Confocal Laser Endomicroscopy before transurethral resection for optimizing Bladder Cancer diagnosis and treatment.

Initial evaluation of gross hematuria consists of WLC. Urine cytology combined
with contrast imaging of the upper urothelial tract is performed when a bladder
tumour is seen. Follow up of 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 tumours 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.

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 tumour (after TURBT)
Secondary objective:
- To validate a previously constructed convolutional neural network for
computer aided assessment of CLE images for diagnosis and grading of UCB.

This is a prospective, monocenter pilot study investigating the diagnostic
accuracy of flexible pCLE. Furthermore it will assess the feasibility of CLE
for assessment of the resection bed. Patients planned for TURBT will be asked
to participate.

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
tumour to obtain CLE images. Before image acquisition of the bladder tumour 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 at risk for a
demonstrated allergic reaction 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.