The standard in diagnostics of transitional-cell carcinoma (TCC) of the bladder is the visual approach including the need for biopsies or transurethral resection of the bladder (TURB). Although most bladder tumors can be identified with white light cystoscopy, it has been shown that, especially in high-grade tumors, areas of carcinoma in situ (CIS) are missed. ¹ Optimizing TURB by improving visualization of the tumors is highly desirable. New techniques such as the use of photodynamic agents (e.g., Hexvix) and narrow band imaging (NBI) have been studied. ² It should be underlined that the Clinical Research Office of the Endourological Society (CROES) is currently running a randomized controlled study on NBI. ³

Recently, a new development in imaging has been introduced by Karl Storz and is now ready for clinical evaluation. With the Storz Professional Image Enhancement System (SPIES), no endoscopic filter is needed to enhance the image to gain more clarity. SPIES is based on a new software platform, which uses the different light wavelengths to produce images with different contrast specifications. It offers a technique that could be useful in bladder cancer treatment, because clearer images are likely to result in reducing the numbers of tumors that are missed by the gold standard White Light Imaging (WLI). In addition, once the tumor is detected, SPIES images may help find the demarcation between tumor and healthy tissue, resulting in more complete resection of the tumor(s). The recurrence rate is expected to be decreased with the use of SPIES by obtaining a more complete resection, meaning the patient will need less invasive diagnostic and surgical visits.

For these reasons, CROES is going to conduct the SPIES study. This study is a multicenter randomized controlled trial in which the recurrence rates of bladder carcinoma between SPIES assisted and WLI assisted TURB are compared. Eligible patients will be randomized, in a ratio of 1:1, and randomization is stratified by tumor multiplicity (single or multiple), tumor status (primary or recurrent), and macroscopic findings (papillary or flat, where CIS is scored as flat lesion). Patients randomized into the experimental arm (Arm A) will undergo SPIES and WLI assisted TURB, whereas the patients in the control arm (Arm B) will undergo WLI only assisted TURB. WLI is chosen as the control, because it is considered the gold standard for detecting bladder tumors. Short- and long-term follow-up will be recorded to evaluate the health gains for patients over a longer period. Perioperative (30 days) complications will be compared between the two treatment arms to evaluate the safety of SPIES.

This study will be conducted in compliance with the current revision of the Declaration of Helsinki, ICH guidelines for Good Clinical Practice, and applicable local regulatory requirements. Each participating center must submit this protocol to their local Medical Ethics Committee (MEC). Data from all participating centers will be collected through electronic Case Report Forms, with use of an online Data Management System, which is located and maintained at the CROES office. Members of the CROES office will perform all analyses. Each center willing to participate should have enough experience and be familiar with SPIES. A center is considered to have enough experience when a minimum of 10 to 20 procedures have already been performed with SPIES before including patients in this study.

Primary study objective

1. To compare the recurrence rate of tumor at 12 months after SPIES assisted TURB (Arm A) with White Light Imaging only assisted TURB (Arm B) in patients with primary or recurrent nonmuscle-invasive urothelial bladder cancer (NMIBC T_a/T₁/CIS). The study is designed to be powered at 80% to detect an estimated reduced recurrence rate of 10% at 1 year between the two groups of treated patients. A subgroup analysis will be performed for patients presenting with only primary tumors.

Secondary objectives

1. To assess the recurrence rate of tumor at short- and long-term follow-up (3 months and 3 years) after SPIES or WLI assisted TURB in patients with NMIBC.

2. To assess the perioperative morbidity (30 days) between SPIES and WLI assisted TURB by comparing the proportion of adverse events and using the Clavien-Dindo score.

The creation of a global network such as CROES facilitates and makes feasible the implementation of multicenter, relatively low-cost studies that have the ability to generate large samples rapidly. In addition, the objective of CROES is to promote high quality research on endourology/laparoscopy. Into this frame, CROES aims to conduct randomized controlled trials that are considered the reference standard for evaluating therapy alternatives and establishing standards of care in diagnostics and treatments. Therefore, the results of the SPIES project (both clinical and organizational) are awaited with great interest.