of Urology and Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh

Study Duration: From July 2023 to December 2024.

Study Design: Randomized controlled trial.

Study population:

It is proposed to be a single blinded randomized controlled trial to be executed in the department of Urology, PGIMER Chandigarh during a period of one and a half year. Patient meeting the inclusion criteria will be enrolled into the study. After agreeing to participate in the study, informed consent will be obtained. Patient will be randomized into two groups using computer generated block randomization technique. Allocation concealment will be done using sequentially numbered opaque and sealed envelopes (SNOSE). All participants will be unaware of allocated group. Envelopes shall be opened by operating surgeon just before surgery. Patient allocated in Group A will undergo HoLERBT while in group B will undergo ThuLERBT. Patient will be assessed for post-operative complications till the time of discharge and will be followed up as per EAU guidelines.

Sample size calculation:

Patients presenting to Urology OPD with history of gross haematuria (suspected features of Urinary Bladder mass) will be evaluated with detailed history followed by clinical examination. They will be subjected to initial blood investigation which include hemogram, renal function tests, coagulogram, blood sugar etc.  All of them will undergo evaluation of the urinary tract by ultrasonography. If indicated CECT abdomen will also be performed. After the initial investigation patients will be included for the study if they fulfill the following inclusion and exclusion criteria.

According to previous study, the efficacy in term of detrusor muscle detection rate was from 95% to 100% in HoLERBT and ThuLERBT in non-muscle invasive bladder cancer patients [23]. In current study, we hypothesized that both treatment modalities will be equally effective in term of detrusor muscle detection rate as 98%. Hence, we will recruit 35 patients in both groups (Total 70 patients) with 10% equivalence margin and 80% power of study and two-sided 95% confidence interval. Anticipating 10% drop out rate, we will recruit 80 patients (40 in each group) in our study.

Inclusion Criteria:

Patients with Urinary Bladder mass presenting for the first time with single tumor on imaging and the tumor size less than 4 cm.

Exclusion criteria:

1)    Patients who have received any form of intravesical/systemic chemotherapy elsewhere.

2)    Patients with obvious extravesical disease on CECT (radiologically = / >T3)

3)    Tumor size more than 4 cm.

Written and informed consent will be taken before inclusion. Once they are included further work-up for fitness for anaesthesia will be carried out and these include chest X-ray, ECG, urine culture and additional blood investigation as required.

Consort Diagram

Alternate patients will be subjected to Holmium en bloc resection of the tumor under regional anesthesia. The surgery will be performed with the patient in lithotomy position. After dressing & draping, initial cystoscopy will be performed using 22Fr cystoscope sheath and a 30-degree lens. Cystoscopic findings in terms of number, location, size and morphology of the tumors will be recorded. Subsequently, HoLERBT will be carried out using 26 Fr resectoscope and saline as irrigating fluid. A 550-micrometer end firing laser fiber will be used for all HoLERBT procedures. This wire will be introduced in the working element of 26 Fr continuous flow resectoscope. The fiber will then be connected to multipulse laser system, equipped with a Holmium laser.

 Procedural Details:

HoLERBT:

We will use the following laser settings: energy 1.5-2 J, pulse 10-15 Hz, and power 15-30W. The initial step will be marking a circumtumoral incision around the bladder mass taking 2-5mm as a safety margin. After that incision will then be deepened towards deep layers as to complete en bloc resection and thus retrieve the specimen in one piece using Elik’s evacuator or grasper forceps. After retrieval of specimen, tumor base will be coagulated uniformly using pulsed wave setting of 20 W. Biopsy specimens will be sent for histopathological examination. A three-way catheter (22 Fr) will be put for bladder irrigation.In addition to cystoscopic findings, complications like bladder perforation and incidence of obturator jerk (if any) will also be noted. Post-operative haemoglobin level fall will also be recorded. The same pathologist will examine the slides for pathological reporting. Restage TURBT will be performed within 4-6 weeks of initial TURBT in case the pathology report demands it as per existing guidelines (high grade lesion or T1 lesion with or without presence of detrusor in the specimen).

ThuLERBT:

The same principles will be followed while doing Thulium Laser En Bloc resection of bladder tumor except a 550-μm fiber with 15-30/30–50 W laser settings as standard.

We will be following a grading system for both cautery artefacts and orientation of specimen, devised at our institute which is given below.

 Grading of cautery artefacts:

Grading of orientation of specimens:

Statistical analysis

·       Appropriate statistical tests will be used to analyse the data.

·       The continuous and discrete variables will be expressed as mean and standard deviation (SD)

·       Differences will be analysed with Student’s t test to compare two variables and continuous or discrete analysis of variance (ANOVA) when comparing more than tow variables.

·       The Categorical variables will be expressed as frequencies and percentages and compared with chi-square of Fisher’s exact test, depending on the frequency of expected events.

·       Differences between two groups will be considered significant at a p value of less than 0.05.