Trial Title:
Narrow-band Imaging Diagnostic Classification System for Bladder Tumors
NCT ID:
NCT05611762
Condition:
Urinary Bladder Neoplasms
Conditions: Official terms:
Urinary Bladder Neoplasms
Conditions: Keywords:
Urinary Bladder Neoplasms
Narrow-banding Imaging
Diagnosis
Cystoscopy
Study type:
Observational [Patient Registry]
Overall status:
Recruiting
Study design:
Time perspective:
Prospective
Summary:
The goal of this observational study is to learn about the morphological characteristics
of different bladder lesions under narrow-band imaging（NBI） techniques in All patients
requiring cystoscopy and biopsy. The main questions it aims to answer are:
1. To clarify the characteristics of different bladder lesions under NBI and to
establish a diagnostic classification system for bladder tumors under NBI based on
pathological findings.
2. Verify the accuracy of this classification system. Participants will record the
morphological characteristics under ordinary white light and NBI during cystoscopy,
analyze the pathological characteristics of different tissues corresponding to the
NBI characteristics, establish a diagnostic classification system for bladder tumor
under NBI using pathological biopsy as the diagnostic standard, and then verify the
accuracy of this classification standard through clinical.
Detailed description:
1. Background： Bladder cancer is the most common malignancy of the urinary system in
China, and its incidence is increasing year by year. Non-muscle invasive bladder
cancer (NMIBC) can mostly be removed in a minimally invasive manner by transurethral
resection of bladder tumor (TURBT), which has less impact on the patient's quality
of life. In contrast, if the tumor progresses to muscle-invasive bladder cancer,
radical cystectomy with urinary diversion is required, and patients need to carry a
stoma bag for life, which significantly affects their quality of life. Early
detection and early treatment can significantly improve the prognosis of bladder
cancer patients. At present, cystoscopy under ordinary white light (WLC) is the main
diagnostic method to check early bladder tumor and the presence of recurrence, and
it is widely used in clinical practice, but its accuracy still needs to be improved.
Therefore, in order to further improve the sensitivity and accuracy of cystoscopy,
we need some optical imaging techniques as an adjunct to WLC to improve the
visualization of tumors by contrast enhancement.
2. Narrow-band Imaging (NBI)： NBI is a diagnostic endoscopic illumination technology
developed by Olympus corporation and integrated into the camera of the cystoscope.
The NBI device filters out the red spectrum from white light, allowing the blue and
green spectra to be absorbed by hemoglobin. The different penetration of the two
spectra within the bladder mucosa enhances the contrast between vascular tissue and
normal bladder mucosa, improving the visualization of tumor neovascularization. The
shorter wavelength blue light (415 nm) band enters the superficial layer of the
mucosa, making the superficial capillaries brownish-black, and the longer wavelength
green light (540 nm) band enters the deeper layer of the mucosa, making the
submucosal vessels green. Thus, papillary tumors exhibit brownish-green lesions due
to the enhancement of submucosal capillaries and dark brown lesions due to the
enhancement of the dense superficial vascular system.
3. NBI classification criteria for different tumors： Currently, NBI classification
criteria have been established for both laryngeal tumors and intestinal tumors.
Clinical practice has confirmed that the sensitivity and specificity of NBI in the
diagnosis of laryngeal mucosal lesions are higher than those of WLC. researchers at
the Cancer Hospital of the Chinese Academy of Medical Sciences have classified
laryngeal lesions into 5 categories from precancerous to cancerous lesions and
confirmed through clinical validation that the classification criteria can help
identify precancerous lesions and tumors in the larynx at an early stage. The
Japanese NBI expert group also proposed a general NBI classification for colorectal
tumors in 2014, which classified colorectal lesions into polyps, low-grade
intramucosal neoplasia, high-grade intramucosal neoplasia/ superficial mucosal
invasive carcinoma, and deep mucosal invasive carcinoma according to their different
morphological characteristics under NBI. Although the NBI technique has been
clinically applied for more than 20 years, there is no uniform classification
standard for the manifestation of different bladder tumors under the NBI pattern,
and the microscopic diagnosis mostly relies on the clinician's experience, with the
possibility of misdiagnosis and missed diagnosis.
4. Purpose of the study： This study plans to develop the NBI classification criteria
for bladder lesions by summarizing and analyzing the morphological characteristics
of different bladder lesions in the NBI pattern, using the pathological findings as
a diagnostic basis, and assessing their sensitivity and specificity in order to
guide clinical work for a more standardized and accurate diagnosis of bladder tumors
and early recurrence, thus improving patient prognosis.
5. Research content： This is a prospective multicenter study, which includes all
patients who need to undergo cystoscopy and take biopsies in our center and
collaborating units, records the characteristics of performance under ordinary white
light and NBI in different parts of the bladder during cystoscopy, analyzes the
characteristics of NBI corresponding to different histopathology as the diagnostic
criteria, establishes the diagnostic classification standard of bladder tumor NBI,
and then verifies the reliability of this classification standard through clinical
validation. There are two key issues to be addressed in this project: (1) to clarify
the characteristics of different bladder lesions under NBI and establish a bladder
tumor NBI diagnostic classification system based on the pathological results; (2) to
clinically validate the accuracy of the classification criteria.
6. Cystoscopy method： The patient was placed in a lithotomy position, and the surgical
area was disinfected with iodophor and covered with towels, and the urethral mucosal
surface was anesthetized with 2% lidocaine gel. The morphological characteristics of
the mucosa and blood vessels under the microscope were recorded, and tissue biopsy
was performed in the suspected lesion area, and the biopsy tissue was stored in 10%
formalin solution for pathological examination. All operations were performed by
urologists of equal seniority who had undergone systematic training.
7. Sample size and establishment of classification method： Starting from January 1,
2021, cases were enrolled in our center and collaborating institutions
simultaneously according to the inclusion and exclusion criteria. Because the
different characteristics of mucosa and submucosal vessels of different nature of
tumors in the NBI pattern were easier to distinguish, the proposed sample size was
included in combination with the sample size included in the existing classification
criteria of colorectal tumors and laryngeal tumors (n=139, 104) as follows: 100
cases in the no lesion group, 200 cases in the benign lesion group, and 200 cases in
the malignant lesion group, and cystoscopy was performed according to the above
method.
For patients who did not require surgical treatment, the histopathological results
of biopsy were used as the diagnostic criteria; for patients whose biopsy pathology
suggested malignant bladder tumors and required TURBT or total cystectomy, the
postoperative pathological results were used as the diagnostic criteria. According
to the pathological results, all patients were divided into three groups: no lesion
group, benign lesion group, and malignant lesion group. All pathological results
were reported and reviewed by the hospital pathology center. The International
Society of Urological Pathology (ISUP) classification standard was used for
pathological classification, the WHO 2004 bladder cancer grading system was used for
histological grading, and the Union International Control Cancer (UICC) 2017 TNM
staging system was used for bladder cancer staging.
8. Blind design： The cystoscopy operation was performed by four urologists at each
center who were trained and dedicated to the operation, separate from the primary
clinician; neither the subject nor the investigator knew the patient number
information before complete subject screening and enrollment, and the cystoscopy
operator did not know the primary history information and relied only on the
microscopic presentation to give the initial diagnosis; blinded data review was
used.
9. Establishment of NBI diagnostic classification system for bladder tumors： Using the
pathological results as the "gold standard", the patients were divided into no
lesion group, benign lesion group and malignant lesion group, and analyzed the
morphological characteristics of normal mucosa, benign and malignant lesions, focal
mucosa and submucosal vessels, respectively, against the cystoscopic WLC and NBI
microscopic manifestations, to summarize and establish the diagnostic classification
system of bladder tumor NBI.
10. Clinical validation of the accuracy of the NBI diagnostic classification criteria
for bladder tumors： Sample size calculation: There is no diagnostic classification
standard for bladder tumor NBI, referring to the classification standard for
colorectal tumor NBI, the diagnostic sensitivity of its lesionless group, benign
lesion group and malignant lesion group are 75%, 91%, 35%, the specificity is 96%,
70%, 100%, also the tolerance error are 0.1, requiring one-sided test, α is 0.025,
the certainty is 80%. In this phase, it is proposed to initially include a total of
564 patients in accordance with this sample size, according to the inclusion and
exclusion criteria, prospectively, combined with the loss of follow-up rate (20%) in
each group, according to which the 3 groups need to include at least 211, 127, and
226 study subjects, respectively. After the completion of the first part of the
trial, the sample size can be corrected according to the established diagnostic
classification criteria for NBI, after the initial estimation of its sensitivity and
specificity.
The patients enrolled in the study were analyzed for cystoscopic NBI manifestations and
given a preliminary diagnosis according to the diagnostic classification of bladder tumor
NBI, also using tissue biopsy or surgical pathology as the "gold standard", and the
accuracy of this classification was calculated.
Main evaluation indexes: Sensitivity, Specificity, Area under the ROC curve. Secondary
evaluation metrics: Positive Predictive Value (PPV), Negative Predictive Value (NPV),
Positive Likelihood Ratio (PLR), Negative Likelihood Ratio (NLR), Accuracy Likelihood
Ratio (NLR), Accuracy, and Jouden Index.
Criteria for eligibility:
Study pop:
The subject population of this study was patients who required cystoscopy for definitive
diagnosis due to hematuria or bladder occupancy; or patients who were routinely reviewed
by cystoscopy after elective urinary bladder tumor resection (TURBT). They are all
patients who come to our hospital for examination or re-examination.
Sampling method:
Non-Probability Sample
Criteria:
Inclusion Criteria:
- Age between 18 and 75 years old.
- Patients who require cystoscopy for definitive diagnosis due to hematuria or bladder
occupancy; or patients who are routinely reviewed by cystoscopy after
electrodesiccation of urinary bladder tumor (TURBT).
- Subjects were able to understand the study content and sign the informed consent
form, and were able to actively cooperate and follow the study procedures.
Exclusion Criteria:
- People with coagulation disorders.
- Combined with acute urinary tract infection or postoperative infusion of BCG
vaccine.
- Urethral stricture or bladder volume too small to perform cystoscopy.
- Severe cardiopulmonary dysfunction who cannot tolerate local anesthesia surgery.
- Women who are menstruating or more than 3 months pregnant.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
Accepts Healthy Volunteers
Locations:
Facility:
Name:
Qilu Hospital of Shandong University (Qingdao)
Address:
City:
Qingdao
Zip:
266000
Country:
China
Status:
Recruiting
Contact:
Last name:
Jun Chen, PhD
Phone:
+8618560084873
Email:
chenjunxinxiang@163.com
Start date:
January 1, 2021
Completion date:
December 2024
Lead sponsor:
Agency:
Qilu Hospital of Shandong University (Qingdao)
Agency class:
Other
Collaborator:
Agency:
Qilu Hospital of Shandong University
Agency class:
Other
Collaborator:
Agency:
The Second Hospital of Shandong University
Agency class:
Other
Collaborator:
Agency:
Shandong Provincial Hospital
Agency class:
Other
Collaborator:
Agency:
Yantai Yuhuangding Hospital
Agency class:
Other
Collaborator:
Agency:
Qianfoshan Hospital
Agency class:
Other
Source:
Qilu Hospital of Shandong University (Qingdao)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05611762
