This is a prospective, multicenter, randomized controlled superiority study designed to evaluate whether the addition of pelvic lymph node dissection improves bladder-intact event-free survival in patients with cT2-3N0M0 bladder urothelial carcinoma receiving bladder-sparing treatment. Eligible patients with HER2 expression of IHC 2+ or higher who decline radical cystectomy will be randomized 1:1 to receive maximal transurethral resection of bladder tumor followed by disitamab vedotin plus toripalimab with or without standardized pelvic lymph node dissection. The primary endpoint is the 2-year bladder-intact event-free survival rate. Secondary endpoints include clinical complete response, partial response, disease progression, overall survival, quality of life, safety, treatment cost, and exploratory biomarker analyses.
Male or female participants aged 18 years or older.
Histologically confirmed bladder urothelial carcinoma.
Clinical stage cT2-3N0M0 according to the AJCC 8th edition TNM staging system.
HER2 expression of IHC 2+ or higher.
Known allergy or hypersensitivity to disitamab vedotin, toripalimab, their excipients, or other monoclonal antibodies.
Prior radiotherapy for bladder cancer.
Prior anticancer treatment that may affect efficacy assessment, as defined in the study protocol.
Pregnant or breastfeeding women.
Parallel
Disitamab Vedotin (RC48)
DrugDisitamab vedotin will be administered in combination with toripalimab according to the study protocol.
Toripalimab
DrugToripalimab will be administered in combination with disitamab vedotin according to the study protocol.
Transurethral Resection of Bladder Tumor
Procedure/SurgeryMaximal transurethral resection of bladder tumor will be performed as part of the bladder-sparing treatment strategy.
Pelvic Lymph Node Dissection
Procedure/SurgeryStandardized pelvic lymph node dissection will be performed in participants assigned to the PLND arm.
2-year Bladder-intact Event-free Survival Rate
The proportion of participants who remain alive with an intact bladder and without muscle-invasive bladder cancer recurrence, regional lymph node recurrence, distant metastasis, radical cystectomy, or bladder cancer-related death at 24 months after randomization.
Clinical Complete Response Rate
The proportion of participants who achieve clinical complete response, defined as no visible tumor on imaging, no evidence of malignancy on cystoscopy or TURBT/biopsy when clinically indicated, and negative urine cytology. For participants undergoing pelvic lymph node dissection, no lymph node metastasis is required.
Partial Response Rate
The proportion of participants with non-muscle-invasive disease, including Ta, T1, or carcinoma in situ, confirmed by urine cytology or pathological biopsy, with no evidence of locally advanced or metastatic disease on imaging.
Disease Progression Rate
The proportion of participants with disease progression, defined as muscle-invasive bladder cancer confirmed by pathological biopsy, locally advanced disease, regional lymph node recurrence, distant metastasis, or bladder cancer-related death.
Overall Survival
Overall survival is defined as the time from randomization to death from any cause.
2-Year Bladder-Intact Event-Free Survival Rate by Baseline HER2 IHC Category
Pretreatment tumor HER2 expression will be assessed by immunohistochemistry and categorized as IHC 2+ or IHC 3+. The percentage of participants meeting the 2-year bladder-intact event-free survival definition will be estimated separately for each HER2 IHC category. Bladder-intact event-free survival is defined as being alive with an intact bladder and without muscle-invasive bladder cancer recurrence, regional lymph node recurrence, distant metastasis, radical cystectomy, or bladder cancer-related death. The unit of measure is percentage of participants.
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Tianjin Medical University Second Hospital
Lead sponsor
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Collaborator
The First Affiliated Hospital with Nanjing Medical University
Collaborator
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