Comparison Study of Narrow Band Imaging Versus White Light Resection in Patients With Bladder Tumors/Cancer

• Sponsor: Clinical Research Office of the Endourological Society (Other)
• Overall Status: Completed
• CT.gov ID: NCT01180478
• Collaborator: (none)
• Enrollment: 965
• Arms: 2
• Duration (Months): 39

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the recurrence rate at 1 year following Narrow Band Imaging and trans-urethral resection of bladder tumor with White Light and TURB in patients with non-muscle invasive bladder cancer.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer	Device: White Light; Device: Narrow Band Imaging	N/A

Detailed Description

Currently bladder tumors are diagnosed visually with standard cystoscopy that uses white light, or light that is generated encompassing the entire visual spectrum. Some tumors such as carcinoma in situ may not be visible using white light and require patients to undergo random bladder biopsies in order to find the cancer. Recently the development of photodynamic agents have been shown to enhance these procedures to accomplish better resection and identify over-looked tumors. However, these methods often require the instillation of dyes into the bladder as well as specialized cystoscopes. Narrow band imaging (NBI) is now available which uses a special filter to limit the light to only certain wavelengths which allows the identification of areas of increased vascularity or abnormalities without the need for dyes. NBI has been investigated in gastro-intestinal disease and found to be beneficial. Early reports in urology suggest that this technology may reduce the number of tumors that are missed which could impact the recurrence rate of bladder tumors, but this is not known at this time.

Study Design

• Study Type: Interventional
• Actual Enrollment: 965 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-center, International Study to Compare Use of Narrow Band Imaging (NBI) Versus White Light(WL) During Transurethral Resection of Bladder Tumors (TURB) to Asses Recurrence of Bladder Cancer in Terms of Safety and Efficacy
• Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Other: Narrow Band Imaging Narrow Band Imaging (NBI)	Device: Narrow Band Imaging; Narrow Band Imaging
Other: White Light Trans Urethral Resection White Light Trans Urethral Resection	Device: White Light; White Light Cystoscopy

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Recurrence and Recurrence Rate at 1 Year Following Narrow Band Imaging and TURB (Arm A) Versus White Light Trans Urethral Resection of Bladder Cancer (TURB) (Arm B) in Patients With Non Muscle Invasive (pTa/T1) Bladder Cancer. [1 year after treatment]

   The primary outcome measure was recurrence rate at 1 year. A recurrence was defined as the new occurrence of a bladder cancer at the same site as or at a different site from the index cancer.

Secondary Outcome Measures

1. Number of Participants With Persistence/Recurrence of Tumors at First 3 Month Follow up After NBI Versus WL Cystoscopy and Tumor Resection [3 months after treatment]

2. Peri-operative Morbidity (30 Days) of TURB Between NBI and WL Resection Using the Clavien System. [30 days]

   Grade I Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic and radiological interventions. Grade II Requiring pharmacological treatment with drugs other than those allowed for grade I complications. Blood transfusions and total parenteral nutrition are also included. Grade III Requiring surgical, endoscopic or radiological intervention Grade III-a Intervention not under general anaesthesia Grade III-b Intervention under general anaesthesia Grade IV Life-threatening complication (including CNS complications: brain haemorrhage, ischaemic stroke, subarachnoid bleeding, but excluding transient ischaemic attacks) requiring IC/ICU management Grade IV-a Single organ dysfunction (including dialysis) Grade IV-b Multi-organ dysfunction Grade V Death of a patient

3. Risk Factors for the Development of Peri-operative Morbidity After Instrumental Treatment. [peri-operative]

   We looked at different perioperative complications in order to discover peri-operative morbidity after instrumental treatment. The following variables were analyzed: Bleeding, Fever, UTI, Bladder cramps, DVT, CVA/TIA, Lung embolism, Sepsis, Acute Abdomen, and Other perioperative complications.

4. Recurrence Rate Related to Additional Treatment Following TURB. [Until 135 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients scheduled for treatment of primary or recurrent non-muscle invasive bladder cancer

• Patients greater than 18 years of age

• No tumors in the upper tract (kidneys or ureters)

• No previous pelvic radiation

Exclusion Criteria:

• Gross hematuria at the time of resection making visualization with NBI not possible

• Participation in other clinical studies with investigations drugs concurrently or within 30 days.

• Pregnancy

• Conditions associated with a risk of poor compliance or unwilling to follow up

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Clinical Research Office of the Endourological Society

Investigators

• Study Director: Jean de la Rosette, MD, AMC University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Clinical Research Office of the Endourological Society
• ClinicalTrials.gov Identifier: NCT01180478
• Other Study ID Numbers: 10-004660
• First Posted: Aug 12, 2010
• Last Update Posted: Apr 25, 2018
• Last Verified: Mar 1, 2018

• Keywords provided by Clinical Research Office of the Endourological Society: Bladder Cancer; Urothelial carcinoma; Stage pTa or pT1; NMIBC Ta/T1; Narrow Band Imaging; White Light Cystoscopy; Transurethral resection; Superficial bladder tumor; Positive urine cytology
• Additional relevant MeSH terms: Urinary Bladder Neoplasms

Study Results

Participant Flow

Arm/Group Title	Narrow Band Imaging	White Light Trans Urethral Resection
Arm/Group Description	Narrow Band Imaging (NBI) Narrow Band Imaging: Narrow Band Imaging	White Light Trans Urethral Resection White Light: White Light Cystoscopy
Period Title: Overall Study
STARTED	484	481
COMPLETED	303	293
NOT COMPLETED	181	188

Baseline Characteristics

Arm/Group Title	Narrow Band Imaging	White Light Trans Urethral Resection	Total
Arm/Group Description	Narrow Band Imaging (NBI) Narrow Band Imaging: Narrow Band Imaging	White Light Trans Urethral Resection White Light: White Light Cystoscopy	Total of all reporting groups
Overall Participants	484	481	965
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.8 (12.5)	66.7 (12.3)	66.24 (12.41)
Sex: Female, Male (Count of Participants)
Female	94 19.4%	98 20.4%	192 19.9%
Male	390 80.6%	383 79.6%	773 80.1%
Region of Enrollment (Count of Participants)
Austria	4 0.8%	8 1.7%	12 1.2%
Canada	52 10.7%	40 8.3%	92 9.5%
China	41 8.5%	34 7.1%	75 7.8%
Czechia	51 10.5%	67 13.9%	118 12.2%
Hong Kong	23 4.8%	17 3.5%	40 4.1%
India	14 2.9%	13 2.7%	27 2.8%
Italy	3 0.6%	10 2.1%	13 1.3%
Japan	97 20%	75 15.6%	172 17.8%
South Korea	43 8.9%	48 10%	91 9.4%
Norway	13 2.7%	16 3.3%	29 3%
Romania	29 6%	30 6.2%	59 6.1%
Russia	9 1.9%	13 2.7%	22 2.3%
Spain	9 1.9%	13 2.7%	22 2.3%
Netherlands	41 8.5%	38 7.9%	79 8.2%
Turkey	38 7.9%	39 8.1%	77 8%
United States	11 2.3%	17 3.5%	28 2.9%
United Arab Emirates	6 1.2%	3 0.6%	9 0.9%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Recurrence and Recurrence Rate at 1 Year Following Narrow Band Imaging and TURB (Arm A) Versus White Light Trans Urethral Resection of Bladder Cancer (TURB) (Arm B) in Patients With Non Muscle Invasive (pTa/T1) Bladder Cancer.
Description	The primary outcome measure was recurrence rate at 1 year. A recurrence was defined as the new occurrence of a bladder cancer at the same site as or at a different site from the index cancer.
Time Frame	1 year after treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Narrow Band Imaging	White Light
Arm/Group Description
Measure Participants	484	481
Count of Participants [Participants]	104 21.5%	109 22.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Narrow Band Imaging, White Light
	Comments	The expected recurrence rate in the WL-assisted TURBT group was 35%.14 To detect a clinically relevant difference in recurrence detection rates ≥10% at a 5% significance level and a power of 80%, the required sample size per treatment was calculated to be 329 patients (658 patients in total).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.585
	Comments
	Method	Log Rank
	Comments

2. Secondary Outcome

Title	Number of Participants With Persistence/Recurrence of Tumors at First 3 Month Follow up After NBI Versus WL Cystoscopy and Tumor Resection
Time Frame	3 months after treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Narrow Band Imaging	White Light Trans Urethral Resection
Arm/Group Description	Narrow Band Imaging (NBI) Narrow Band Imaging: Narrow Band Imaging	White Light Trans Urethral Resection White Light: White Light Cystoscopy
Measure Participants	484	481
Count of Participants [Participants]	59 12.2%	61 12.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Narrow Band Imaging, White Light
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.742
	Comments
	Method	Chi-squared
	Comments

3. Secondary Outcome

Title	Peri-operative Morbidity (30 Days) of TURB Between NBI and WL Resection Using the Clavien System.
Description	Grade I Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic and radiological interventions. Grade II Requiring pharmacological treatment with drugs other than those allowed for grade I complications. Blood transfusions and total parenteral nutrition are also included. Grade III Requiring surgical, endoscopic or radiological intervention Grade III-a Intervention not under general anaesthesia Grade III-b Intervention under general anaesthesia Grade IV Life-threatening complication (including CNS complications: brain haemorrhage, ischaemic stroke, subarachnoid bleeding, but excluding transient ischaemic attacks) requiring IC/ICU management Grade IV-a Single organ dysfunction (including dialysis) Grade IV-b Multi-organ dysfunction Grade V Death of a patient
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

The Clavien grading of perioperative complications variable contains missings, therefore the valid percentages are presented in the outcome measure data table. The NBI group had 2 missing values, and the WL group had 3 missing values. Therfore, the overall number deviates from 484 and 481. Below shown is a categorical variable with 8 categories

Arm/Group Title	Narrow Band Imaging	White Light Trans Urethral Resection
Arm/Group Description	Narrow Band Imaging (NBI) Narrow Band Imaging: Narrow Band Imaging	White Light Trans Urethral Resection White Light: White Light Cystoscopy
Measure Participants	482	478
None	415 85.7%	429 89.2%
I	28 5.8%	19 4%
II	23 4.8%	21 4.4%
IIIA	11 2.3%	4 0.8%
IIIB	3 0.6%	5 1%
IVA	0 0%	0 0%
IVB	0 0%	0 0%
V	2 0.4%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Narrow Band Imaging, White Light
	Comments	The statistical analyses refers to comparison of the different 8 categories (one variable) mentioned of the Clavien grading of perioperative complications between Narrow Band Imaging and White Light Trans Urethral Resection.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.170
	Comments
	Method	Fisher Exact
	Comments	The analysis was performed by using the Fisher exact test, because the criteria for using the Chi square test were not met.

4. Secondary Outcome

Title	Risk Factors for the Development of Peri-operative Morbidity After Instrumental Treatment.
Description	We looked at different perioperative complications in order to discover peri-operative morbidity after instrumental treatment. The following variables were analyzed: Bleeding, Fever, UTI, Bladder cramps, DVT, CVA/TIA, Lung embolism, Sepsis, Acute Abdomen, and Other perioperative complications.
Time Frame	peri-operative

Outcome Measure Data

Analysis Population Description

The variables contain missing values, therefore the numbers in the below table differs from the overall numbers reported

Arm/Group Title	Narrow Band Imaging	White Light Trans Urethral Resection
Arm/Group Description	Narrow Band Imaging (NBI) Narrow Band Imaging: Narrow Band Imaging	White Light Trans Urethral Resection White Light: White Light Cystoscopy
Measure Participants	484	481
Bleeding	36 7.4%	27 5.6%
Fever	9 1.9%	7 1.5%
UTI	8 1.7%	10 2.1%
Bladder cramps	19 3.9%	10 2.1%
DVT	0 0%	0 0%
CVA/TIA	2 0.4%	0 0%
Lung embolism	0 0%	0 0%
Sepsis	2 0.4%	0 0%
Acute Abdomen	1 0.2%	1 0.2%
Other perioperative complication	9 1.9%	13 2.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Narrow Band Imaging, White Light
	Comments	Comparison of the numbers in 'Bleeding' between NBI and WL
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.311
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Narrow Band Imaging, White Light
	Comments	Comparison of the numbers in 'Fever' between NBI and WL
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.666
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Narrow Band Imaging, White Light
	Comments	Comparison in the number of 'UTI' between NBI and WL
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.569
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Narrow Band Imaging, White Light
	Comments	Comparison in the number of 'Bladder cramps' between NBI and WL
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.111
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Narrow Band Imaging, White Light
	Comments	Comparison in the number of 'DVT' between NBI and WL
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Other Statistical Analysis		Non of the participants/patients had DVT. Therefore, the p-value is not available

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Narrow Band Imaging, White Light
	Comments	Comparison in the number of 'CVA/TIA' between NBI and WL
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.500
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Narrow Band Imaging, White Light
	Comments	Comparison in the number of 'Lung embolism' between NBI and WL
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Other Statistical Analysis		Non of the participants/patients had a lung embolism. Therefore, no p-value was available

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Narrow Band Imaging, White Light
	Comments	Comparison in the number of 'Sepsis' between NBI and WL
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.500
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Narrow Band Imaging, White Light
	Comments	Comparison in the number of 'Acute Abdomen' between NBI and WL
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Narrow Band Imaging, White Light
	Comments	Comparison in the number of 'Other perioperative complication' between NBI and WL
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.170
	Comments
	Method	Chi-squared
	Comments

5. Secondary Outcome

Title	Recurrence Rate Related to Additional Treatment Following TURB.
Time Frame	Until 135 days

Outcome Measure Data

Analysis Population Description

Only 61 of the patients in the total population in the NBI group, and 69 of the patients in the total population of the WL group received a Re-TURBT after initial TURBT (within 135 days). These numbers therefore differ and deviate from the Participant Flow module.

Arm/Group Title	Narrow Band Imaging	White Light Trans Urethral Resection
Arm/Group Description	Narrow Band Imaging (NBI) Narrow Band Imaging: Narrow Band Imaging	White Light Trans Urethral Resection White Light: White Light Cystoscopy
Measure Participants	61	70
Number [participants]	27 5.6%	27 5.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Narrow Band Imaging, White Light
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.553
	Comments
	Method	Chi-squared
	Comments

Adverse Events

Adverse Event Reporting Description	Only Serious Adverse Events were monitored
Arm/Group Title	Narrow Band Imaging		White Light Trans Urethral Resection
Arm/Group Description	Narrow Band Imaging (NBI) Narrow Band Imaging: Narrow Band Imaging		White Light Trans Urethral Resection White Light: White Light Cystoscopy
All Cause Mortality
	Narrow Band Imaging		White Light Trans Urethral Resection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Narrow Band Imaging		White Light Trans Urethral Resection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/484 (5.2%)		27/481 (5.6%)
Cardiac disorders
patient died of cardiac arrest	1/484 (0.2%)		1/481 (0.2%)
patient died of heart attack	1/484 (0.2%)		0/481 (0%)
patient died of asystolia	1/484 (0.2%)		0/481 (0%)
Gastrointestinal disorders
rectorrhagia	0/484 (0%)		1/481 (0.2%)
patient died of intestinal obstruction	1/484 (0.2%)		1/481 (0.2%)
herniainguinalis	0/484 (0%)		1/481 (0.2%)
patient died of pancreas cancer	1/484 (0.2%)		0/481 (0%)
General disorders
patient died of unknown cause	2/484 (0.4%)		2/481 (0.4%)
euthanasia	0/484 (0%)		1/481 (0.2%)
Hepatobiliary disorders
galbladder carcinoma	0/484 (0%)		1/481 (0.2%)
patient died of biliary tract cancer	1/484 (0.2%)		0/481 (0%)
Infections and infestations
urinary tract infection	1/484 (0.2%)		1/481 (0.2%)
campylobacter colitis	0/484 (0%)		1/481 (0.2%)
acute prostatitis	0/484 (0%)		1/481 (0.2%)
infection of unknown origin	0/484 (0%)		1/481 (0.2%)
patient died of septicaemia	1/484 (0.2%)		0/481 (0%)
Injury, poisoning and procedural complications
patient died by car accident	0/484 (0%)		1/481 (0.2%)
obturator kick	1/484 (0.2%)		0/481 (0%)
urethral injury occurred at time of TUR	1/484 (0.2%)		0/481 (0%)
Musculoskeletal and connective tissue disorders
hip's fracture	0/484 (0%)		1/481 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
patient died of another neoplasm	1/484 (0.2%)		0/481 (0%)
patient died of cancer	1/484 (0.2%)		0/481 (0%)
Renal and urinary disorders
radical cystectomy	1/484 (0.2%)		0/481 (0%)
hydronephrosis	1/484 (0.2%)		0/481 (0%)
transurethral urethrotomy	1/484 (0.2%)		0/481 (0%)
patient died of bladder cancer	2/484 (0.4%)		5/481 (1%)
patient died by renal insuffiency and prostate cancer	1/484 (0.2%)		0/481 (0%)
transurethral resection prostate	0/484 (0%)		1/481 (0.2%)
transurethral urinary resection	0/484 (0%)		1/481 (0.2%)
patient died of kidney failure	0/484 (0%)		1/481 (0.2%)
hematuria	0/484 (0%)		1/481 (0.2%)
radical cystectomy + bricker	1/484 (0.2%)		0/481 (0%)
Respiratory, thoracic and mediastinal disorders
lung adenocarcinoma	0/484 (0%)		1/481 (0.2%)
patient died of chest infection	1/484 (0.2%)		1/481 (0.2%)
acute exacerbation of COPD	0/484 (0%)		1/481 (0.2%)
patient died of respiratory insuffiency by bilaterial pneumonia	1/484 (0.2%)		0/481 (0%)
Vascular disorders
cardiogenic embolism	1/484 (0.2%)		0/481 (0%)
cerebrovascular attack	1/484 (0.2%)		0/481 (0%)
pulmonary embolism	0/484 (0%)		1/481 (0.2%)
Other (Not Including Serious) Adverse Events
	Narrow Band Imaging		White Light Trans Urethral Resection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

There is a possibility of observer bias favouring NBI as a limitation of this single-blind study

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.