Intravesical immunotherapy with Bacillus Calmette-Guérin (BCG) is the recommended treatment for patients with intermediate and high-risk non-muscle invasive bladder cancer (NMIBC) after complete tumor resection. Discontinuation or suspension of this therapy is often due to local side effects. The most common local adverse event, reported in approximately 80% of patients, is BCG-related chemical cystitis, a condition characterized by storage lower urinary tract symptoms, like frequency and urgency, and haematuria or pain during urination. Aim of the study was to evaluate the efficacy of sequential intravesical instillations of combined hyaluronic acid (HA) and chondroitin sulfate (CS) in reducing local BCG toxicity and urinary symptoms in a large samples.

This was a multicentric prospective study. Patients underwent BCG intravesical administration after Transurethral Resection of Bladder Tumour (TURBT) for intermediate/ high risk NMIBC. We set the baseline when the patient has completed the induction cycle with six weekly intravesical BCG instillation. 3- day voiding diary, the International Prostate Symptom Score (IPSS) and VAS score (to evaluate bladder pain; 0: best- 10: worst) were evaluated at baseline. Patients who continued the maintenance treatment received an intravesical (i) instillation of HA+CS after every BCG instillation. Follow- up was at 6 months (after other 6 BCG- instillations, each followed by an iHA+CS). Student’s t-test and Chi square test were used to compare continuous and categorical variables respectively. All analyses were performed using StataCorp. 2023.

We enrolled 63 male patients. Median age was 61 (44- 79) yrs. Storage symptoms, IPSS and VAS score significantly decreased  (p<0.01) at 6 months follow- up (Table 1). Transurethral catheterization and HA+CS bladder instillations were well tolerated. No local or major side effects were reported during or after treatment. No drop- our was observed.

In order to decrease BCG’s side effects many approaches have been proposed. The rationale for using (i)HA+CS is to promote early repair of the GAGs​ ​layer avoiding the cycle of chronic bladder inflammation and hypersensitization. Furthermore, HA directly interacts with the cell surface, reducing urothelium permeability and favoring the binding to cellular receptors which reduce production of inflammatory cytokines. Because of (i)HA+CS documented also anti-inflammatory and protective activity on the urothelium we considered the possible use of these devices on the treatment of BCG induced cystitis. Our results are in line with published data but we presented the largest population size so far in the literature.

This study demonstrated that adding (i)HA+CS significantly reduce storage urinary symptoms (particularly urinary frequency and urgency) and pelvic pain in patients underwent to BCG instillations. This therapy could therefore improve patient adherence, thus reducing the drop-out related to BCG side effect.

Continence 12S (2024) 101604
DOI: 10.1016/j.cont.2024.101604