Intravesical Instillation of Hyaluronic Acid (Cystistat) for the Treatment of Category III Prostatitis: A...

Chronic nonbacterial prostatitis/chronic pelvic pain syndrome (CP/CPPS), classified as National Institutes of Health (NIH) category III prostatitis, is a common urological disorder, accounting for 90%-95% of prostatitis cases. Its pathogenesis involves inflammatory cascades along the bladder-prostate axis, neurogenic inflammation, and impairment of the mucosal barrier. Sodium hyaluronate (Cystistat), a glycosaminoglycan (GAG) layer replenishment agent, has demonstrated efficacy in treating bladder pain syndrome. However, its therapeutic role in CP/CPPS remains underexplored.

This study aimed to evaluate the clinical efficacy of intravesical hyaluronic acid (Cystistat) instillation in patients with CP/CPPS, identify potential predictive factors, and develop a predictive model to support personalized treatment strategies.

A retrospective analysis was conducted on 41 patients with CP/CPPS who received intravesical Cystistat between January 2023 and April 2024. NIH Chronic Prostatitis Symptom Index (NIH-CPSI) scores-including total score and subdomains (pain, urinary symptoms, and quality of life)-and visual analog scale (VAS) scores were compared before and after treatment using paired t-tests. Cohen's d was calculated to assess effect size. A treatment response was defined as a Global Response Assessment (GRA) score ≥2. Multivariate logistic regression was used to explore predictors of treatment response. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), with fivefold cross-validation and sensitivity analyses.

NIH-CPSI total scores significantly improved following treatment (25.71 ±  2.91 to 19.56 ±  4.28; mean change: -6.15 [95% CI: -7.27 to -5.02]; p < 0.001; Cohen's d  =  1.68). VAS scores also showed significant reduction (7.07 ± 1.07 to 4.16 ± 1.67; mean change: -2.91 [95% CI: -3.36 to -2.46]; p < 0.001; Cohen's d = 2.07). Improvements were observed across all NIH-CPSI subdomains, with the greatest effect noted in the pain domain (Cohen's d = 1.32). Overall, 70.7% of patients achieved a GRA score ≥2. Logistic regression identified that elevated C-reactive protein (CRP) levels (OR = 1.28, 95% CI: 0.90-1.82) were positively associated with response, while longer disease duration (OR = 0.98, 95% CI: 0.94-1.02) and lower maximum urinary flow rate (Qmax) (OR = 0.88, 95% CI: 0.67-1.15) were negatively associated. However, none of these associations reached statistical significance. A model incorporating CRP, disease duration, and Qmax yielded an AUC of 0.76 (cross-validated AUC: 0.73 ± 0.12). Sensitivity analyses confirmed the model's robustness across alternative definitions of treatment success.

Intravesical hyaluronic acid (Cystistat) therapy appears to be clinically effective for CP/CPPS, particularly in pain relief and quality-of-life improvement. Patients with elevated CRP levels and shorter disease duration may benefit more from this treatment. The derived predictive model offers a tool for individualized clinical decision-making. These findings lend indirect support to the "bladder-prostate axis" hypothesis, suggesting that Cystistat may alleviate pelvic pain by restoring bladder mucosal integrity and reducing inflammatory mediator activity. Future prospective randomized controlled trials are needed to validate these findings and further elucidate the underlying mechanisms. Further prospective, large-scale studies are needed to confirm efficacy, especially in OAB-associated subtypes, and refine predictive modeling approaches.