The urothelial carcinoma research team led by Professor Hailong Hu, Principal Investigator (PI) of the urothelial carcinoma subspecialty in the Department of Urology at the Second Hospital of Tianjin Medical University, has published the TRUCE-04 clinical study as an Original Investigation in JAMA Oncology, a leading international oncology journal with an impact factor of 23.9. The journal is part of the JAMA Network and is classified as a Chinese Academy of Sciences Q1 Top journal. The article is entitled “Disitamab Vedotin Plus Tislelizumab in Transurethrally Unresectable, ERBB2-Positive, Non-Muscle-Invasive Bladder Cancer.”As a progressive extension of the TRUCE series investigating organ-preserving treatment, the team previously completed the TRUCE-02 study, published in Clinical Cancer Research. That study provided preliminary evidence that immunotherapy combined with low-dose nab-paclitaxel could enable bladder preservation in a broad population of patients with very-high-risk non-muscle-invasive bladder cancer (VHR NMIBC) whose tumors were unresectable through a transurethral approach.
Building on these findings, the team focused on a more aggressive and treatment-resistant subgroup characterized by high ERBB2 expression. The TRUCE-04 study was the first to explore a treatment strategy combining an antibody-drug conjugate (ADC) with an immune checkpoint inhibitor in this population, with the aim of further improving bladder-preservation outcomes.
Unmet Clinical Needs in Very-High-Risk NMIBC
Among patients with VHR NMIBC, some have a high tumor burden and diffuse disease that cannot be completely removed through transurethral surgery. According to clinical practice guidelines, radical cystectomy is the standard treatment for these patients. However, the procedure is highly invasive, carries a substantial risk of complications, and can severely affect quality of life. Moreover, many older patients and those with multiple underlying medical conditions cannot tolerate surgery, while others strongly refuse complete bladder removal.
Traditional intravesical bacillus Calmette–Guérin (BCG) therapy has limited efficacy against large-volume or extensive lesions and is also associated with substantial drug-related toxicity and adverse reactions.
The TRUCE-02 study systematically explored immunotherapy in the broader population of patients with transurethrally unresectable VHR NMIBC. In clinical practice, approximately 90% of bladder cancers express ERBB2 at a level of at least 1+, while the proportion with high ERBB2 expression (≥2+) may reach 70%, according to the latest statistics from the Tianjin Urology Clinical Translational Research Collaboration Group.
For patients with ERBB2-positive disease, which is associated with more aggressive tumor behavior, established and effective bladder-preserving strategies remain lacking. Targeted clinical research is therefore urgently needed to address this unmet need.
TRUCE-04: Exploring ADC Plus Immunotherapy for Bladder Preservation
ADC-based combination immunotherapy has demonstrated strong antitumor activity in muscle-invasive and advanced urothelial carcinoma. However, its value in NMIBC—particularly in patients with transurethrally unresectable, very-high-risk disease—has remained uncertain because high-level clinical evidence is limited.
To address this gap, the research team conducted the Phase II TRUCE-04 clinical study, retaining the core inclusion and exclusion criteria and efficacy assessment framework established in TRUCE-02 while adding molecular screening for ERBB2 as a selection criterion.
Patients were enrolled between August 2022 and May 2024, and the median follow-up was 29.4 months. Interim findings were previously presented orally at the European Association of Urology (EAU) scientific meeting. The final results have now been published online in JAMA Oncology.
Key Findings: Promising Complete Response and Survival Outcomes
The TRUCE-04 results showed that, following treatment with disitamab vedotin plus tislelizumab, the complete response rate among high-risk lesions in the 26 evaluable patients was 73.1%.
Among patients who achieved a complete response, the 24-month sustained response rate was 83.5%. No patients developed muscle-invasive or metastatic bladder cancer during follow-up. The 24-month progression-free survival rate was 95.5%, and the overall survival rate was 96.2%.
The safety profile was also encouraging. Most adverse events were mild to moderate, and only 14.3% of participants experienced Grade 3–4 adverse events. No treatment-related deaths occurred, and only two patients discontinued treatment because of adverse events. These findings were consistent with the known adverse-event profiles of the two drugs.
Overall, this treatment strategy demonstrated a favorable safety profile, with manageable adverse effects, and may offer a safe and reliable bladder-preserving option for this difficult-to-treat patient population.
Research Team and Funding
Professor Hailong Hu served as the corresponding author. Associate Researcher Yunkai Qi was the first author. Doctoral students Kaipeng Jia, Shiwang Huang, and Zihan Xue, together with master’s student Jiazeng Zhao, were co-first authors. Dr. Chong Shen served as a co-corresponding author.
The study received funding from several sources, including the National Science and Technology Major Project for Major Chronic Diseases, the National Natural Science Foundation of China, the National Key Research and Development Program of China, a joint project supported by the Tianjin Natural Science Foundation, and the Tianjin Medical Key Discipline Construction Project.
About the Authors
Professor Hailong Hu
Associate Researcher Yunkai Qi
Dr. Chong Shen
