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.