Editor's Note: Non-muscle-invasive bladder cancer (NMIBC) accounts for over 70% of all bladder cancer cases. For NMIBC patients, the primary treatment goals are to eliminate tumor cells, prevent recurrence and progression, while preserving bladder function and quality of life as much as possible. From August 8-11, 2024, the Annual Meeting of the Urological Surgeon Branch of the Chinese Medical Doctor Association (CUDA) was held in Xi'an. Following the event, Urology Frontier invited Dr. Hailong Hu from The Second Hospital of Tianjin Medical University to share insights on the unmet clinical needs of NMIBC patients in China, recent advances in novel treatment strategies, and future development directions.
Urology Frontier: What are the unmet clinical needs of NMIBC patients in China today?
Dr. Hailong Hu: The latest 2022 China Cancer Statistics report released by the National Cancer Center shows that the incidence rate of male bladder cancer is 5.7/100,000, making it the second most common urogenital tumor in China. Among these cases, NMIBC accounts for over 70%, requiring standardized diagnosis and treatment by clinical doctors.
For NMIBC patients, both urologists and general surgeons at grassroots hospitals can perform minimally invasive surgery (i.e., transurethral resection of the bladder tumor, TURBT), but this process requires attention to various details, including preoperative diagnosis, intraoperative pathology acquisition, and precise postoperative diagnosis. Any negligence could lead to unclear diagnosis or non-standardized treatment. Currently, NMIBC patients are classified into risk groups (low, intermediate, high, and very high risk), with corresponding treatment strategies tailored to each group.
In terms of treatment, China has also been exploring various strategies for NMIBC, covering a wide range of patient types, including those unresponsive to BCG therapy, patients who have not received BCG, and some intermediate-risk NMIBC patients. In the future, many new domestic drugs may be launched in China, further meeting the needs of NMIBC patients.
In terms of diagnosis, we can enhance the diagnostic performance for the Chinese population using blue-light cystoscopy and further improve diagnostic accuracy with new equipment and techniques set to be launched in 2024. Additionally, urine testing plays a vital role in the screening and diagnosis of bladder cancer. Routine urine tests can detect abnormalities through Pap staining or Reggio staining, but these methods have low sensitivity. Diagnostic techniques such as low-depth sequencing of urine, methylation testing, and analysis of urinary chromosomal instability, combined with artificial intelligence (AI), can improve the performance of non-invasive testing for NMIBC. In summary, from diagnosis to treatment, there are still many issues that need to be addressed for NMIBC patients.
Urology Frontier: New intravesical drug delivery systems like TAR-200 and TAR-210 have emerged for NMIBC patients unresponsive to BCG. What value do these strategies offer for patients who wish to preserve their bladder?
Dr. Hailong Hu: The application of intravesical slow-release devices represents an innovative clinical treatment strategy. Previously, bladder instillation therapy was commonly used, where chemotherapy drugs were introduced into the bladder via a catheter to destroy residual tumor cells and reduce tumor recurrence. However, this approach limited the duration of contact between the chemotherapy drugs and the bladder mucosa, making it difficult to achieve high concentrations of drug efficacy. Researchers developed these slow-release devices to control tumor progression by steadily releasing the drug. Studies have shown that the complete response (CR) rate of bladder instillation is below 30%, but with the use of slow-release devices, CR rates for drugs like gemcitabine can exceed 70%. Furthermore, for drugs targeting FGFR2/3 mutations like erdafitinib, the CR rate can be increased to over 90%, given that most luminal-type NMIBC patients harbor FGFR2/3 mutations.
In addition, other studies are exploring the application of these slow-release systems in the field of upper tract urothelial carcinoma (UTUC). Previously, UTUC treatment required total surgical resection to achieve tumor control, but now, with the potential use of slow-release devices, there may be an opportunity to preserve the kidney. We eagerly anticipate the future application of these slow-release treatment strategies to achieve better tumor control outcomes while preserving organs.
Urology Frontier: Recent conferences have highlighted studies on new ADC therapies for NMIBC. How should treatment strategies be selected to provide greater benefits for patients?
Dr. Hailong Hu: Antibody-drug conjugates (ADCs) can precisely deliver chemotherapy drugs to tumor sites with high expression of specific targets, effectively killing tumor cells while reducing drug concentration in surrounding tissues, thereby minimizing side effects. Currently, ADCs are widely used as second-line or first-line treatments in advanced bladder cancer. At this year’s ASCO, promising results were reported for neoadjuvant treatment with immunotherapy combined with enfortumab vedotin in muscle-invasive bladder cancer (MIBC).
For NMIBC, The Second Hospital of Tianjin Medical University conducted a nationwide multi-center analysis, revealing that over 50% of NMIBC patients were HER2 IHC3+, providing a pathological basis for ADC treatment of NMIBC. Could ADC combined with immunotherapy also benefit NMIBC patients unresponsive to BCG? Our hospital’s study, which included NMIBC patients with high tumor burden and HER2 IHC 1+ or higher, explored bladder-sparing treatment with ADC combined with immunotherapy. This investigator-initiated single-center study has shown promising results, indicating the need for future multi-center prospective studies to further analyze efficacy.
For NMIBC patients, systemic treatment has shown good tumor control effects. However, NMIBC’s overall tumor burden is relatively low, with no detectable circulating tumor cells in the blood system, making it necessary to further study the proportion of systemically administered drugs that reach the target organ, the bladder. Since NMIBC is primarily concentrated in the bladder lumen, the possibility of using direct instillation of relevant drugs is also a current clinical research focus. Professor Huang Jian and Professor Lin Tianxin from Sun Yat-sen Memorial Hospital, Sun Yat-sen University, are leading nationwide clinical trials on bladder instillation of ADCs, and we look forward to the publication of these results to bring more treatment options to clinical practice.
Urology Frontier: What directions do you think are worth exploring further in the future for NMIBC?
Dr. Hailong Hu: NMIBC accounts for over 70% of all bladder cancer cases, so managing the entire process from diagnosis to treatment needs optimization. With the advent of the AI era, one of the future directions is how to apply AI to improve work efficiency, screen for high-benefit populations, and enhance patient prognosis. For example, cystoscopy typically requires experienced doctors to accurately identify potential tumors, with more experienced doctors achieving higher consistency with pathological diagnoses. AI models, through extensive learning, can directly assist grassroots doctors in diagnosis and treatment, thereby improving survival for grassroots patients. This technological downshift strategy can also use AI for non-invasive detection of exfoliated cells and assist in the diagnosis of bladder cancer, compensating for the lack of exfoliated cell cytology testing capabilities in some hospitals. Additionally, the PLA General Hospital has conducted clinical research on China’s domestically developed surgical robots. In the future, surgeries may be performed directly by robots, with doctors managing remotely. These are all potential future directions for development.
Dr. Hailong Hu
Deputy Director of the Urology Ward A, Second Hospital of Tianjin Medical University Ph.D. Supervisor, Tianjin Medical University Visiting Scholar, Mayo Clinic and University of Southern California Deputy Director, Gene Engineering Laboratory, Tianjin Institute of Urology Vice Chairman, Youth Committee, Urology Professional Committee, Chinese Society of Integrated Traditional Chinese and Western Medicine Member, Robotic Surgery Group, Urology Professional Committee, Chinese Medical Association Vice Chairman, Urology Professional Committee, Tianjin Society of Integrated Traditional Chinese and Western Medicine Research Focus: Individualized and Minimally Invasive Treatment of Bladder Cancer
