Holmium Laser En-Bloc Resection Versus Conventional Transurethral Resection of Bladder Tumors for Treatment of Non-muscle- Invasive Bladder Cancer
Phase: NA
Conditions: Bladder Tumor (TURBT)
Sponsor: Beni-Suef University

Holmium Laser En-Bloc Resection versus Conventional 
Transurethral Resection of Bladder Tumors for Treatment 
of Non-muscle- Invasive Bladder Cancer 
Protocol ID: FMBSUREC/05012025/Mahmoud 
Date: January 5, 2025 
 
Introduction 
Non-muscle-invasive bladder cancer (NMIBC) is a prevalent malignancy that poses 
significant management challenges, primarily due to the potential for recurrence and 
progression. The cornerstone of initial treatment for NMIBC is transurethral 
resection of the bladder (TURB), which plays a critical role in diagnosis, staging, 
and therapeutic intervention. However, conventional TURB (cTURB) often results 
in tumor fragmentation, complicating histopathological assessment and potentially 
impairing patient outcomes due to incomplete resection and subsequent disease 
recurrence (Matulewicz and Steinberg, 2020). 
In response to these challenges, the concept of en bloc TURB (eTURB) has emerged, 
aimed at enhancing the quality of resection by allowing for the excision of tumors 
in a single piece. This method facilitates a more accurate pathological evaluation, 
improving the assessment of tumor characteristics such as detrusor muscle 
presence—a key indicator of resection quality associated with better oncological 
outcomes. Despite these theoretical advantages, robust evidence supporting the 
superiority of eTURB over cTURB remains limited (D'Andrea et al., 2023). 
Laser en-bloc resection of the bladder tumor (LERBT) is a complete tumor resection 
technique. LERBT improves the quality of resection, reduces perioperative 
complications, and has the potential to improve recurrence rates (Hashem et al., 
2021). 

Conventional transurethral resection of the bladder tumor (CTURBT) with a 
monopolar or bipolar resectoscope obtains an inferior quality of specimen than laser 
en-bloc resection of the bladder tumor (LERBT) based on a previous meta-analysis 
study (Zhang et al., 2020). 
Recent advancements in laser technology, particularly the holmium laser, have 
introduced new treatment modalities for NMIBC. Holmium laser resection of 
bladder tumors (HoLRBT) has demonstrated promise in treating benign urological 
conditions, but its application in primary NMIBC is less understood. Existing studies 
primarily focus on recurrent cases with limited patient populations and follow-up 
durations, highlighting a significant gap in the literature regarding the long-term 
safety, feasibility, and efficacy of holmium laser in this context (Maheshwari et al., 
2020). 
Therefore, this study aims to conduct prospective randomized trial comparing 
holmium laser en bloc resection (HoLRBT) with conventional transurethral 
resection (cTURB) for the treatment of NMIBC. The primary focus will be on the 
quality of the pathological specimen, specifically evaluating the presence of detrusor 
muscle, which will provide valuable insights into the quality of the resection and its 
implications for oncological outcomes (Basile et al., 2024). 
 
 
 
 
 
 

Aim of the work 
Primary objective 
To compare the quality of resection between holmium laser en bloc resection of 
bladder tumor (HoLERBT) and conventional transurethral resection of bladder 
tumor (cTURBT) in patients with suspected non-muscle-invasive bladder cancer, as 
assessed by the presence of detrusor muscle in the resected specimen. 
Secondary objectives 
To compare perioperative and short-term oncological outcomes between both 
techniques, including: 
obturator nerve reflex 
intraoperative bleeding 
bladder perforation 
operative time 
conversion to conventional resection 
positive lateral/deep margins 
persistent disease at second-look TURBT 
recurrence at 3 and 12 months 
recurrence-free survival. 
 
 
 

Patients and Methods 
study setting: 
at Beni-Suef university hospital from 1/2025 to 1/2026 
Type of study: 
Prospective interventional study. 
study population: 
Study design 
A prospective, randomized, open-label, parallel-group controlled trial conducted at 
Beni-Suef University Hospital. A total of 100 eligible patients will be randomized 
in a 1:1 ratio to undergo either HoLERBT or cTURBT.  
Inclusion criteria 
• Adults aged 30 years or older. 
• Patients with cystoscopically suspected primary NMIBC planned for 
endoscopic resection. 
• Fit for surgery and anesthesia. 
• Able and willing to provide written informed consent and comply with follow-
up. 
Exclusion criteria 
• Muscle-invasive disease suspected preoperatively or evidence of metastatic 
disease. 
• Prior bladder radiotherapy. 
• Severe comorbidity precluding surgery. 
• Pregnancy. 
• Inability to provide informed consent. 
• Upper urinary tract urothelial carcinoma or life expectancy less than 1 year 
 

Randomization 
Randomization and allocation concealment 
Eligible patients will be randomized using a computer-generated random sequence 
in a 1:1 allocation ratio. Allocation concealment will be ensured using sequentially 
numbered, sealed, opaque envelopes prepared by an independent party not involved 
in patient recruitment or outcome assessment.  
Due to the nature of the interventions, surgeons cannot be blinded. However, 
pathological assessment may be performed by pathologists blinded to treatment 
allocation whenever feasible. 
Methods 
All patients will be subjected to: 
• Complete history taking: 
➢ Demographic information: Age, sex, occupation, marital status, 
family history 
➢ Presenting symptoms: Hematuria (frequency, duration, severity), 
urinary urgency, frequency, nocturia, dysuria, pain, retention, 
incontinence, pelvic or back pain 
➢ Past medical history: Previous surgeries (especially urological), 
bladder cancer, other malignancies, chronic conditions, 
medications, allergies 
➢ Risk factors: Smoking, occupational/environmental carcinogens, 
family history of bladder cancer, chronic infections, stones. 
 
• Complete physical examination: 
➢ General examination: 
o Vital signs (blood pressure, temperature, heart rate, respiratory 
rate) 

o General appearance and nutritional status. 
➢ Abdominal examination: o Inspection for masses or distension o Palpation for 
tenderness or masses o Percussion for dullness or tympany o Auscultation for bowel 
sounds. 
➢ Digital rectal examination: Assess for prostate enlargement or 
masses 
➢ Genital examination: Inspect for any abnormalities  
• Laboratory investigations: 
➢ Complete blood count (CBC). 
➢ Kidney function test (serum urea and creatinine). 
➢ Liver function tests (AST and ALT). 
➢ Fasting blood sugar. 
➢ Coagulation profile (PT, PTT and INR). 
➢ Urinary cytology to evaluate malignant cells. 
➢ Cystoscopy to visual inspection of the bladder 
• Imaging 
➢ Ultrasound or (Contrast enhanced) CT scan of the abdomen and 
pelvis to assess tumor extent and metastases 
➢ MRI of the pelvis may be used for further evaluation in certain cases 
Surgical procedure 
• HoLRBT Group 
 
For the HoLRBT group, a holmium laser (VersaPulse PowerSuite 100 W; Coherent 
Inc.) will be utilized under continuous epidural anesthesia. A 550-μm end-firing 
fiber, sheathed in a 5F ureteral catheter, will be delivered through a 27F continuous 
holmium resectoscope (Olympus). The laser settings will be adjusted to an energy 

of 1.5-2.2 J, a pulse rate of 15-20 Hz, and a power output of 20-40 W, with the 
possibility of modifications during the procedure. 
En bloc resection will be prioritized. First, a circular coagulation mark will be made 
approximately 1.0 cm from the tumor edge. Any obvious vessels to and from the 
tumor will be coagulated to minimize bleeding. A fan-shaped incision will then be 
made into the bladder wall until the muscle layer becomes visible. The lesion will 
be uplifted using irrigation surge, allowing for easy exposure and subsequent 
resection. Tumors ≤3.0 cm will be retrieved using a syringe, while larger tumors will 
be removed with Elik’s evacuator. After resection, careful coagulation of the tumor 
base and surrounding mucosa will be performed, and the specimen will be submitted 
for pathological evaluation as a single piece. For tumors located on the anterior 
bladder wall or dome, a combined resection and vaporization technique will be 
employed. 
• TURBT group 
In the TURBT group, a traditional piece-by-piece resection will be performed down 
to the muscle layer, with the bladder mucosa 2.0 cm away from the tumor base being 
electrocauterized. 
Follow-up and endpoints 
The primary outcome of the study will be the quality of the pathological specimen, 
measured in terms of detrusor muscle presence. 
Secondary endpoints will include the bladder perforation rate, persistent disease at 
second-look TURB, positive lateral resection margins, positive deep resection 
margins, operation time, the occurrence of obturator reflex, conversion from eTURB 
to cTURB, recurrence-free survival (RFS), and disease recurrence at 3 and 12 
months. 
Obturator reflex will be defined as an adductor spasm of the leg occurring during 
TURB. Bladder perforation will be visually assessed during the intervention. The 

severity of complications will be assessed using the Common Terminology Criteria 
for Adverse Events (CTCAE). Grade 2 will be defined as extraperitoneal 
perforation, while Grade 3 will be defined as intraperitoneal perforation. RFS will 
be defined as the time from surgery to histologically proven intravesical tumor 
relapse, last follow-up, or death. 
Sample size calculation: 
The sample size was calculated for comparison of two proportions, assuming a 
detrusor muscle presence rate of 85% in the en-bloc resection group and 60% in the 
conventional TURBT group. With a two-sided alpha error of 0.05 and a study power 
of 80%, the minimum required sample size was 49 patients per group. This was 
rounded up to 50 patients per group, resulting in a total sample size of 100 patients. 
Statistical design 
The statistical analysis will be conducted using the Software, Statistical Package for 
Social Science, (SPSS Inc. Released 2009- PASW Statistics for Windows Armonk: 
SPSS Inc. The collected data will be summarized in terms of mean ± Standard 
Deviation (SD and range (minimum - maximum) for quantitative data and frequency 
and percentage for qualitative data. The collected data will be analyzed using 
suitable statistical methods. Statistical significance will be accepted at P value <0.05. 
A P value <0.001 will be considered highly significant while a P value >0.05 will be 
considered nonsignificant. 
Ethical consideration 
➢ An approval from the Research Ethics Committee of the faculty of 
medicine will be obtained. 
➢ An informed written consent from all patients before participation will be 
obtained; it will include data about aim of the work, study design, site, 
time, subject and methods, confidentiality. 

➢ An official permission from the administrators of the defined Hospitals to 
conduct this study will be obtained. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

References 
Basile, G., Uleri, A., Leni, R., Cannoletta, D., Afferi, L., Baboudjian, M., et al. 2024. 
En Bloc Versus Conventional Transurethral Resection of Bladder Tumors: A 
Systematic Review and Meta-analysis of Oncological, Histopathological, and 
Surgical Outcomes .European Urology Oncology. 
D'Andrea, D., Soria, F., Hurle, R., Enikeev, D., Kotov, S., Régnier, S., et al. 2023. 
En Bloc Versus Conventional Resection of Primary Bladder Tumor (eBLOC): A 
Prospective, Multicenter, Open-label, Phase 3 Randomized Controlled Trial. Eur 
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Hashem, A., Mosbah, A., El-Tabey, N. A., Laymon, M., Ibrahiem, E. H., Elhamid, 
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Transurethral Resection of Bladder Tumors for Treatment of Non-muscle-invasive 
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