Intravesical Hyaluronic Acid (HA) for Preventing Radiation Cystitis on Bladder Cancer

Study Design: Single-blind, Randomized, Controlled trial.

• Primary endpoint

• To assess patient-reported outcomes (PROs) related to symptoms of radiation-induced cystitis in patients with bladder cancer undergoing radiotherapy.
• Secondary endpoint

• To evaluate tumor control rates in patients with bladder cancer undergoing radiotherapy.
• To assess the incidence and severity of radiation-induced cystitis using RTOG/EORTC criteria, CTCAE grading, and cystoscopic findings.
• To compare healthcare costs between the treatment group receiving intravesical hyaluronic acid instillation and the control group.

Inclusion criteria

• Pathologic confirmed Muscle-Invasive Urothelial Carcinoma I. Clinical stage: T2-T4a MIBC II. No or limited nodal involvement (N0 or partial N1, only isolated or regional) III. No distant metastasis (M0) IV. Transurethral resection of bladder tumor (TURBT): Maximal TURBT is available > Most tumors must be resected, and residual disease should be minimized.

V. Preserved bladder function is required: patients must have normal bladder capacity and maintain adequate voiding function.

VI. Unifocal or localized tumor (except multifocal) VII. No extensive carcinoma in situ (CIS)

• Age ≥ 19
• Karnofsky performance score (KPS) ≥ 70 or ECOG performance status 0~2
• Patients who are candidates for bladder-preserving therapy, specifically those scheduled to undergo concurrent chemoradiotherapy (CCRT) instead of radical cystectomy.
• Patients scheduled to receive radiotherapy in combination with one or more of the following chemotherapeutic agents prior to study enrollment: Cisplatin-based chemotherapy (e.g. weekly cisplatin), Gemcitabine or 5-FU/mitomycin, in accordance with standard clinical practice.
• Written informed consent obtained from the patients prior to study participation

Exclusion criteria

• Present of distant metastasis (M1)
• Tumor invasion beyond the bladder wall into adjacent organs (T4b)
• Non-urothelial carcinoma (including histologic variant) or predominant of non-urothelial components in mixed histology
• Medically inoperable status or poor general condition (ECOG performance status > 2)
• History of active cystitis or recurrent urinary tract infections within the past 6 months
• Known hypersensitivity to hyaluronic acid or related compounds
• Any condition in which, in the investigator's judgment, administration of the study drug or procedure is deemed inappropriate
• Pregnant or breastfeeding women, or women of childbearing potential who are unable or unwilling to use adequate contraception during the study period