A randomized prospective study: hyaluronic acid versus standard therapy in bladder cancer local complications

Background: Hyaluronic acid is a glycosaminoglycan of the extracellular matrix. Scientific literature suggests a correlation between bladder inflammation and glycosaminoglycan layer absence. Many studies point out that hyaluronic acid intravesical somministration can reduce disabling symptoms, i.e. interstitial cystitis. It is possible to emphasize a satisfactory reduction of lower urinary tract symptoms due to intravesical immune or chemotherapy for bladder cancer. A preliminary Italian study underlines an improvement of quality of life recorded on patients who underwent intravesical hyaluronic acid instillations after the development of local toxicity after immuno or chemotherapy. Objectives: The primary end-point of this study is the evaluation of the effectiveness of therapy with hyaluronic acid, measured as reduction of voiding symptoms, compared to standard therapy (interruption of BCG/Immunotherapy instillations + antibiotic and antispasmodic therapy). The second end-points are: the reduction of inflammation at histopathology findings, the evaluation of the toxicity of the therapy and the possible improvement of cancer intravesical treatment. Patients and Methods: Patients with previous bladder cancer, suitable for immune-chemotherapy and who experienced a local toxicity (WHO grade II or III) were included in the study. During the visit, patients were invited to fill an international questionnaires like: VAS; IPSS; CPSE- NIH; ICQ-MLUTS; OAB-q SF and BCG symptoms questionnaire. Furthermore, we also collected: urinalysis; urine culture; renal-bladder ultrasound; cystoscopy and urine cytology. In the second step we randomized the patients in two main groups: Group A, therapy with intravescical hyaluronic acid according to the scheme:1 instillation (40 mg hyaluronic acid) to maintain inside the bladder for at least 30 minutes + 1 instillation/week for 6 weeks + 1 instillation/month for 3 months + 1 instillation/every 3 months as maintenance; Group B, standard therapy: oxybutynin hydrochloride 5 mg (2.5 mg × 3 times/die until the disappearance of the symptomatology) + ofloxacin 200 mg (1 co/12 hours for 10 days). The evaluation of efficacy of two therapies was performed after: 6 weeks; 3 months, 6 months and after one year by a new filling of the questionnaires: VAS, IPSS, CPSE-NIH, ICQ-MLUTS, OAB- q SF, BCG symptoms; and a new collection of exams: urinalysis, urine culture, renal-bladder ultrasound, cystoscopy and urine cytology. Results: We recruited 14 patients (8 Group A and 6 Group B). Group A-patients did not present at the moment side-effects after hyaluronic acid instillations and reported a subjective decrease in voiding symptoms. Two of them (2/8) dropped out of the study after tumor recurrence and subsequent radical cystectomy. Some patients of Group B (2/6) were forced to exit the protocol due to the development of intolerance to oxybutynin (severe urinary retention); others (3/6) presented mild side-effects (dry mouth); 1/6 finished the protocol with full benefit. Conclusion: In order to have a general view of the effectiveness of hyaluronic acid we plain toenrol more patients in this study. The analysis of the first results and the satisfaction of the patients are positive points to encourage the continuation of the use of intravesical hyaluronic acid.