Cystoscopic, histopathological, molecular and clinical characterization of Interstitial Cystitis/Bladder Pain Syndrome: the MUST Trial (Multicenter interstitial cystitis/bladder pain syndrome Trial)

Introduction. The absence of universally accepted clinical diagnostic criteria for Interstitial Cystitis (IC)/Bladder Pain Syndrome (BPS), negatively affects the progress in understanding this disease in terms of risk factors, pathogenesis, prognosis and therapy. What’s now emerging is the possible role of urinary and serum biomarkers in the diagnostic process and in the treatment of IC/BPS. They represent a non-invasive approach to assess the inflammatory status inside the bladder. The primary aim of our study was to evaluate the grade of correlation between cystoscopic, histopathological, molecular, and clinical data among women with IC/BPS. The secondary aim was to compare the same data between IC/BPS patients and a cohort of women undergoing under investigation exams for other reasons. Materials and methods. This is an observational multicenter prospective pilot study conducted by the Division of Female Pelvic Medicine and Reconstructive Surgery of Fondazione Policlinico Universitario A. Gemelli IRCCS and of Ospedale Isola Tiberina-Gemelli Isola, Rome, Italy in collaboration with Policlinico G. Martino, Messina, Italy. Preoperative workup consists of a comprehensive medical history, physical examination, urodynamic evaluation, collection of urinary and serum samples, bladder cystoscopy with hydrodistension and bladder biopsies. Analysis of accuracy of biomarkers was determined using area under the receiver operator characteristics curve (AUC). Statistical significance was set at p<.05 (95% confidence interval). Statistical analysis was performed using the SPSS Version 26.0 for Windows (SPSS Statistics UK, SPSS Inc, Chicago, IL, USA). Results. Between January 2022 and June 2024 60 patients were included in the study, 30 in the IC/BPS group and 30 in the control group. IC/BPS women had a significantly lower bladder capacity and an increased bladder sensibility in comparison with the controls. IC/BPS patients showed a greater premature filling sensation and reduced bladder capacity compared to the control group. Women with lower urodynamic first desire to void (FD) had a significative higher possibility to have IC/BPS (RR 7.161, p=0.007). The comparison between non-HL-IC/BPS group and the control group didn’t reveal significant differences in bladder biopsies. We identified 4 urinary metabolic analytes capable of segregating IC/BPS women from N IC/BPS women; each of these analytes had individual AUCs greater than 0.8. When combined into a single model, the AUC was 0.917, with high sensitivity and specificity. Contrarily serum markers didn’t appear to have diagnostic power in the diagnosis of IC/BPS. Conclusion. Data coming from this pilot study strongly suggest that urine, but not serum, is a potential resource for screening IC/BPS women in the clinical setting. Traditional cystoscopy with bladder biopsies under anesthesia doesn’t play a significant role in discriminating IC/BPS from other similar diseases considering also the absence of correlation between inflammatory status and severity of symptoms. Nevertheless, due to the preliminary nature of the study, these results will need thorough validation.