Multicentre International Study for the Prevention with iAluRil of Radio-induced Cystitis (MISTIC): A Randomised Controlled Study

Abstract

Background: Radiation-induced cystitis is a common side effect of radiotherapy (RT) to the pelvic area. Hyaluronic acid (HA) and chondroitin sulfate (CS) are components of the urothelial mucosa and positive results have been obtained for intravesical HA/CS instillations for the treatment of urinary tract infections and bladder pain syndrome. HA/CS may also have a protective effect against RT bladder toxicity.

Objective: To investigate whether HA and CS protect the urothelium during RT, alleviate lower urinary tract symptoms, and improve quality of life.

Design setting and participants: This multicentre randomised controlled trial was conducted across seven centres in four countries. Male patients aged ≥18 yr scheduled to undergo primary intensity-modulated radiotherapy for localised prostate cancer were enrolled.

Intervention: Patients were randomised to intravesical HA/CS plus an oral formulation of curcumin, quercetin, HA, and CS (group A) or no treatment (group B).

Outcome measurements and statistical analysis: The primary endpoint was absolute changes from baseline to follow-up in urinary domain scores for the Expanded Prostate Cancer Index Composite (EPIC), the International Consultation on Incontinence Questionnaire-Male Lower Urinary Tract Symptoms (ICIQ-MLUTS), and the EuroQol Group EQ-5D-5L questionnaire. Data analysis for efficacy and safety outcomes was performed using an intention-to-treat (ITT) approach; the ITT population was defined as all randomised patients.

Results and limitations: Of 57 patients screened, 49 were enrolled and randomly assigned to either active treatment (group A, n = 25) or the control (group B, n = 24). Three patients in the control group withdrew after randomisation. Changes from baseline to 12 mo were worse in the control group for subtotal scores for urinary symptoms and impact of symptoms on quality of life and for the total score (p = 0.05, p = 0.003, and p = 0.008, respectively). There was a significant time × group interaction in favour of active treatment for the incontinence symptom score (p = 0.011) and bother score (p = 0.017). The absence of a sham procedure and/or placebo is the main limitation.

Conclusions: Our results suggest that intravesical HA/CS in combination with an oral formulation may reduce urinary symptoms and improve QoL at short-term (1 yr) follow-up.

Patient summary: We investigated whether hyaluronic acid (HA) and chondroitin sulfate (CS) have a protective effect against the bladder toxicity of radiotherapy for prostate cancer. HA/CS used for weekly bladder irrigation for 6 wk and given orally with curcumin and quercetin for 12 wk reduced urinary incontinence symptoms and bother measured at 1-year follow-up. This may hold promise as a preventive treatment if the results are confirmed in further trials.

Keywords: Chondroitin sulfate; Cystitis; Hyaluronic acid; Lower urinary tract symptoms; Prostate cancer; Quality of life; Questionnaries; Radiotherapy.

Fig. 1

Flowchart of patient inclusion in the trial.

Fig. 2

Repeated-measures analysis of variance for the urinary domain of the Expanded Prostate Cancer Index Composite (EPIC). Data are presented as mean ± standard deviation.

Fig. 3

Repeated-measures analysis of variance for the International Consultation on Incontinence Questionnaire-(ICIQ) Male Lower Urinary Tract Symptoms. Data are presented as mean ± standard deviation.

Fig. 4

Repeated-measures analysis of variance for the EuroQol Group EQ-5D-5L questionnaire. Data are presented as mean ± standard deviation.