Transurethral resection of bladder tumor (TURBT) followed by intravesical therapy remains the most effective strategy for the management of non-muscle-invasive bladder cancer worldwide. TURBT has two purposes: to remove all visible tumors and to obtain tumor specimens for histopathological analysis. However, the detection of flat and small malignant lesions under white-light cystoscopy is extremely challenging, and residual lesions are still the main reason for the high recurrence rate of bladder cancer. We hypothesized that visual enhancement of malignant lesions using targeted optical molecular imaging could potentially highlight residual tumors in the bladder during surgery, and near-infrared photoimmunotherapy (NIR-PIT) could kill exfoliated cancer cells and residual tumors. A mouse model of complete or partial bladder tumor resection was established under the guidance of optical molecular imaging mediated by indocyanine green and anti-CD47-Alexa Fluor 790, respectively. Once the tumor recurred, mouse model received repeated CD47-targeted NIR-PIT. After complete resection, there was no tumor recurrence. Furthermore, the growth rate of recurrent tumor decreased significantly after repeated NIR-PIT. Therefore, CD47-targeted optical molecular imaging can potentially assist urologists to detect and remove all tumors, and repeated NIR-PIT shows the potential to reduce tumor recurrence rates and inhibit the growth of recurrent tumor.

Due to the high recurrence and progression rate of non-muscle invasive bladder cancer after transurethral resection of bladder tumor, some new optical imaging technologies have arisen as auxiliary imaging modes for white light cystoscopy to improve the detection rate of small or occult tumor lesions, such as photodynamic diagnosis, narrow-band imaging, and molecular imaging. White light cystoscopy is inadequate and imperfect for bladder cancer detection, and thus residual tumors or coexisting flat malignant lesions, especially carcinoma in situ, would be ignored during conventional resection. The bladder, a hollow organ with high compliance, provides an ideal closed operation darkroom for endoscopic molecular imaging free from interference of external light sources. Also, intravesical instillation of a molecular fluorescent tracer is simple and convenient before surgery through the urethra. Molecular fluorescent tracer has high sensitivity and specificity to tumor cells, and its mediated molecular imaging allows small or occult tumor lesion detection while minimizing false-positive results. Meanwhile, endoscopic molecular imaging provides a real-time and dynamic image during surgery, which helps urologists to perform high-quality and complete tumor resection through accurate judgment of tumor boundaries and depth of invasion. Photoimmunotherapy is a novel molecular targeted therapeutic pattern of photodynamic therapy that kills malignant cells selectively and minimizes the cytotoxicity to normal tissues. The combination of endoscopic molecular imaging and photoimmunotherapy used in initial treatment may avoid the need of repeat transurethral resection in strictly selected patients and improve oncological outcomes such as recurrence-free survival and overall survival after operation.

Objective: To evaluate the safety and efficacy of overnight continuous saline bladder irrigation (CSBI) for patients who have received thulium laser en bloc resection of bladder tumor (TmLRBT) combined with immediate intravesical chemotherapy previously.Methods: From October 2014 to June 2018, 235 patients with newly diagnosed non-muscle invasive bladder cancer (NMIBC) were included in this retrospective study. All patients received intravesical instillation of pirarubicin immediately after TmLRBT. The patients were divided into two groups according to the duration of postoperative bladder irrigation with normal saline. After immediate intravesical chemotherapy, patients in group 1 received overnight CSBI, while patients in group 2 did not receive overnight CSBI. Data on the time of initial tumor recurrence, recurrence-free survival (RFS) and progression-free survival (PFS) rates, and perioperative complications were collected and analyzed.Results: Of 235 included patients (129 in group 1 and 106 in group 2), the median follow-up periods were 42 and 38 months, respectively. There were no significant differences in patients’ baseline characteristics between the two groups. The RFS rates of patients in group 1 were 90.7, 82.7, and 76.8% at the end of the first, third, and fifth years, while the corresponding RFS rates of patients in group 2 were 87.7, 78.9, and 73.3%, respectively. Four patients in group 1 and five patients in group 2 experienced tumor progression. No significant differences between the two groups were observed in the time of initial tumor recurrence, RFS, and PFS rates. Only Grade I complications occurred in the two groups, and no significant difference was reached between the two groups.Conclusions: For patients with NMIBC who have previously received TmLRBT combined with immediate intravesical chemotherapy, overnight CSBI may not improve oncological outcomes and reduce perioperative complications.

Although transurethral resection of bladder tumor is the golden standard for the treatment of non-muscle invasive bladder cancer, this surgical procedure still has some serious drawbacks. For example, piecemeal resection of tumor tissue results in exfoliated tumor cells dissemination and implantation, and fragmented tumor specimens make it difficult for pathologists to accurately assess the pathological stage and histologic grade. En bloc tumor resection follows the basic principle of oncological surgery and provides an intact tumor specimen containing detrusor muscle for pathologists to make accurate histopathological assessment. However, there is no robust clinical evidence that en bloc tumor resection is superior to conventional resection in terms of oncological outcomes. Considering the high recurrence rate, small or occult tumor lesions may be overlooked and incomplete tumor resection may occur during white light cystoscopy-assisted transurethral resection. Molecular fluorescent tracers have the ability to bind tumor cells with high sensitivity and specificity. Optical molecular imaging mediated by it can detect small or occult malignant lesions while minimizing the occurrence of false-positive results. Meanwhile, optical molecular imaging can provide dynamic and real-time image guidance in the surgical procedure, which helps urologists to accurately determine the boundary and depth of tumor invasion, so as to perform complete and high-quality transurethral tumor resection. Integrating the advantages of these two technologies, optical molecular imaging-assisted en bloc tumor resection shows the potential to improve the positive detection rate of small or occult tumor lesions and the quality of transurethral resection, resulting in high recurrence-free and progression-free survival rates.