Multicenter Clinical Trial on the Effectiveness and Safety of Instillation of BCG and Alternative BCG Protocols for Intermediate and High-risk Non-muscle Invasive Bladder Cancer

Inclusion criteria

• Voluntary participation in the trial with signed informed consent;
• Patients aged ≥18 and ≤75 years, regardless of gender, with an expected survival of ≥2 years;
• Histologically confirmed non-muscle-invasive bladder urothelial carcinoma with positive PD-L1 expression. According to the 2014 guidelines of the Chinese Urological Association (CUA), patients are assessed as having a medium to high risk of recurrence or progression. (For patients considering a second transurethral resection, they may be included in the study after completing the procedure and if pathology confirms medium to high risk non-muscle-invasive bladder urothelial carcinoma);
• Performance status score (Eastern Cooperative Oncology Group, ECOG) of 0-2;
• Completion of screening-related examinations (complete blood count, coagulation function, liver and kidney function, infectious disease screening, 12-lead ECG, urinary system ultrasound, pelvic MR, and tissue pathology examination), without surgical contraindications.

Exclusion criteria

• Any of the following conditions:

Immune deficiency or impairment (such as AIDS patients), current use of immunosuppressive drugs or radiation therapy that may cause systemic BCG disease reaction; allergy to BCG components; patients with fever and acute infectious diseases, including active tuberculosis or those undergoing anti-tuberculosis treatment; those with severe chronic cardiovascular or cerebrovascular diseases or chronic kidney disease;

• Concurrent urogenital system tumors or tumors in other organs;
• Muscle-invasive bladder urothelial carcinoma (stage T2 and above) patients;
• Patients who have received chemotherapy, radiotherapy, or immunotherapy within the past 4 weeks (except immediate postoperative bladder instillation chemotherapy);
• Pregnant or lactating women, women of childbearing age not using effective contraception, or those planning to conceive during the trial period (including male participant partners);
• Known or suspected intraoperative bladder perforation;
• Presence of gross hematuria prior to enrollment, suspected unhealed surgical wounds or damaged urinary mucosa;
• Severe urethral stricture preventing cystoscopy, history of bladder contracture, or functional bladder volume less than 100mL;
• Accompanying cystitis, or those who have received other bladder instillation medications and have severe bladder irritation signs expected to affect the assessment of this study;
• Patients with various mental disorders, severe coagulation function, liver and kidney function, hematopoietic function disorders, etc., that cannot tolerate surgical treatment;
• Participation in other drug clinical trials within 3 months before enrollment;
• Known or suspected opioid or alcohol dependence;
• Any condition that the researcher believes may increase the risk to the participant or interfere with the execution of the clinical trial.