Confocal Laser Endomicroscopy During TransUrethral Resection for Improving BC Diagnosis and Treatment

NCT ID: NCT05273593

Last Updated: 2022-03-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-06
• Study Completion Date: 2021-11-12

Brief Summary

A prospective monocenter diagnostic accuracy study of Confocal Laser Endomicroscopy (CLE) for Bladder Cancer(BC) to assess two primary objectives:

1. The diagnostic accuracy of flexible probe-based confocal laser endomicroscopy (CLE) compared to histopathology of the resection specimen.

2. The diagnostic accuracy of CLE-based assessment of the surgical radicality of the resection bed (radical vs irradical) in comparison with histopathology of a biopsy of the resection bed.

All patients with a papillary bladder tumor on cystoscopy will be included in this trial.

Detailed Description

Rationale:

Initial evaluation of gross hematuria consists of White Light Cystoscopy (WLC). Urine cytology combined with contrast imaging of the upper urothelial tract is performed when a bladder tumor is seen. Follow up of non-muscle invasive bladder carcinoma (NMIBC) after initial treatment consists of similar steps. When a suspected lesion is visualized, a transurethral resection of the bladder tumor (TURBT) is performed for therapeutic and diagnostic purposes. TURBT is considered to be the gold standard for diagnosis of urothelial carcinoma of the bladder (UCB). High recurrence rates of UCB after TURBT are reported, leading to repetitive surgery and high costs. In certain cases of high grade UCB a second look TURBT has proven to be beneficial after primary resection to ensure radical resection. Furthermore, recent research suggests that active surveillance for low-grade bladder tumors is safe. Confocal laser endomicroscopy (CLE), a high resolution optical imaging technique that can be used in combination with endo-urological procedures, seems promising to improve diagnosis of urothelial cancer, possibly without the need for immediate transurethral resection to obtain histological confirmation. CLE characteristics of UCB have been determined and validated using rigid probes, which are incompatible with flexible cystoscopes used for outpatient cystoscopies. With the present study, we aim to assess the diagnostic value of flexible probe based CLE for diagnosis and grading of UCB. Furthermore to possibly prevent second look TURBT in the future,an assessment of CLE features of the resection bed using a rigid CLE-probe will be performed.

Objective:

Primary objectives:

This study is two-fold and, therefore, has two primary objectives:

1. Investigating the diagnostic accuracy of CLE (Cystoflex™F probe) during flexible cystoscopy for diagnosis and grading of urothelial carcinoma of the bladder.

2. To investigate the diagnostic potential of CLE (Cystoflex™ UHD-R probe) for the assessment of the surgical radicality after transurethral resection of a bladder tumor (after TURBT)

Secondary objective:

• To construct a convolutional neural network for computer aided assessment of CLE images for diagnosis and grading of UCB.

Study design:

This is a prospective monocenter, observational diagnostic accuracy study. Diagnostic accuracy study to compare the CLE-based diagnosis with the histopathologic findings.

Study population: All patients >18 years old with a papillary bladder tumor who are planned for TURBT are eligible for this study. We will include 60 patients in this pilot study.

Intervention: At the operation theatre, before performing a TURBT for the standard clinical care, we introduce a flexible cystoscope to map the bladder, then we record CLE images of the index lesion using the Cystoflex™F. Subsequently, we replace the flexible scope by the (rigid) resectoscope. We acquire additional images with the Cystoflex™ UHD-R rigid probe. We perform the TURBT. After completion of the TURBT, we introduce the Cystoflex™ UHD-R probe again for imaging of the resection bed. At a later stage correlation with a standard biopsy of the resection bed will be performed.

For CLE imaging, a fluorescent contrast agent (fluorescein) will be used intravesically and intravenously, respectively, to temporarily stain the extracellular matrix of the urothelium. We will introduce fluorescein for intravesical use through a bladder catheter and rinse the fluorescein out of the bladder after an indwelling time of 5-10 minutes. Before CLE measurement of the resection bed we will administer fluorescein intravenously.

Main study parameters/endpoints:

1. Overall accuracy, sensitivity and specificity of flexible probe CLE-based diagnosis (benign vs malignant) and grading (low-grade versus high-grade) in comparison with the histopathology of the resection specimen.

2. Overall accuracy, sensitivity and specificity of CLE-based assessment of the surgical radicality of the resection bed (radical versus irradical) in comparison with the histopathology of the biopsy of the resection bed.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Participants will not benefit directly from this study. We hypothesize, however, that the results of this study will contribute to improvements in the diagnostic and surgical procedure for UCB. Outpatient-based cystoscopy with the potential diagnostic certainty of CLE-based grade assessment may enable active surveillance in low-risk UCB, and thus may even lead to a reduction in surgical procedures. We will introduce a CLE probe before TURBT via the working channel of the flexible cystoscope and hold it in direct contact with the bladder tumor to obtain CLE images. Before image acquisition of the bladder tumor we administer fluorescein intravesical, which is a fluorescent dye, used regularly intravenously in ophthalmatology. Before image acquisition of the resection bed we administer fluorescein intravenously. In patients not known with an allergy to this dye, this is a safe procedure. Patients with a known allergic reaction to fluorescein cannot participate in this study. Patients will be exposed to approximately 20 minutes of extra surgery time and the introduction of a flexible cystoscope compared to regular TURBT. As a result there is little burden to study participation for the patients. Adverse events are not expected based on previous experiences. The hospital's internal protocol for standard clinical care and histopathologic evaluation are not going to be affected by the study protocol.

Conditions

Bladder Cancer; CLE

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Interventions

Confocal Laser Endomicroscopy (CLE)

Administration of fluorescein, intravesically and intravenously. CLE measurements with flexible and rigid probe of papillary bladder tumour and rigid probe-measurement of resection bed.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Display a papillary bladder tumor on cystoscopy.
• >18 years of age.
• Has given written informed consent.

Exclusion Criteria

• Patients with a known allergy to fluorescein.
• Pregnancy or lactating women.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role: lead

Responsible Party

Prof.dr. H.P. Beerlage

Head of Department of Urology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

J. R. Oddens, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Staff member of Urology Department

Locations

Academic Medical Center

Amsterdam, North Holland, Netherlands

Countries

Netherlands

Other Identifiers

NL71360.018.19

Identifier Type: -

Identifier Source: org_study_id