Intravesical administration of highly concentrated hyaluronic acid and chondroitin sulfate as add-on therapy for chemical cystitis induced by Bacillus Calmette–Guérin (BCG) immunotherapy

Purpose: Intravesical (i) 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. Aim of the study was to evaluate the efficacy and safety of sequential intravesical instillations of combined hyaluronic acid (HA) and chondroitin sulfate (CS) in reducing local BCG toxicity and urinary symptoms. Methods: This was a prospective, multicentric study. Patients underwent BCG intravesical administration after Transurethral Resection of Bladder Tumor (TURBT) for intermediate/high-risk NMIBC. Patients underwent to HA + CS instillations after every (i) BCG (Group A) were compared with a control group (Group B) that included patient underwent only to BCG instillations, during the maintenance period. 3-day voiding diary, the International Prostate Symptom Score (IPSS), IPSS quality-of-life index (IPSS-QoL), and VAS score (to evaluate bladder pain) were evaluated at baseline and at 1-, 3-, and 6-month follow- up. Results: One hundred-eighteen patients were included (Group A: 63 patients, Group B: 55 patients). Mean value of IPSS, IPSS-QoL, and VAS score has significantly increase in Group A at 1-, 3-, and 6-month follow-up (p < 0.00). Group A showed also a significant improvement about irritative lower urinary symptoms (LUTS), which was maintained in the 6-month follow-up, as opposed to Group B that demonstrated a worsening in urinary symptoms during all follow-up (p < 0.00). No local or major side effects were reported during or after treatment. Conclusion: This study demonstrated that adding (i) HA + CS significantly reduces storage symptoms, pelvic pain, and day-time urinary frequency in patients with BCG-induced chemical cystitis. This therapy could therefore improve patient adherence, ensuring better adherence and lower drop-out rates.