Study on Precise Resection of Non-Muscle Invasive Bladder Cancer Guided by Trop2-Targeted Near-Infrared Fluorescence Imaging Technology

1. Research Background Bladder cancer ranks the fifth most common human malignancy, with an incidence rate of 81.2 per 100,000 individuals. Approximately 70% of patients present with non-muscle invasive bladder cancer (NMIBC) at initial diagnosis, wherein tumors are superficial (carcinoma in situ) or confined to the mucosa (Ta) and submucosa (T1). Up to 90% of NMIBC cases are pathologically confirmed as urothelial neoplasms. Urothelial tumors exhibit heterogeneous morphological features, which may be solitary, multiple, flat or exophytic, and can arise anywhere on the urothelial lining of the bladder. Bladder cancer generally confers a favorable prognosis, especially when detected at early Ta or T1 stages.

Although white-light cystoscopy, recommended by cancer prevention guidelines, serves as a convenient and noninvasive modality for bladder cancer detection, up to 30% of tumors may be missed-particularly small satellite lesions and flat carcinoma in situ. This oversight contributes to a recurrence rate as high as 70%, and recurrent lesions may progress to invasive carcinoma, severely impairing patients' quality of life. Therefore, improving the detection performance of bladder cancer, especially for lesions frequently overlooked by conventional approaches, will optimize the prognosis of patients with NMIBC.

Novel imaging modalities have recently been developed to enhance tumor detection rates. Endoscopic techniques including narrow-band imaging and blue-light cystoscopy have been introduced to boost tumor identification and guide endoscopic resection. Nevertheless, these approaches are limited by high false-positive rates due to insufficient specificity. Microscopic imaging technologies, such as confocal laser endomicroscopy and optical coherence tomography, can visualize tissue microarchitecture and cellular morphology; however, their narrow field of view renders them unsuitable for full bladder survey.

Near-infrared (NIR) fluorescence imaging has emerged as a promising precision imaging technique widely adopted in precision surgery. Accurate intraoperative tumor recognition relies not only on the high signal-to-noise ratio of NIR imaging but also on specific enrichment of targeted fluorescent dyes at tumor sites. Researchers have developed a variety of fluorescent probes that actively target tumors at the molecular and cellular levels for surgical navigation. Most such strategies target mutated or overexpressed tumor-specific biomarkers in solid tumors, such as folate receptor α, epidermal growth factor receptor, and tumor-associated antigens (e.g., prostate-specific membrane antigen, carcinoembryonic antigen), or exploit enzymes overexpressed in tumor tissues, including cathepsins and matrix metalloproteinases.

Human trophoblast cell surface antigen 2 (Trop2), a single-pass transmembrane cell-surface glycoprotein, belongs to the tumor-associated calcium signal transducer (TACSTD) family. Trop2 is overexpressed in multiple solid malignancies including breast cancer and bladder urothelial carcinoma, and plays critical roles in cell self-renewal, proliferation and invasion. Encouragingly, sacituzumab govitecan (SG), an antibody-drug conjugate (ADC) targeting Trop2, has been approved by the U.S. Food and Drug Administration for the treatment of locally advanced or metastatic urothelial carcinoma, further validating Trop2 as a reliable therapeutic target for bladder urothelial carcinoma. Accordingly, construction of an NIR fluorescent probe targeting Trop2 is expected to enable precise intraoperative navigation for NMIBC and improve patient prognosis. 2. Research Objective Based on Trop2, a specific target of bladder urothelial carcinoma, this study employs a Trop2-targeted NIR fluorescent probe combined with a rapid intravesical incubation imaging system to investigate the safety profile of this imaging system and whether it can improve the intraoperative detection accuracy of NMIBC (to assist surgeons in localizing NMIBC lesions during surgery). 3. Study Procedures If you volunteer to participate in this study and sign the informed consent form, study investigators will conduct pre-enrollment screening. You will be enrolled only if you meet all eligibility criteria.