This study will evaluate whether adjuvant intravesical chemotherapy can be safely omitted under active surveillance after complete transurethral resection in selected patients with EAU intermediate-risk non-muscle-invasive bladder cancer.
Patients with intermediate-risk non-muscle-invasive bladder cancer are commonly treated with transurethral resection followed by adjuvant intravesical chemotherapy to reduce the risk of recurrence. However, not all patients may derive the same benefit from additional intravesical treatment. Some tumors may have a low-shedding phenotype, meaning that they show no detectable tumor-associated signals in urine despite the presence of visible bladder tumors.
In this study, preoperative urine-based liquid biopsy will be used to identify patients with a low-shedding profile. This profile is defined by negative results across urine cytology, NMP22, urinary DNA methylation, and urinary tumor DNA testing before transurethral resection.
Eligible patients with EAU intermediate-risk non-muscle-invasive bladder cancer, a negative preoperative urine-based liquid biopsy profile, and complete tumor resection will be randomly assigned to active surveillance or standard adjuvant intravesical chemotherapy. The study will compare recurrence-free survival between the two groups and assess whether active surveillance can avoid immediate intravesical chemotherapy without compromising oncologic safety. Secondary outcomes will include high-grade recurrence, disease progression, need for subsequent bladder cancer treatment, safety, patient-reported outcomes.
Age ≥18 years.
Histologically confirmed urothelial carcinoma of the urinary bladder, including tumors with divergent differentiation, provided that the urothelial carcinoma component accounts for >50% of the tumor
Non-muscle-invasive bladder cancer classified as intermediate-risk according to the 2021 European Association of Urology (EAU) NMIBC prognostic risk-group definition. Intermediate-risk disease is defined as NMIBC without concomitant carcinoma in situ that does not meet the criteria for the EAU low-, high-, or very-high-risk groups.
Complete transurethral resection of all visible bladder tumors performed within 6 weeks before randomization, with no macroscopically visible residual disease.
EAU low-risk, high-risk, or very-high-risk NMIBC.
Any current or previous concomitant carcinoma in situ associated with the qualifying tumor episode.
Muscle-invasive bladder cancer, locally advanced urothelial carcinoma, lymph-node involvement, or metastatic urothelial carcinoma.
Urothelial carcinoma involving the prostatic stroma or prostatic ducts, or carcinoma in situ of the prostatic urethra.
Parallel
Active Surveillance
Other interventionParticipants assigned to active surveillance will not receive adjuvant intravesical chemotherapy after complete transurethral resection of bladder tumor. They will undergo scheduled follow-up assessments, including cystoscopy, urine cytology, urine-based liquid biopsy testing, imaging when clinically indicated, and other evaluations according to the study protocol. Further diagnostic evaluation or treatment will be initiated if recurrence or progression is suspected or confirmed.
Adjuvant Intravesical Chemotherapy
DrugParticipants assigned to this intervention will receive one year of adjuvant intravesical chemotherapy after complete transurethral resection of bladder tumor. Gemcitabine is the preferred protocol-specified agent. Mitomycin C or epirubicin may be used as protocol-allowed alternatives when gemcitabine is unavailable, contraindicated, or not routinely used at the participating center. Treatment will include an induction course followed by maintenance intravesical instillations for up to 12 months.
Recurrence-free survival
Recurrence-free survival is defined as the time from randomization to the first histologically confirmed intravesical recurrence or death from any cause, whichever occurs first.
High-grade recurrence-free survival
High-grade recurrence-free survival is defined as the time from randomization to the first histologically confirmed high-grade intravesical recurrence or death from any cause, whichever occurs first.
Progression-free survival
Progression-free survival is defined as the time from randomization to the first occurrence of T1 high-grade disease, carcinoma in situ, muscle-invasive bladder cancer, upper tract urothelial carcinoma, nodal or distant metastasis, radical cystectomy, or death from any cause.
Overall Survival
Defined as the time from randomization to the date of death from any cause
European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire Core-30 items (EORTC-QLQ-C30) Scores
EORTC QLQ-C30 is a core 30-item questionnaire for evaluating the health-related quality of life (HRQoL) of participants participating in cancer clinical studies. It incorporates 5 functional scales (physical, role, cognitive, emotional, and social functioning), 3 symptom scales (fatigue, pain, and nausea or vomiting), and a global health status or HRQoL scale. Ratings for each item range from 1 (not at all) to 4 (very much). Higher scores indicated greater severity.
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