Therapeutic Efficacy of Multimodal Therapy for Patients with Interstitial Cystitis/ Bladder Pain Syndrome Refractory to Previous Bladder Monotherapy

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This study evaluated the efficacy of intensive multimodal therapy (MMT) for IC/BPS based on individualized clinical assessments within a 3-month period. Methods Thirty-one patients with IC/BPS who had failed prior monotherapy were enrolled. Following comprehensive evaluation, patients received tailored MMT, which could include anti-inflammatory medications, intravesical hyaluronic acid instillation, intravesical or urethral botulinum toxin A (BoNT-A) injection, pelvic floor BoNT-A injection, platelet-rich plasma injection, low-energy shockwave therapy, pelvic floor massage for pelvic floor muscle pain (PFMP), and/or medications for anxiety, depression, voiding dysfunction, or bladder hypersensitivity. The primary outcome was assessed at 3 months using the global response assessment (GRA), with a successful response defined as a GRA score of 2 or 3. Patients were followed for up to 1 year. Results Of the 31 patients (28 women, 3 men), 18 (58.1%) reported a successful outcome at 3 months. Successful and unsuccessful subgroups showed significant improvements in symptom scores and glomerulation grade after cystoscopic hydrodistention. However, reductions in pain VAS and daytime frequency were observed only in the successful subgroup. Similarly, PFMP parameters improved significantly in the successful subgroup but not in the failed subgroup. Sustained therapeutic effects were observed in 21 patients (67.7%) at 9 months and in 23 patients (74.2%) at 1 year after MMT. Conclusion Multimodal bladder therapy, incorporating bladder- and extra-bladder–targeted approaches, yields satisfactory outcomes in patients with IC/BPS unresponsive to prior monotherapy. Figures Figure 1 Introduction Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic, debilitating condition of unknown etiology, characterized by urinary urgency, frequency, and suprapubic pain associated with bladder filling 1 . Current oral pharmacological therapies often fail to fully relieve bladder pain or improve bladder capacity. Consequently, pelvic floor-directed interventions, including physical therapy, injections, and nerve blocks, have been explored 1 . Intravesical hyaluronic acid instillation and intravesical botulinum toxin A (BoNT-A) injection have demonstrated efficacy in alleviating bladder symptoms in patients with IC/BPS 2 . Autologous platelet-rich plasma (PRP), which is enriched with growth factors and cytokines involved in inflammation modulation and tissue regeneration, has also emerged as a potential therapy 3 . Furthermore, low-energy shock wave (LESW) bladder therapy has recently been explored as a regenerative approach for IC/BPS 4 . However, neither conventional nor novel therapies have been able to deliver durable treatment outcomes 5 . Psychological comorbidities such as anxiety and depression are frequently observed in patients with IC/BPS 6 . Many patients further report pelvic organ discomfort and a variety of systemic complaints, including gastroesophageal reflux disease, myofascial pain, insomnia, depression, and anxiety 7 . Pelvic floor muscle pain (PFMP) and voiding dysfunction, often related to urethral sphincter dysfunction or poor pelvic floor muscle relaxation, are also common 8 . Most available treatments provide only partial and temporary symptom relief, likely due to the poorly understood pathophysiology of IC/BPS and its heterogeneous clinical subtypes 9 . Although bladder-directed monotherapies have limited efficacy, combining bladder- and extra-bladder-targeted therapies may better address the multifactorial mechanisms underlying IC/BPS and achieve more durable outcomes 10 . This clinical study aimed to treat patients with IC/BPS who had not responded to monotherapy by applying intensive multimodal therapy (MMT) over a 3-month period. We hypothesized that MMT, tailored to individual clinical assessments and cystoscopic findings, could offer superior and more sustained efficacy compared with monotherapy. Materials and Methods This prospective preliminary clinical study enrolled 31 patients with IC/BPS who had failed bladder monotherapy for at least 3 months. All eligible patients underwent comprehensive evaluation, including assessment of anxiety and depression severity indices, interstitial cystitis symptom index (ICSI), interstitial cystitis problem index (ICPI), bladder pain visual analog scale (VAS; 0–10, from none to severe pain), bladder capacity, and cystoscopic hydrodistention findings (maximal bladder capacity [MBC] and glomerulation grade under anesthesia). Voiding function was assessed using videourodynamic studies, and pelvic floor examination was performed to identify tender points, pain VAS scores, and overall pelvic floor muscle pain (PFMP) scores. Patients were instructed to complete a 3-day voiding diary documenting daytime and nighttime frequency. The maximal bladder capacity recorded in the diary was defined as the functional bladder capacity (FBC). Clinical symptoms were further evaluated using the O’Leary–Sant Symptom Score (OSS, including ICSI and ICPI) and bladder pain VAS. Additional psychological assessments included the perceived pressure scale (PPS), type D personality scale, interpersonal support evaluation list, Beck Anxiety Inventory, and Beck Depression Inventory. Videourodynamic study (VUDS) was performed in all patients to evaluate bladder function and exclude bladder outlet obstruction (BOO), neurogenic dysfunction, or normal bladder findings. Patients were excluded if they demonstrated a FBC > 350 mL on voiding diary, anatomical BOO during the voiding phase, or a low-compliance contracted bladder. Following VUDS, a potassium chloride solution (0.4 M) was instilled intravesically, and the test was considered positive if the patient reported bladder pain or urgency. Cystoscopic hydrodistention was performed under intravenous anesthesia. Intravesical pressure was maintained at 80 cm H₂O until the bladder was fully distended, at which point MBC was measured. After drainage, the bladder wall was inspected for glomerulation, which was graded as follows: 0 = none, 1 = present in 1–2 quadrants, 2 = present in 3–4 quadrants, 3 = splotch or rainfall hemorrhage, and 4 = cracks or mucosal fissures 11 . Hunner-type IC (HIC) was defined as the presence of Hunner lesions with or without glomerulation, which are typically identifiable during office cystoscopy without anesthesia 12 . Following evaluation, patients received individualized bladder- and extra-bladder-targeted therapies according to their symptoms and clinical assessments. Treatment options included anti-inflammatory medications, intravesical hyaluronic acid instillation, intravesical BoNT-A or PRP injection, urethral sphincter BoNT-A injection, PFM BoNT-A injection, LESW, pelvic floor massage for PFMP, and medications for voiding dysfunction, bladder hypersensitivity, or psychological stress. Specific treatment selection was guided by the clinical assessment findings (Table 1 ). Table 1 Suggested treatment modalities selected based on the clinical assessment results Clinical Assessment Criteria Treatment modality 1.IC symptom score ICSI ≥ 12 NSAID, analgesic, narcotic drugs for 3 months 2. Bladder pain VAS score (0–10) ≥ 5 Intravesical BoNT-A 100U injection x 1 3. Glomerulation after HD ≥ Grade 2 Intravesical PRP injections Q1M x 4 4. Glomerulation after HD Any grade Bladder instillation of heparin, Hyaluronic acid every 1–2 weeks 5. Presence of Hunner’s lesion Yes Electrofulguration or laser ablation of Hunner’s lesions, triamcinolone injection 6. Pelvic floor focal tenderness VAS ≥ 3 PFM BoNT-A 100U local injection x 1 7. Pelvic floor muscle tenderness Any grade LESW and PFM physiotherapy every 1 week 8. Urethral sphincter dysfunction Yes Urethral sphincter BoNT-A 100U injection x 1 9. Anxiety and depression BAI ≥ 18 Oral antianxiety or antidepressant medication 10. Bladder hypersensitivity Yes Medication for bladder hypersensitivity, intravesical triamcinolone injection 11. Voiding dysfunction Yes Alpha-blocker, baclofen 12. Hunner’s lesion with virus infection Elevated EB title Antiviral agent, Valacyclovir for 3 months IC: interstitial cystitis, ICSI: interstitial cystitis symptom index; NSAID: non-steroid anti-inflammatory drugs, HD: cystoscopic hydrodistention; BoNT-A: botulinum toxin A; HA: hyaluronic acid; LESW: low energy shock wave; PRP: platelet-rich plasma, PFM: pelvic floor muscle; VAS: visual analog scale for pain; BAI: Beck’s anxiety index The primary endpoint was the change in OSS from baseline to 3 months after the first injection treatment. Secondary endpoints included bladder pain VAS, daytime frequency, nocturia episodes, FBC from the 3-day voiding diary, Qmax, voided volume, PVR volume, and global response assessment (GRA). Cystoscopic hydrodistention was performed at baseline and again 3 months after treatment initiation. Treatment outcomes were evaluated using the GRA scale ranging from − 3 to + 3. Patients achieving a GRA of 2 or 3 after MMT were considered treatment successes; all others were classified as failures 1 . Follow-up continued for up to one year after MMT completion, or until symptom relapse requiring further bladder treatment. Success rates were assessed at 3, 6, 9, and 12 months after the first treatment day. Adverse events were also recorded, including urinary tract infection (UTI), acute urinary retention, high PVR (> 250 mL), dysuria, and micturition pain. This clinical study was approved by the Institutional Review Board and Ethics Committee of the hospital (IRB: 113-023-A, dated December/05/2024). All participants were informed of the study rationale, and written consent was obtained. Statistical analysis Continuous variables were expressed as mean ± standard deviation, while categorical variables were presented as counts and percentages. Differences in clinical data between the successful and failed subgroups, as well as changes in variables after MMT, were analyzed using one-way analysis of variance. A p -value < 0.05 was considered statistically significant. Statistical analyses were performed using Statistical Package for the Social Sciences, version 20.0 (IBM Corp., Armonk, NY, USA). Results Among the 31 patients who completed MMT, 28 were women and 3 were men. HIC was identified in 1 patient, while 30 had NHIC. All had previously received intravesical BoNT-A, PRP, or LESW therapy without success. The specific bladder and extra-bladder therapies included in MMT are summarized in Table 1 . At 3 months, treatment success was achieved in 7/8 patients (87.5%) who received intravesical BoNT-A, 10/14 (71.4%) who underwent PFM BoNT-A injection for PFMP, and 13/20 (65.0%) who received PFM massage. Overall, 18/31 patients (58.1%) reported successful outcomes at 3 months, including 10 with GRA = 2 and 8 with GRA = 3. Of the remaining 13 patients, 9 had GRA = 1 and 4 had GRA = 0. Comparison of baseline clinical symptoms, cystoscopic findings, 3-day voiding diaries, PFM examinations, and VUDS results revealed no significant differences between the successful and failed subgroups. Following MMT, both groups demonstrated significant improvement in ICSI, ICPI, and glomerulation grade. However, significant reductions in bladder pain VAS, PPS, and daytime frequency episodes were observed only in the successful subgroup ( Table 2 ). Notably, as glomerulation grade decreased, MBC significantly increased in the failed subgroup. Table 2 Symptom scores, cystoscopic findings, and voiding diary records at baseline and 3 months after multimodal therapy in patients with successful and failed treatment outcomes. Time Total patients (n = 31) Failure (GRA = 0,1) (n = 13) Successful (GRA = 2,3) (n = 18) p-value Age 47.1 ± 15.5 57.9 ± 9.27 0.039 ICSI Baseline 13.7 ± 3.68 13.9 ± 3.86 13.4 ± 3.65 0.728 3M 8.9 ± 3.35* 10.2 ± 3.52* 7.94 ± 2.96* 0.059 ICPI Baseline 12.3 ± 3.08 12.7 ± 2.63 12.1 ± 3.42 0.579 3M 8.52 ± 3.6* 10.6 ± 2.93* 7.0 ± 3.31* 0.004 VAS Baseline 5.94 ± 2.39 5.77 ± 2.39 6.06 ± 2.46 0.748 3M 3.61 ± 2.29* 4.85 ± 2.51 2.72 ± 1.67* 0.008 PPS Baseline 17.9 ± 7 .39 19.9 ± 8.09 16.5 ± 6.72 0.219 3M 15.3 ± 6.69* 18.1 ± 6.49 13.3 ± 6.27* 0.050 DS14 Baseline 23.2 ± 11.1 23.5 ± 11.2 22.9 ± 11.3 0.886 3M 23.8 ± 9.88 27.4 ± 10.0 21.2 ± 9.21 0.087 ISEL-16 Baseline 24.3 ± 5.81 25.2 ± 6.07 23.7 ± 5.71 0.491 3M 25.3 ± 4.21 23.6 ± 4.13 26.4 ± 3.96 0.064 BAI Baseline 13.8 ± 11.3 14.4 ± 14.2 13.4 ± 9.16 0.824 3M 14.4 ± 11.6 17.9 ± 14.1 11.9 ± 8.99 0.200 BDI Baseline 15.0 ± 12.7 18.4 ± 15.9 12.6 ± 9.65 0.214 3M 13.0 ± 10.6 16.5 ± 11.4 10.4 ± 9.48 0.112 MBC (ml) Baseline 782 ± 177 715 ± 191 831 ± 154 0.073 3M 887 ± 160* 854 ± 195* 908 ± 133 0.372 Glomerulation Baseline 1.87 ± 0.76 2.15 ± 0.69 1.67 ± 0.77 0.079 3M 1.06 ± 0.85* 1.46 ± 0.78* 0.78 ± 0.81* 0.025 Frequency Baseline 12.5 ± 4.93 13.7 ± 6.48 11.6 ± 3.36 0.295 3M 11.3 ± 4.34* 13.5 ± 5.13 9.73 ± 2.9* 0.015 Nocturia Baseline 2.24 ± 1.43 2.56 ± 1.85 2 ± 1.04 0.290 3M 2.19 ± 1.34 2.75 ± 1.69 1.79 ± 0.85 0.046 FBC (ml) Baseline 291 ± 108 292 ± 133 291 ± 89.2 0.981 3M 267 ± 103 235 ± 93.6* 291 ± 105 0.127 PFM most tendered VAS Baseline 5.0 ± 3.22 4.73 ± 3.74 5.18 ± 2.94 0.726 3M 3.46 ± 3.13* 4.73 ± 3.47 2.65 ± 2.69* 0.086 PFMP VAS Baseline 2.18 ± 0.94 2 ± 1 2.29 ± 0.92 0.432 3M 1.71 ± 0.85* 2.09 ± 0.94 1.47 ± 0.72* 0.059 PFMP points Baseline 2.61 ± 2.25 2.45 ± 2.5 2.71 ± 2.14 0.779 3M 1.46 ± 1.53* 1.82 ± 1.66 1.24 ± 1.44* 0.333 Pdet (cmH2O) Baseline 19.4 ± 10.8 21.5 ± 8.07 17.6 ± 12.7 0.381 3M 20.9 ± 8.84 19.7 ± 6.57 22 ± 10.7 0.372 Qmax (ml/s) Baseline 10.3 ± 6.44 8.46 ± 3.64 11.6 ± 7.71 0.183 3M 12.5 ± 6.93 8.85 ± 4.34 15.1 ± 7.37 0.011 Volume (ml) Baseline 188 ± 101 166 ± 69.1 204 ± 118 0.315 3M 204 ± 98.2 150 ± 78.4 243 ± 94.1 0.007 PVR (ml) Baseline 37.1 ± 79.3 57.3 ± 115 22.4 ± 34.3 0.233 3M 30.6 ± 43.9 36.2 ± 45.0 26.6 ± 43.9 0.554 FSF (ml) Baseline 126 ± 37.4 124 ± 33.6 127 ± 40.9 0.832 3M 123 ± 54.7 98 ± 51.7 140 ± 50.9 0.030 FS (ml) Baseline 211 ± 63.4 207 ± 67.6 214 ± 62.0 0.762 3M 199 ± 75.8 156 ± 64.2* 229 ± 69.9 0.006 US (ml) Baseline 235 ± 81.2 229 ± 80.4 239 ± 84.0 0.741 3M 220 ± 78.3 168 ± 53.0* 256 ± 73.9 0.001 Compliance (ml/cmH2O) Baseline 74.8 ± 86.1 38.8 ± 14.6 101 ± 10 6 0.025 3M 71.0 ± 60.3 58.5 ± 45.3 80.0 ± 69.0 0.335 BCI Baseline 74.0 ± 32.7 65.6 ± 23.5 81.1 ± 38.4 0.255 3M 77.2 ± 31.2 62.5 ± 25.7 90.8 ± 30.6 0.034 CBC (ml) Baseline 225 ± 102 224 ± 81.7 226 ± 117 0.946 3M 235 ± 88.8 186 ± 65.4 269 ± 88.5 0.008 BOOI Baseline -2.46 ± 18.9 3.82 ± 6.85 -7.77 ± 24.0 0.119 3M -1.61 ± 15.7 2.64 ± 9.86 -5.5 ± 19.2 0.372 * P < 0.05, GRA: global response assessment, ICSI: interstitial cystitis symptom index, ICPI: interstitial cystitis problem index, VAS: visual analog scale of pain, PPS: perceived pressure scale, DS14: type D personality scale, ISEL16: interpersonal support evaluation list, BAI: Beck’s anxiety index, BDI: Beck’s depression index, MBC: maximal bladder capacity, FBC: functional bladder capacity, VAS: visual analog scale of pain, PFMP: pelvic floor muscle pain, Pdet: detrusor pressure, Qmax: maximum flow rate, PVR: post-void residual, FSF: first sensation of filling, FS: fullness sensation, US: urge sensation, BCI: bladder contractility index, CBC: cystometric bladder capacity, BOOI: bladder outlet obstruction index. PFMP parameters—including the pain score of the most tender point, overall PFMP VAS, and the number of PFMP sites—showed significant improvement in the successful subgroup but not in the failed subgroup. In contrast, VUDS parameters did not demonstrate significant changes in either group. Patients with failed outcomes were noted to have decreased bladder fullness and urgency sensation volumes. Following the primary endpoint, the success rate of MMT was 51.6% (16/31) at 6 months, rising to 67.7% (21/31) at 9 months and 73.1% (23/31) at 12 months. Notably, five patients who had initially failed treatment at 3 months showed gradual improvement during follow-up. By 12 months after the first treatment, only 8 patients (26.9%) required additional bladder therapy. Discussion This study demonstrated that 58.1% of patients with IC/BPS who had failed prior bladder therapies achieved successful outcomes at 3 months following MMT, based on clinical assessments and tailored combinations of bladder and extra-bladder treatments. The success rate further increased to 73.1% at 1 year. Among the treatment modalities, intravesical BoNT-A injection and PFM therapy yielded the highest rates of success. Patients with favorable outcomes also experienced significant reductions in PFM pain and tender points. These findings suggest that IC/BPS may arise from heterogeneous underlying mechanisms, making monotherapy insufficient for many patients, while a multimodal therapeutic approach can provide more durable benefits. Various pathogenic mechanisms of IC/BPS have been proposed from clinical and animal studies 9 . These include bladder inflammation with urothelial injury, suburothelial inflammation, pan-cystitis characterized by chronic inflammatory infiltration of the suburothelium and detrusor muscle, chronic scarring within the bladder wall, and central nervous system involvement with heightened inflammatory activity in the dorsal root ganglia and sacral spinal cord segments 13 . Considering this multifactorial pathogenesis, identifying a single initiating factor or optimal treatment target remains challenging. Therapeutic strategies are therefore often guided by the nature and severity of bladder and nervous system pathology 14 . In line with this, the revised AUA guidelines for IC/BPS have abandoned tiered treatment recommendations and instead advocate MMT to address both bladder-specific and systemic symptoms simultaneously, thereby offering the potential for more durable and effective outcomes 13 . Management of IC/BPS should be tailored according to subtype, with different approaches for HIC and NHIC. For patients diagnosed with HIC, the first-line therapy is cystoscopic ablation of Hunner’s lesions, typically using electrofulguration or laser ablation 13 . In this study, we additionally applied PRP combined with triamcinolone to the lesion sites after fulguration, a strategy previously reported to yield encouraging preliminary results 15 . Patients often experienced rapid pain relief and favorable re-epithelialization at treated sites. Notably, Epstein–Barr virus has been detected in the bladder walls of patients with HIC 16 , leading to exploration of adjunctive antiviral therapy with low-dose valacyclovir following lesion ablation 17 . Although only one patient with HIC was enrolled in this study, she achieved a successful treatment outcome. Earlier guidelines stratified treatment according to symptom severity and the invasiveness of bladder-directed interventions 18 . Currently available oral pharmacotherapies—including nonsteroidal anti-inflammatory drugs, corticosteroids, antihistamines, anticholinergics, β3-adrenoceptor agonists, cyclosporine, and analgesics—have shown only limited efficacy in relieving symptoms or eradicating bladder pain in IC/BPS 13 . Intravesical therapies such as glycosaminoglycan (GAG) instillations and BoNT-A injections can provide short-term benefit, but long-term durability remains limited for most patients 19 . Although intravesical BoNT-A injection is listed in the AUA guidelines, it is generally considered secondary to GAG supplementation therapy 20 . In practice, BoNT-A injections are used to mitigate chronic inflammation and suppress inflammation-induced apoptotic pathways 19 . Clinical studies have demonstrated that intravesical BoNT-A reduces bladder pain and IC symptom scores while increasing FBC 21 . Immunohistochemical analyses further support these findings, showing reduced apoptotic activity and mast cell infiltration, alongside increased Ki-67 and E-cadherin expression. Moreover, repeated intravesical BoNT-A injections at 6-month intervals have been associated with reductions in glomerulation severity during cystoscopic hydrodistention 21 . In this study, we observed that MMT incorporating intravesical BoNT-A injection achieved a high success rate in patients with elevated bladder pain VAS, while PFM BoNT-A injection was particularly effective in patients with PFMP. These findings suggest that BoNT-A injections can effectively suppress chronic bladder inflammation and provide pain relief both in the bladder and pelvic floor muscles. Chronic inflammation-induced sensory hyper-innervation is recognized as a key pathophysiological mechanism underlying IC/BPS symptoms 22 , 23 . The therapeutic effect of BoNT-A appears to be superior to other novel therapies such as PRP injection or LESW bladder therapy. Regenerative strategies, including intravesical PRP therapy and LESW, aim to reduce chronic inflammation and enhance urothelial proliferation and maturation. However, their efficacy remains limited, as persistent inflammation often hampers durable outcomes 24 . These bladder-focused treatments address selected aspects of IC/BPS pathophysiology but are insufficient to fully resolve its multifactorial nature, particularly in refractory cases. Nevertheless, adjunctive use of PRP in patients with high-grade glomerulation, and LESW in those with PFM tenderness, demonstrated additional benefit, as reflected by reductions in glomerulation grade and PFMP severity in the failed subgroup. Importantly, our results show that the success rate of MMT increased from 3 months to 9 and 12 months, suggesting that bladder condition progressively improves over time with adequate anti-inflammatory and regenerative therapy. Although there was a slight decline in response at 6 months, this may be due to unresolved bladder inflammation following initial intravesical injection therapies. With continued treatment, inflammation subsides, urothelial integrity is restored, and barrier function improves, as evidenced by the reduction in glomerulation grade during follow-up cystoscopic hydrodistention. Anxiety, depression, and psychological stress are commonly associated with IC/BPS and can exacerbate symptoms by disrupting urothelial integrity and provoking symptom flares 25 . Stress is strongly correlated with symptom severity, particularly in patients who are refractory to conventional therapies. Mechanistically, stress may compromise the bladder’s mucosal barrier, increase urothelial permeability, thereby inducing irritation and pain. Previous studies have shown that patients with severe IC/BPS often present with higher levels of anxiety and depression 26 . Incorporating psychiatric consultation alongside bladder-targeted therapies has been reported to reduce symptom indices; however, current evidence has not yet demonstrated the superiority of multimodal approaches that include psychiatric support or PFM therapy over monotherapy in IC/BPS management 27 . Beyond bladder pathology, extra-bladder conditions such as PFM dysfunction, fasciitis, visceral inflammation, irritable bowel syndrome, endometriosis, and other pelvic organ disorders can provoke bladder pain and irritative symptoms via cross-organ communication within the central nervous system 28 . Myofascial pain syndrome is particularly common among patients with nonbladder-centric IC/BPS. On physical examination, many such patients demonstrate PFMP with palpable trigger points 29 . In these cases, bladder-directed therapies alone are typically insufficient, as the primary pain source originates from the PFM. BoNT-A injections at PFM tender points have been shown to effectively alleviate PFMP in patients with IC/BPS accompanied by pelvic floor hypertonicity 30 . In our study, extra-bladder therapies were added for patients with PFM tenderness. Interventions such as PFM BoNT-A injections and PFM physiotherapy, with or without LESW therapy, significantly reduced PFMP severity and tender points, further supporting the therapeutic value of targeting PFMP in this patient population. This study is the first clinical investigation to demonstrate the efficacy of MMT in treating patients with IC/BPS who had failed prior bladder-directed therapies. The rationale for MMT is grounded in the complex and multifactorial pathophysiology of IC/BPS, which often necessitates the integration of multiple therapeutic strategies. Depending on the predominant clinical features and concomitant treatment for bladder pain, bladder hypersensitivity, urothelial dysfunction, PFMP, psychological distress, and coexisting organ dysfunction, MMT can provide a satisfactory outcome. Although these interventions vary in mechanism and target distinct pathophysiological pathways, their combined use enables durable and meaningful clinical improvements in patients with IC/BPS who do not respond to monotherapy. Conclusion A precision-driven diagnostic approach that stratifies patients with IC/BPS into clinical subtypes based on distinct pathophysiological profiles and symptom characteristics may facilitate more tailored and effective management. 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Sutherland S, Grace Kelly A, Ryden A, Dmochowski RR, Reynolds WS, McKernan LC. Compensatory coping and depression in women with interstitial cystitis/bladder pain syndrome. Neurourol Urodyn. 2023;42(1):322-329. Yu WR, Jhang JF, Chen BY, Ou SR, Li HM, Kuo HC. Multimodal Treatment with Cognitive Behavioral Therapeutic Intervention Plus Bladder Treatment Is More Effective than Monotherapy for Patients with Interstitial Cystitis/Bladder Pain Syndrome-A Randomized Clinical Trial. J Clin Med. 2022;11:6221. Lackner JM, Clemens JQ, Radziwon C, et al. Cognitive Behavioral Therapy for Chronic Pelvic Pain: What Is It and Does It Work? J Urol. 2024;211:539-550. Natarajan J, Ahmed T, Patil S, et al. Pain and functionality improved when underlying neuromuscular dysfunction addressed in chronic pelvic pain patients. Neurourol Urodyn. 2021;40:1609-1615. Spruijt MA, Klerkx WM, Kelder JC, Kluivers KB, Kerkhof MH. The efficacy of botulinum toxin a injections in pelvic floor muscles in chronic pelvic pain patients: a systematic review and meta-analysis. Int Urogynecol J. 2022;33(11):2951-2961. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 02 Jan, 2026 Read the published version in International Urology and Nephrology → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8045403","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":546595585,"identity":"fd570e25-b38b-41ef-8737-d99f0a104b19","order_by":0,"name":"Wan-Ru Yu","email":"","orcid":"","institution":"Buddhist Tzu Chi General Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University","correspondingAuthor":false,"prefix":"","firstName":"Wan-Ru","middleName":"","lastName":"Yu","suffix":""},{"id":546595590,"identity":"c1b0448b-22f2-4102-b2ed-93061d2cff4a","order_by":1,"name":"Jia-Fong Jhang","email":"","orcid":"","institution":"Buddhist Tzu Chi General Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University","correspondingAuthor":false,"prefix":"","firstName":"Jia-Fong","middleName":"","lastName":"Jhang","suffix":""},{"id":546595591,"identity":"0ca88941-9c8c-404c-b0e3-98c408063cc7","order_by":2,"name":"Yuan-Hong Jiang","email":"","orcid":"","institution":"Buddhist Tzu Chi General Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University","correspondingAuthor":false,"prefix":"","firstName":"Yuan-Hong","middleName":"","lastName":"Jiang","suffix":""},{"id":546595592,"identity":"e354100d-7fb2-49ea-9ebb-5f00265e112a","order_by":3,"name":"Hann-Chorng 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18:14:38","extension":"xml","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":109112,"visible":true,"origin":"","legend":"","description":"","filename":"4e3a261c05f8429880372fb443f1bad61structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8045403/v1/94441b006d19b69458e57912.xml"},{"id":96603582,"identity":"4702d528-bfad-4711-8ff3-8d2335be4cf3","added_by":"auto","created_at":"2025-11-24 09:10:20","extension":"html","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":115970,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8045403/v1/0cddb170d195c926a0674c61.html"},{"id":96493130,"identity":"36611753-7444-4735-ba15-64a674e9c14e","added_by":"auto","created_at":"2025-11-21 18:14:38","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":28653,"visible":true,"origin":"","legend":"\u003cp\u003eChanges in successful treatment outcomes in patients with multimodal therapy for interstitial cystitis/bladder pain syndrome.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8045403/v1/82dd629b49363e002eccfeb2.png"},{"id":99545187,"identity":"022704b3-076e-4446-bfaf-60dac9bb016b","added_by":"auto","created_at":"2026-01-05 16:01:00","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":745792,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8045403/v1/ff26f4d9-c389-425d-a697-09aa162497c6.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Therapeutic Efficacy of Multimodal Therapy for Patients with Interstitial Cystitis/ Bladder Pain Syndrome Refractory to Previous Bladder Monotherapy","fulltext":[{"header":"Introduction","content":"\u003cp\u003eInterstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic, debilitating condition of unknown etiology, characterized by urinary urgency, frequency, and suprapubic pain associated with bladder filling \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Current oral pharmacological therapies often fail to fully relieve bladder pain or improve bladder capacity. Consequently, pelvic floor-directed interventions, including physical therapy, injections, and nerve blocks, have been explored \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Intravesical hyaluronic acid instillation and intravesical botulinum toxin A (BoNT-A) injection have demonstrated efficacy in alleviating bladder symptoms in patients with IC/BPS \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Autologous platelet-rich plasma (PRP), which is enriched with growth factors and cytokines involved in inflammation modulation and tissue regeneration, has also emerged as a potential therapy \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eFurthermore, low-energy shock wave (LESW) bladder therapy has recently been explored as a regenerative approach for IC/BPS \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. However, neither conventional nor novel therapies have been able to deliver durable treatment outcomes \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. Psychological comorbidities such as anxiety and depression are frequently observed in patients with IC/BPS \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Many patients further report pelvic organ discomfort and a variety of systemic complaints, including gastroesophageal reflux disease, myofascial pain, insomnia, depression, and anxiety \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Pelvic floor muscle pain (PFMP) and voiding dysfunction, often related to urethral sphincter dysfunction or poor pelvic floor muscle relaxation, are also common \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eMost available treatments provide only partial and temporary symptom relief, likely due to the poorly understood pathophysiology of IC/BPS and its heterogeneous clinical subtypes \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Although bladder-directed monotherapies have limited efficacy, combining bladder- and extra-bladder-targeted therapies may better address the multifactorial mechanisms underlying IC/BPS and achieve more durable outcomes \u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. This clinical study aimed to treat patients with IC/BPS who had not responded to monotherapy by applying intensive multimodal therapy (MMT) over a 3-month period. We hypothesized that MMT, tailored to individual clinical assessments and cystoscopic findings, could offer superior and more sustained efficacy compared with monotherapy.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eThis prospective preliminary clinical study enrolled 31 patients with IC/BPS who had failed bladder monotherapy for at least 3 months. All eligible patients underwent comprehensive evaluation, including assessment of anxiety and depression severity indices, interstitial cystitis symptom index (ICSI), interstitial cystitis problem index (ICPI), bladder pain visual analog scale (VAS; 0\u0026ndash;10, from none to severe pain), bladder capacity, and cystoscopic hydrodistention findings (maximal bladder capacity [MBC] and glomerulation grade under anesthesia). Voiding function was assessed using videourodynamic studies, and pelvic floor examination was performed to identify tender points, pain VAS scores, and overall pelvic floor muscle pain (PFMP) scores. Patients were instructed to complete a 3-day voiding diary documenting daytime and nighttime frequency. The maximal bladder capacity recorded in the diary was defined as the functional bladder capacity (FBC). Clinical symptoms were further evaluated using the O\u0026rsquo;Leary\u0026ndash;Sant Symptom Score (OSS, including ICSI and ICPI) and bladder pain VAS. Additional psychological assessments included the perceived pressure scale (PPS), type D personality scale, interpersonal support evaluation list, Beck Anxiety Inventory, and Beck Depression Inventory.\u003c/p\u003e\u003cp\u003eVideourodynamic study (VUDS) was performed in all patients to evaluate bladder function and exclude bladder outlet obstruction (BOO), neurogenic dysfunction, or normal bladder findings. Patients were excluded if they demonstrated a FBC\u0026thinsp;\u0026gt;\u0026thinsp;350 mL on voiding diary, anatomical BOO during the voiding phase, or a low-compliance contracted bladder. Following VUDS, a potassium chloride solution (0.4 M) was instilled intravesically, and the test was considered positive if the patient reported bladder pain or urgency.\u003c/p\u003e\u003cp\u003eCystoscopic hydrodistention was performed under intravenous anesthesia. Intravesical pressure was maintained at 80 cm H₂O until the bladder was fully distended, at which point MBC was measured. After drainage, the bladder wall was inspected for glomerulation, which was graded as follows: 0\u0026thinsp;=\u0026thinsp;none, 1\u0026thinsp;=\u0026thinsp;present in 1\u0026ndash;2 quadrants, 2\u0026thinsp;=\u0026thinsp;present in 3\u0026ndash;4 quadrants, 3\u0026thinsp;=\u0026thinsp;splotch or rainfall hemorrhage, and 4\u0026thinsp;=\u0026thinsp;cracks or mucosal fissures \u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. Hunner-type IC (HIC) was defined as the presence of Hunner lesions with or without glomerulation, which are typically identifiable during office cystoscopy without anesthesia \u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eFollowing evaluation, patients received individualized bladder- and extra-bladder-targeted therapies according to their symptoms and clinical assessments. Treatment options included anti-inflammatory medications, intravesical hyaluronic acid instillation, intravesical BoNT-A or PRP injection, urethral sphincter BoNT-A injection, PFM BoNT-A injection, LESW, pelvic floor massage for PFMP, and medications for voiding dysfunction, bladder hypersensitivity, or psychological stress. Specific treatment selection was guided by the clinical assessment findings (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSuggested treatment modalities selected based on the clinical assessment results\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eClinical Assessment\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCriteria\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTreatment modality\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1.IC symptom score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eICSI\u0026thinsp;\u0026ge;\u0026thinsp;12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNSAID, analgesic, narcotic drugs for 3 months\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2. Bladder pain VAS score (0\u0026ndash;10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eIntravesical BoNT-A 100U injection x 1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3. Glomerulation after HD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026ge; Grade 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eIntravesical PRP injections Q1M x 4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4. Glomerulation after HD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAny grade\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eBladder instillation of heparin, Hyaluronic acid every 1\u0026ndash;2 weeks\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5. Presence of Hunner\u0026rsquo;s lesion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eElectrofulguration or laser ablation of Hunner\u0026rsquo;s lesions, triamcinolone injection\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e6. Pelvic floor focal tenderness\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eVAS\u0026thinsp;\u0026ge;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePFM BoNT-A 100U local injection x 1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e7. Pelvic floor muscle tenderness\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAny grade\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLESW and PFM physiotherapy every 1 week\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e8. Urethral sphincter dysfunction\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eUrethral sphincter BoNT-A 100U injection x 1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e9. Anxiety and depression\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBAI\u0026thinsp;\u0026ge;\u0026thinsp;18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eOral antianxiety or antidepressant medication\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e10. Bladder hypersensitivity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMedication for bladder hypersensitivity, intravesical triamcinolone injection\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e11. Voiding dysfunction\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAlpha-blocker, baclofen\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e12. Hunner\u0026rsquo;s lesion with virus infection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eElevated EB title\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAntiviral agent, Valacyclovir for 3 months\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003eIC: interstitial cystitis, ICSI: interstitial cystitis symptom index; NSAID: non-steroid anti-inflammatory drugs, HD: cystoscopic hydrodistention; BoNT-A: botulinum toxin A; HA: hyaluronic acid; LESW: low energy shock wave; PRP: platelet-rich plasma, PFM: pelvic floor muscle; VAS: visual analog scale for pain; BAI: Beck\u0026rsquo;s anxiety index\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe primary endpoint was the change in OSS from baseline to 3 months after the first injection treatment. Secondary endpoints included bladder pain VAS, daytime frequency, nocturia episodes, FBC from the 3-day voiding diary, Qmax, voided volume, PVR volume, and global response assessment (GRA). Cystoscopic hydrodistention was performed at baseline and again 3 months after treatment initiation. Treatment outcomes were evaluated using the GRA scale ranging from \u0026minus;\u0026thinsp;3 to +\u0026thinsp;3. Patients achieving a GRA of 2 or 3 after MMT were considered treatment successes; all others were classified as failures \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eFollow-up continued for up to one year after MMT completion, or until symptom relapse requiring further bladder treatment. Success rates were assessed at 3, 6, 9, and 12 months after the first treatment day. Adverse events were also recorded, including urinary tract infection (UTI), acute urinary retention, high PVR (\u0026gt;\u0026thinsp;250 mL), dysuria, and micturition pain. This clinical study was approved by the Institutional Review Board and Ethics Committee of the hospital (IRB: 113-023-A, dated December/05/2024). All participants were informed of the study rationale, and written consent was obtained.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eContinuous variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, while categorical variables were presented as counts and percentages. Differences in clinical data between the successful and failed subgroups, as well as changes in variables after MMT, were analyzed using one-way analysis of variance. A \u003cem\u003ep\u003c/em\u003e-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. Statistical analyses were performed using Statistical Package for the Social Sciences, version 20.0 (IBM Corp., Armonk, NY, USA).\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eAmong the 31 patients who completed MMT, 28 were women and 3 were men. HIC was identified in 1 patient, while 30 had NHIC. All had previously received intravesical BoNT-A, PRP, or LESW therapy without success. The specific bladder and extra-bladder therapies included in MMT are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. At 3 months, treatment success was achieved in 7/8 patients (87.5%) who received intravesical BoNT-A, 10/14 (71.4%) who underwent PFM BoNT-A injection for PFMP, and 13/20 (65.0%) who received PFM massage. Overall, 18/31 patients (58.1%) reported successful outcomes at 3 months, including 10 with GRA\u0026thinsp;=\u0026thinsp;2 and 8 with GRA\u0026thinsp;=\u0026thinsp;3. Of the remaining 13 patients, 9 had GRA\u0026thinsp;=\u0026thinsp;1 and 4 had GRA\u0026thinsp;=\u0026thinsp;0.\u003c/p\u003e\u003cp\u003eComparison of baseline clinical symptoms, cystoscopic findings, 3-day voiding diaries, PFM examinations, and VUDS results revealed no significant differences between the successful and failed subgroups. Following MMT, both groups demonstrated significant improvement in ICSI, ICPI, and glomerulation grade. However, significant reductions in bladder pain VAS, PPS, and daytime frequency episodes were observed only in the successful subgroup \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e Notably, as glomerulation grade decreased, MBC significantly increased in the failed subgroup.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSymptom scores, cystoscopic findings, and voiding diary records at baseline and 3 months after multimodal therapy in patients with successful and failed treatment outcomes.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTime\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTotal patients (n\u0026thinsp;=\u0026thinsp;31)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eFailure (GRA\u0026thinsp;=\u0026thinsp;0,1)\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;13)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eSuccessful (GRA\u0026thinsp;=\u0026thinsp;2,3)\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;18)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e47.1\u0026thinsp;\u0026plusmn;\u0026thinsp;15.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e57.9\u0026thinsp;\u0026plusmn;\u0026thinsp;9.27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.039\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eICSI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e13.7\u0026thinsp;\u0026plusmn;\u0026thinsp;3.68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e13.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e13.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.728\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e8.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.35*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e10.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.52*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e7.94\u0026thinsp;\u0026plusmn;\u0026thinsp;2.96*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.059\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eICPI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e12.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e12.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.63\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e12.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.579\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e8.52\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e10.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.93*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e7.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.31*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.004\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eVAS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e5.94\u0026thinsp;\u0026plusmn;\u0026thinsp;2.39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e5.77\u0026thinsp;\u0026plusmn;\u0026thinsp;2.39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e6.06\u0026thinsp;\u0026plusmn;\u0026thinsp;2.46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.748\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e3.61\u0026thinsp;\u0026plusmn;\u0026thinsp;2.29*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e4.85\u0026thinsp;\u0026plusmn;\u0026thinsp;2.51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e2.72\u0026thinsp;\u0026plusmn;\u0026thinsp;1.67*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.008\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003ePPS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e17.9\u0026thinsp;\u0026plusmn;\u0026thinsp;7 .39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e19.9\u0026thinsp;\u0026plusmn;\u0026thinsp;8.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e16.5\u0026thinsp;\u0026plusmn;\u0026thinsp;6.72\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.219\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e15.3\u0026thinsp;\u0026plusmn;\u0026thinsp;6.69*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e18.1\u0026thinsp;\u0026plusmn;\u0026thinsp;6.49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e13.3\u0026thinsp;\u0026plusmn;\u0026thinsp;6.27*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.050\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eDS14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e23.2\u0026thinsp;\u0026plusmn;\u0026thinsp;11.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e23.5\u0026thinsp;\u0026plusmn;\u0026thinsp;11.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e22.9\u0026thinsp;\u0026plusmn;\u0026thinsp;11.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.886\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e23.8\u0026thinsp;\u0026plusmn;\u0026thinsp;9.88\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e27.4\u0026thinsp;\u0026plusmn;\u0026thinsp;10.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e21.2\u0026thinsp;\u0026plusmn;\u0026thinsp;9.21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.087\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eISEL-16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e24.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.81\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e25.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e23.7\u0026thinsp;\u0026plusmn;\u0026thinsp;5.71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.491\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e25.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e23.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e26.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.064\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eBAI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e13.8\u0026thinsp;\u0026plusmn;\u0026thinsp;11.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e14.4\u0026thinsp;\u0026plusmn;\u0026thinsp;14.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e13.4\u0026thinsp;\u0026plusmn;\u0026thinsp;9.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.824\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e14.4\u0026thinsp;\u0026plusmn;\u0026thinsp;11.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e17.9\u0026thinsp;\u0026plusmn;\u0026thinsp;14.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e11.9\u0026thinsp;\u0026plusmn;\u0026thinsp;8.99\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.200\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eBDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e15.0\u0026thinsp;\u0026plusmn;\u0026thinsp;12.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e18.4\u0026thinsp;\u0026plusmn;\u0026thinsp;15.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e12.6\u0026thinsp;\u0026plusmn;\u0026thinsp;9.65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.214\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e13.0\u0026thinsp;\u0026plusmn;\u0026thinsp;10.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e16.5\u0026thinsp;\u0026plusmn;\u0026thinsp;11.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e10.4\u0026thinsp;\u0026plusmn;\u0026thinsp;9.48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.112\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eMBC (ml)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e782\u0026thinsp;\u0026plusmn;\u0026thinsp;177\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e715\u0026thinsp;\u0026plusmn;\u0026thinsp;191\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e831\u0026thinsp;\u0026plusmn;\u0026thinsp;154\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.073\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e887\u0026thinsp;\u0026plusmn;\u0026thinsp;160*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e854\u0026thinsp;\u0026plusmn;\u0026thinsp;195*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e908\u0026thinsp;\u0026plusmn;\u0026thinsp;133\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.372\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eGlomerulation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e1.87\u0026thinsp;\u0026plusmn;\u0026thinsp;0.76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e2.15\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e1.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.77\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.079\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e1.06\u0026thinsp;\u0026plusmn;\u0026thinsp;0.85*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e1.46\u0026thinsp;\u0026plusmn;\u0026thinsp;0.78*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e0.78\u0026thinsp;\u0026plusmn;\u0026thinsp;0.81*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.025\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eFrequency\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e12.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.93\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e13.7\u0026thinsp;\u0026plusmn;\u0026thinsp;6.48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e11.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.295\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e11.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.34*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e13.5\u0026thinsp;\u0026plusmn;\u0026thinsp;5.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e9.73\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.015\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eNocturia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e2.24\u0026thinsp;\u0026plusmn;\u0026thinsp;1.43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e2.56\u0026thinsp;\u0026plusmn;\u0026thinsp;1.85\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.290\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e2.19\u0026thinsp;\u0026plusmn;\u0026thinsp;1.34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e2.75\u0026thinsp;\u0026plusmn;\u0026thinsp;1.69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e1.79\u0026thinsp;\u0026plusmn;\u0026thinsp;0.85\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.046\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eFBC (ml)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e291\u0026thinsp;\u0026plusmn;\u0026thinsp;108\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e292\u0026thinsp;\u0026plusmn;\u0026thinsp;133\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e291\u0026thinsp;\u0026plusmn;\u0026thinsp;89.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.981\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e267\u0026thinsp;\u0026plusmn;\u0026thinsp;103\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e235\u0026thinsp;\u0026plusmn;\u0026thinsp;93.6*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e291\u0026thinsp;\u0026plusmn;\u0026thinsp;105\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.127\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePFM most tendered VAS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e5.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e4.73\u0026thinsp;\u0026plusmn;\u0026thinsp;3.74\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e5.18\u0026thinsp;\u0026plusmn;\u0026thinsp;2.94\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.726\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e3.46\u0026thinsp;\u0026plusmn;\u0026thinsp;3.13*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e4.73\u0026thinsp;\u0026plusmn;\u0026thinsp;3.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e2.65\u0026thinsp;\u0026plusmn;\u0026thinsp;2.69*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.086\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePFMP VAS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e2.18\u0026thinsp;\u0026plusmn;\u0026thinsp;0.94\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e2\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e2.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.92\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.432\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e1.71\u0026thinsp;\u0026plusmn;\u0026thinsp;0.85*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e2.09\u0026thinsp;\u0026plusmn;\u0026thinsp;0.94\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e1.47\u0026thinsp;\u0026plusmn;\u0026thinsp;0.72*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.059\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePFMP points\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e2.61\u0026thinsp;\u0026plusmn;\u0026thinsp;2.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e2.45\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e2.71\u0026thinsp;\u0026plusmn;\u0026thinsp;2.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.779\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e1.46\u0026thinsp;\u0026plusmn;\u0026thinsp;1.53*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e1.82\u0026thinsp;\u0026plusmn;\u0026thinsp;1.66\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e1.24\u0026thinsp;\u0026plusmn;\u0026thinsp;1.44*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.333\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePdet (cmH2O)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e19.4\u0026thinsp;\u0026plusmn;\u0026thinsp;10.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e21.5\u0026thinsp;\u0026plusmn;\u0026thinsp;8.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e17.6\u0026thinsp;\u0026plusmn;\u0026thinsp;12.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.381\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e20.9\u0026thinsp;\u0026plusmn;\u0026thinsp;8.84\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e19.7\u0026thinsp;\u0026plusmn;\u0026thinsp;6.57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e22\u0026thinsp;\u0026plusmn;\u0026thinsp;10.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.372\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eQmax (ml/s)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e10.3\u0026thinsp;\u0026plusmn;\u0026thinsp;6.44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e8.46\u0026thinsp;\u0026plusmn;\u0026thinsp;3.64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e11.6\u0026thinsp;\u0026plusmn;\u0026thinsp;7.71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.183\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e12.5\u0026thinsp;\u0026plusmn;\u0026thinsp;6.93\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e8.85\u0026thinsp;\u0026plusmn;\u0026thinsp;4.34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e15.1\u0026thinsp;\u0026plusmn;\u0026thinsp;7.37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.011\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVolume (ml)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e188\u0026thinsp;\u0026plusmn;\u0026thinsp;101\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e166\u0026thinsp;\u0026plusmn;\u0026thinsp;69.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e204\u0026thinsp;\u0026plusmn;\u0026thinsp;118\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.315\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e204\u0026thinsp;\u0026plusmn;\u0026thinsp;98.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e150\u0026thinsp;\u0026plusmn;\u0026thinsp;78.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e243\u0026thinsp;\u0026plusmn;\u0026thinsp;94.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.007\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePVR (ml)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e37.1\u0026thinsp;\u0026plusmn;\u0026thinsp;79.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e57.3\u0026thinsp;\u0026plusmn;\u0026thinsp;115\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e22.4\u0026thinsp;\u0026plusmn;\u0026thinsp;34.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.233\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e30.6\u0026thinsp;\u0026plusmn;\u0026thinsp;43.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e36.2\u0026thinsp;\u0026plusmn;\u0026thinsp;45.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e26.6\u0026thinsp;\u0026plusmn;\u0026thinsp;43.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.554\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFSF (ml)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e126\u0026thinsp;\u0026plusmn;\u0026thinsp;37.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e124\u0026thinsp;\u0026plusmn;\u0026thinsp;33.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e127\u0026thinsp;\u0026plusmn;\u0026thinsp;40.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.832\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e123\u0026thinsp;\u0026plusmn;\u0026thinsp;54.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e98\u0026thinsp;\u0026plusmn;\u0026thinsp;51.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e140\u0026thinsp;\u0026plusmn;\u0026thinsp;50.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.030\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFS (ml)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e211\u0026thinsp;\u0026plusmn;\u0026thinsp;63.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e207\u0026thinsp;\u0026plusmn;\u0026thinsp;67.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e214\u0026thinsp;\u0026plusmn;\u0026thinsp;62.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.762\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e199\u0026thinsp;\u0026plusmn;\u0026thinsp;75.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e156\u0026thinsp;\u0026plusmn;\u0026thinsp;64.2*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e229\u0026thinsp;\u0026plusmn;\u0026thinsp;69.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.006\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUS (ml)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e235\u0026thinsp;\u0026plusmn;\u0026thinsp;81.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e229\u0026thinsp;\u0026plusmn;\u0026thinsp;80.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e239\u0026thinsp;\u0026plusmn;\u0026thinsp;84.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.741\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e220\u0026thinsp;\u0026plusmn;\u0026thinsp;78.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e168\u0026thinsp;\u0026plusmn;\u0026thinsp;53.0*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e256\u0026thinsp;\u0026plusmn;\u0026thinsp;73.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCompliance (ml/cmH2O)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e74.8\u0026thinsp;\u0026plusmn;\u0026thinsp;86.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e38.8\u0026thinsp;\u0026plusmn;\u0026thinsp;14.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e101\u0026thinsp;\u0026plusmn;\u0026thinsp;10 6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.025\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e71.0\u0026thinsp;\u0026plusmn;\u0026thinsp;60.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e58.5\u0026thinsp;\u0026plusmn;\u0026thinsp;45.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e80.0\u0026thinsp;\u0026plusmn;\u0026thinsp;69.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.335\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBCI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e74.0\u0026thinsp;\u0026plusmn;\u0026thinsp;32.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e65.6\u0026thinsp;\u0026plusmn;\u0026thinsp;23.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e81.1\u0026thinsp;\u0026plusmn;\u0026thinsp;38.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.255\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e77.2\u0026thinsp;\u0026plusmn;\u0026thinsp;31.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e62.5\u0026thinsp;\u0026plusmn;\u0026thinsp;25.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e90.8\u0026thinsp;\u0026plusmn;\u0026thinsp;30.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.034\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCBC (ml)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e225\u0026thinsp;\u0026plusmn;\u0026thinsp;102\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e224\u0026thinsp;\u0026plusmn;\u0026thinsp;81.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e226\u0026thinsp;\u0026plusmn;\u0026thinsp;117\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.946\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e235\u0026thinsp;\u0026plusmn;\u0026thinsp;88.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e186\u0026thinsp;\u0026plusmn;\u0026thinsp;65.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e269\u0026thinsp;\u0026plusmn;\u0026thinsp;88.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.008\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBOOI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e-2.46\u0026thinsp;\u0026plusmn;\u0026thinsp;18.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e3.82\u0026thinsp;\u0026plusmn;\u0026thinsp;6.85\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e-7.77\u0026thinsp;\u0026plusmn;\u0026thinsp;24.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.119\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e-1.61\u0026thinsp;\u0026plusmn;\u0026thinsp;15.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e2.64\u0026thinsp;\u0026plusmn;\u0026thinsp;9.86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e-5.5\u0026thinsp;\u0026plusmn;\u0026thinsp;19.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.372\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003e* P\u0026thinsp;\u0026lt;\u0026thinsp;0.05, GRA: global response assessment, ICSI: interstitial cystitis symptom index, ICPI: interstitial cystitis problem index, VAS: visual analog scale of pain, PPS: perceived pressure scale, DS14: type D personality scale, ISEL16: interpersonal support evaluation list, BAI: Beck\u0026rsquo;s anxiety index, BDI: Beck\u0026rsquo;s depression index, MBC: maximal bladder capacity, FBC: functional bladder capacity, VAS: visual analog scale of pain, PFMP: pelvic floor muscle pain, Pdet: detrusor pressure, Qmax: maximum flow rate, PVR: post-void residual, FSF: first sensation of filling, FS: fullness sensation, US: urge sensation, BCI: bladder contractility index, CBC: cystometric bladder capacity, BOOI: bladder outlet obstruction index.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003ePFMP parameters\u0026mdash;including the pain score of the most tender point, overall PFMP VAS, and the number of PFMP sites\u0026mdash;showed significant improvement in the successful subgroup but not in the failed subgroup. In contrast, VUDS parameters did not demonstrate significant changes in either group. Patients with failed outcomes were noted to have decreased bladder fullness and urgency sensation volumes.\u003c/p\u003e\u003cp\u003eFollowing the primary endpoint, the success rate of MMT was 51.6% (16/31) at 6 months, rising to 67.7% (21/31) at 9 months and 73.1% (23/31) at 12 months. Notably, five patients who had initially failed treatment at 3 months showed gradual improvement during follow-up. By 12 months after the first treatment, only 8 patients (26.9%) required additional bladder therapy.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study demonstrated that 58.1% of patients with IC/BPS who had failed prior bladder therapies achieved successful outcomes at 3 months following MMT, based on clinical assessments and tailored combinations of bladder and extra-bladder treatments. The success rate further increased to 73.1% at 1 year. Among the treatment modalities, intravesical BoNT-A injection and PFM therapy yielded the highest rates of success. Patients with favorable outcomes also experienced significant reductions in PFM pain and tender points. These findings suggest that IC/BPS may arise from heterogeneous underlying mechanisms, making monotherapy insufficient for many patients, while a multimodal therapeutic approach can provide more durable benefits.\u003c/p\u003e\u003cp\u003eVarious pathogenic mechanisms of IC/BPS have been proposed from clinical and animal studies \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. These include bladder inflammation with urothelial injury, suburothelial inflammation, pan-cystitis characterized by chronic inflammatory infiltration of the suburothelium and detrusor muscle, chronic scarring within the bladder wall, and central nervous system involvement with heightened inflammatory activity in the dorsal root ganglia and sacral spinal cord segments \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Considering this multifactorial pathogenesis, identifying a single initiating factor or optimal treatment target remains challenging. Therapeutic strategies are therefore often guided by the nature and severity of bladder and nervous system pathology \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. In line with this, the revised AUA guidelines for IC/BPS have abandoned tiered treatment recommendations and instead advocate MMT to address both bladder-specific and systemic symptoms simultaneously, thereby offering the potential for more durable and effective outcomes \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eManagement of IC/BPS should be tailored according to subtype, with different approaches for HIC and NHIC. For patients diagnosed with HIC, the first-line therapy is cystoscopic ablation of Hunner\u0026rsquo;s lesions, typically using electrofulguration or laser ablation \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. In this study, we additionally applied PRP combined with triamcinolone to the lesion sites after fulguration, a strategy previously reported to yield encouraging preliminary results \u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. Patients often experienced rapid pain relief and favorable re-epithelialization at treated sites. Notably, Epstein\u0026ndash;Barr virus has been detected in the bladder walls of patients with HIC \u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e, leading to exploration of adjunctive antiviral therapy with low-dose valacyclovir following lesion ablation \u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. Although only one patient with HIC was enrolled in this study, she achieved a successful treatment outcome.\u003c/p\u003e\u003cp\u003eEarlier guidelines stratified treatment according to symptom severity and the invasiveness of bladder-directed interventions \u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. Currently available oral pharmacotherapies\u0026mdash;including nonsteroidal anti-inflammatory drugs, corticosteroids, antihistamines, anticholinergics, β3-adrenoceptor agonists, cyclosporine, and analgesics\u0026mdash;have shown only limited efficacy in relieving symptoms or eradicating bladder pain in IC/BPS \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Intravesical therapies such as glycosaminoglycan (GAG) instillations and BoNT-A injections can provide short-term benefit, but long-term durability remains limited for most patients \u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. Although intravesical BoNT-A injection is listed in the AUA guidelines, it is generally considered secondary to GAG supplementation therapy \u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. In practice, BoNT-A injections are used to mitigate chronic inflammation and suppress inflammation-induced apoptotic pathways \u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. Clinical studies have demonstrated that intravesical BoNT-A reduces bladder pain and IC symptom scores while increasing FBC \u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. Immunohistochemical analyses further support these findings, showing reduced apoptotic activity and mast cell infiltration, alongside increased Ki-67 and E-cadherin expression. Moreover, repeated intravesical BoNT-A injections at 6-month intervals have been associated with reductions in glomerulation severity during cystoscopic hydrodistention \u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eIn this study, we observed that MMT incorporating intravesical BoNT-A injection achieved a high success rate in patients with elevated bladder pain VAS, while PFM BoNT-A injection was particularly effective in patients with PFMP. These findings suggest that BoNT-A injections can effectively suppress chronic bladder inflammation and provide pain relief both in the bladder and pelvic floor muscles. Chronic inflammation-induced sensory hyper-innervation is recognized as a key pathophysiological mechanism underlying IC/BPS symptoms \u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e,\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. The therapeutic effect of BoNT-A appears to be superior to other novel therapies such as PRP injection or LESW bladder therapy.\u003c/p\u003e\u003cp\u003eRegenerative strategies, including intravesical PRP therapy and LESW, aim to reduce chronic inflammation and enhance urothelial proliferation and maturation. However, their efficacy remains limited, as persistent inflammation often hampers durable outcomes \u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. These bladder-focused treatments address selected aspects of IC/BPS pathophysiology but are insufficient to fully resolve its multifactorial nature, particularly in refractory cases. Nevertheless, adjunctive use of PRP in patients with high-grade glomerulation, and LESW in those with PFM tenderness, demonstrated additional benefit, as reflected by reductions in glomerulation grade and PFMP severity in the failed subgroup.\u003c/p\u003e\u003cp\u003eImportantly, our results show that the success rate of MMT increased from 3 months to 9 and 12 months, suggesting that bladder condition progressively improves over time with adequate anti-inflammatory and regenerative therapy. Although there was a slight decline in response at 6 months, this may be due to unresolved bladder inflammation following initial intravesical injection therapies. With continued treatment, inflammation subsides, urothelial integrity is restored, and barrier function improves, as evidenced by the reduction in glomerulation grade during follow-up cystoscopic hydrodistention.\u003c/p\u003e\u003cp\u003eAnxiety, depression, and psychological stress are commonly associated with IC/BPS and can exacerbate symptoms by disrupting urothelial integrity and provoking symptom flares \u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. Stress is strongly correlated with symptom severity, particularly in patients who are refractory to conventional therapies. Mechanistically, stress may compromise the bladder\u0026rsquo;s mucosal barrier, increase urothelial permeability, thereby inducing irritation and pain. Previous studies have shown that patients with severe IC/BPS often present with higher levels of anxiety and depression \u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. Incorporating psychiatric consultation alongside bladder-targeted therapies has been reported to reduce symptom indices; however, current evidence has not yet demonstrated the superiority of multimodal approaches that include psychiatric support or PFM therapy over monotherapy in IC/BPS management \u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eBeyond bladder pathology, extra-bladder conditions such as PFM dysfunction, fasciitis, visceral inflammation, irritable bowel syndrome, endometriosis, and other pelvic organ disorders can provoke bladder pain and irritative symptoms via cross-organ communication within the central nervous system \u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. Myofascial pain syndrome is particularly common among patients with nonbladder-centric IC/BPS. On physical examination, many such patients demonstrate PFMP with palpable trigger points \u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. In these cases, bladder-directed therapies alone are typically insufficient, as the primary pain source originates from the PFM. BoNT-A injections at PFM tender points have been shown to effectively alleviate PFMP in patients with IC/BPS accompanied by pelvic floor hypertonicity \u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. In our study, extra-bladder therapies were added for patients with PFM tenderness. Interventions such as PFM BoNT-A injections and PFM physiotherapy, with or without LESW therapy, significantly reduced PFMP severity and tender points, further supporting the therapeutic value of targeting PFMP in this patient population.\u003c/p\u003e\u003cp\u003eThis study is the first clinical investigation to demonstrate the efficacy of MMT in treating patients with IC/BPS who had failed prior bladder-directed therapies. The rationale for MMT is grounded in the complex and multifactorial pathophysiology of IC/BPS, which often necessitates the integration of multiple therapeutic strategies. Depending on the predominant clinical features and concomitant treatment for bladder pain, bladder hypersensitivity, urothelial dysfunction, PFMP, psychological distress, and coexisting organ dysfunction, MMT can provide a satisfactory outcome. Although these interventions vary in mechanism and target distinct pathophysiological pathways, their combined use enables durable and meaningful clinical improvements in patients with IC/BPS who do not respond to monotherapy.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eA precision-driven diagnostic approach that stratifies patients with IC/BPS into clinical subtypes based on distinct pathophysiological profiles and symptom characteristics may facilitate more tailored and effective management. MMT should incorporate a combination of bladder-directed and extra-bladder interventions to address the heterogeneous mechanisms underlying the disease. Depending on individual presentation, patients may benefit from either single therapies or concurrent treatment combinations to optimize symptom relief and long-term outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eIRB:\u003c/strong\u003e IRB code: 113-023-A, the study was approved by the Research Ethics Committee of Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation on December/05/2024.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding statement:\u003c/strong\u003e This study was funded by the Buddhist Tzu Chi Medical Foundation, grant TCMF-MP-114-02-01\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHayes B, Namugosa M, Evans RJ, et al. 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The efficacy of botulinum toxin a injections in pelvic floor muscles in chronic pelvic pain patients: a systematic review and meta-analysis.\u003cem\u003eInt Urogynecol J. \u003c/em\u003e2022;33(11):2951-2961.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8045403/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8045403/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003eInterstitial cystitis/painful bladder syndrome (IC/BPS) is a debilitating chronic condition, and current treatments rarely achieve complete symptom relief. This study evaluated the efficacy of intensive multimodal therapy (MMT) for IC/BPS based on individualized clinical assessments within a 3-month period.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThirty-one patients with IC/BPS who had failed prior monotherapy were enrolled. Following comprehensive evaluation, patients received tailored MMT, which could include anti-inflammatory medications, intravesical hyaluronic acid instillation, intravesical or urethral botulinum toxin A (BoNT-A) injection, pelvic floor BoNT-A injection, platelet-rich plasma injection, low-energy shockwave therapy, pelvic floor massage for pelvic floor muscle pain (PFMP), and/or medications for anxiety, depression, voiding dysfunction, or bladder hypersensitivity. The primary outcome was assessed at 3 months using the global response assessment (GRA), with a successful response defined as a GRA score of 2 or 3. Patients were followed for up to 1 year.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eOf the 31 patients (28 women, 3 men), 18 (58.1%) reported a successful outcome at 3 months. Successful and unsuccessful subgroups showed significant improvements in symptom scores and glomerulation grade after cystoscopic hydrodistention. However, reductions in pain VAS and daytime frequency were observed only in the successful subgroup. Similarly, PFMP parameters improved significantly in the successful subgroup but not in the failed subgroup. Sustained therapeutic effects were observed in 21 patients (67.7%) at 9 months and in 23 patients (74.2%) at 1 year after MMT.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eMultimodal bladder therapy, incorporating bladder- and extra-bladder\u0026ndash;targeted approaches, yields satisfactory outcomes in patients with IC/BPS unresponsive to prior monotherapy.\u003c/p\u003e","manuscriptTitle":"Therapeutic Efficacy of Multimodal Therapy for Patients with Interstitial Cystitis/ Bladder Pain Syndrome Refractory to Previous Bladder Monotherapy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-21 18:14:33","doi":"10.21203/rs.3.rs-8045403/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"85f2626c-d1af-430b-bca5-826c0bbc52c6","owner":[],"postedDate":"November 21st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-05T15:58:57+00:00","versionOfRecord":{"articleIdentity":"rs-8045403","link":"https://doi.org/10.1007/s11255-025-04981-6","journal":{"identity":"international-urology-and-nephrology","isVorOnly":false,"title":"International Urology and Nephrology"},"publishedOn":"2026-01-02 15:57:01","publishedOnDateReadable":"January 2nd, 2026"},"versionCreatedAt":"2025-11-21 18:14:33","video":"","vorDoi":"10.1007/s11255-025-04981-6","vorDoiUrl":"https://doi.org/10.1007/s11255-025-04981-6","workflowStages":[]},"version":"v1","identity":"rs-8045403","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8045403","identity":"rs-8045403","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}